Intro

Over the course of many years, stem cell therapies have been developed for regenerative medicine, but one of the main challenges remains how they should be delivered. When delivering any treatment method, getting as close to the affected area and using as targeted of a therapy as possible is one of the best ways to garner results. When targeted therapies are used, the drug or therapy becomes increasingly accessible to the tissues that are targeted (Levin, et.al), making the treatment that much more effective since the cells are able to gain the most benefit.

Targeted stem cell delivery offers unique advantages related to the particular nature of stem cells, which function as blank slates, meaning they can take on the form and function as the type of cell they are needed to be (Zakrzewski, et.al). Furthermore, they are able to differentiate into a multitude of cell types, depending on the regenerative signals that are expressed by the surrounding cells or tissues. Stem cell therapies have long been looked into in terms of various tissues, and some examples of these are ocular, cardiovascular, and osseous tissues, to facilitate regrowth or regeneration (Zakrzewski, et.al).

Some of the advantages of the injection procedures compared to open-wound surgery include that these are minimally invasive which leads to a less traumatic treatment which also minimizes the post-procedure complications for the recipient due to there not being large open wounds.

In terms of delivery methods, stem cells have been injected in vehicle media, hydrogels, and in microspheres/microtissues. Injection of stem cells in a vehicle medium is the most direct method, but cells may sustain damage. However, by immobilizing them into a biomaterial, such as a hydrogel or microsphere/microtissue, the stem cells are protected in a more complex environment during the implantation process. (Ashammakhi, et.al)

Injectable Stem Cells

The basis of implantation of stem cells in a minimally invasive manner is injection. This is one of the best ways to reduce the invasiveness to deliver the cells to their target. Stem cells suspensions can be delivered directly, through a syringe and needle. This, however, can pose a threat to the cells themselves as there is nothing but a saline solution protecting them from the pressure induced by the needle during the implantation process and causing damage to the cell walls. If this happens, a portion of the cells delivered may not be viable and therefore decrease the efficacy of the treatment (Ashammakhi, et.al). Notwithstanding, the size of the needle can be altered to prevent this occurrence. An optimal size needle (16-22 gauge) is used so that the stress on the cells is minimized. Large needles, on the other hand, could cause sediment and therefore affect the viability and homogeneity of dispersion of the cells as well (Ashammakhi, et.al).

One application of direct injection is in osteoarthritic patients, who need the treatment to help their deteriorating joints. Freitag, et. al. (2019) performed a clinical trial in which a suspension of stem cells in a saline solution were injected into the knee joints of the experimental groups (n=10 individuals over 18 years old with symptomatic knee osteoarthritis received 1 injection of 100 × 10^6 ADMSCs in saline, n=10 individuals received 2 injections of 100 × 10^6 ADMSCs in saline at t=0 and 6 months). The control group (n=10 individuals over 18 years old with symptomatic knee osteoarthritis) received conservative treatment for osteoarthritis. This paper demonstrated that when ADMSCs were injected, they were largely effective in both pain relief (NPRS improvement of 69% from starting point to 12 mo. in both groups) and functional

improvement of the joint for the patients treated (KOOS scale on 1 and 2 injections with subscores for symptom improvement, activities of daily living, sport and recreation, and quality of life both significantly improved when compared to the control), as quantified with numeric pain rating scale, knee injury and osteoarthritis outcome score, and the western Ontario and McMaster universities osteoarthritis index, and MRI imaging (Freitag et. al).

Injectable Hydrogels

Unlike direct injection, a hydrogel provides a material for the stem cells to be embedded and protected from the external environment. This method allows to retain the cells in the site of implantation for a longer period of time, compared to the direct injection of stem cells in a buffer medium. In this latter case, the injected cells are often dispersed in the surrounding aqueous milieu. However, the biomaterial component adds a level of complexity to the system, and extensive characterization of the biomaterials in vitro and in vivo is needed to ensure biocompatibility, and adequate degradation kinetics in order to prevent any immune response or rejection of therapeutics.

One of the hallmarks of a hydrogel is that it can mimic a cell’s natural environment, therefore leading to a healthier, more viable sample or stem cells (Ma Y, et.al). By providing this type of environment for the cells, they are able to proliferate and act in the intended method, due to the biophysical cues provided by the hydrogel. Different types of hydrogels can promote different behaviors, such as adhesion, migration, proliferation, or differentiation, depending on the gel’s characteristics, including degradability, shape memory, hydrophilicity/hydrophobicity (Ma J, et.al).

Additionally, hydrogels can be either natural (taken from the extracellular matrix) or synthetic (artificially manufactured with chemical materials). In general, if a very specific chemical composition is needed or a durable and stable gel is required for the tissue engineering application, a synthetic gel might be best, but if a quickly degrading, non-immune-inducing method is needed, a natural gel may work better (Choe, et.al).

Below is a table organizing various applications of minimally invasive stem cell delivery by way of hydrogels.

Injectable 3D Scaffold-Free Microtissues

Continuing on, in this methodology of delivery, the cells are cultured in the lab into a 3D spheroid or piece of microtissue, without the use of a supporting biomaterial. There are numerous benefits to this practice in the context of cell protection and proliferation as well. In terms of cell protection, these spheroids/microtissues help greatly in combating damage caused by the pressure induced in the syringe when delivery occurs (Li, et.al). Additionally, these spheroids and microtissues can simulate an in-vivo environment and can be made into different shapes depending on their final location’s needs. This can lead to them being more responsive and productive. In the trials of Li, et. al, 3D microtissues were implanted into mice in a minimally invasive approach, and were trying to deduce whether when the hMSC (human mesenchymal stem cells) would make an impact on necrosis through a mouse limb ischemia model. The results showed that no limb salvage was observed among the control group, but out of those that received the microtissue treatment (density of 10^5 hMSCs), 75% showed salvage, and only 25% resulted in spontaneous limb necrosis (Li, et.al). Moreover, cell sheet technology, which is a type of scaffold-free microtissue, shows promising results. Many times before, when stem cells were just directly injected, the level of cell loss outweighed the benefit of using this method, but with the cell sheet, this problem of cell retention is no longer a problem (Narita et.al). Additionally, because the cell sheets do not involve a scaffold, they do not elicit an immune response, making it safer for the patient. Finally, the work of Yamada, et.al, shows that adipose derived stem cells (ADSCs) show promising results for bone and cartilage regeneration. Due to their rapid regeneration/differentiation rate, they function well for bone and cartilage repair. In this study, the ADSCs were cultured and made into 3D scaffold-free spheroids. They were then implanted (via injection) into rats that had defects in their calvarial bones (Yamada, et. al). Through this study, it was found that the 3D scaffold-free spheroids had lower rates of cell apoptosis compared to ADSC- single cells in both the in-vitro conditions of the laboratory they were manufactured in and in the in-vivo model (for 12 weeks) of the rat. Thus, it was concluded that injectable ADSC-spheroids are a viable option to minimally invasive stem cell delivery for bone and cartilage regeneration (Yamada, et. al).

Conclusion

All together, there are various aspects to delivery of stem cells. Over the course of this review, three important methods of minimally invasive stem cell delivery have been discussed. There are advantages and disadvantages to each. For example, direct injection uses nothing but a saline solution, meaning that it is the most cost-effective way, but it also does not do much in terms of protecting the cells or helping them proliferate; hydrogels can mimic a stem cell’s ideal environment, but deciding between a natural or synthetic hydrogel may prove to be challenging; spheroids and microtissues are the newest method, and are extremely effective since they seamlessly mimic an in-vivo environment, but they have to be grown in a lab first and may not be the most cost-effective. In summary, depending on the need of the research or patient, different methods can be used, but all aspects should be considered to choose the best one.

Citations

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About the author

Rishya Gutti

Rishya is currently a senior at Neuqua Valley High School. She is interested in the biological sciences and is an aspiring medical student. Research programs like RISE (Research, Inquiry Skills & Experimentation) have equipped Rishya with the necessary skills to conduct independent research. She is a fourth degree black belt in Taekwondo and has won several national titles in her age group. Rishya also enjoys volunteering her time to teach mathematics to younger students and to promote mental health awareness through a non-profit organization. In her free time, you will find her reading, working out or watching her favorite tv shows.

The post Minimally Invasive Delivery of Stem Cells for Tissue Regeneration appeared first on Exploratio Journal.

Abstract

Heart attacks, or Myocardial Infarctions (MI), lead to death of tissue due to lack of blood supply to the portion of the organ. Resulting scar tissue does not contract or function as well as healthy muscle tissue. On the other hand, stem cells have shown propensity to be guided into becoming specific cells that can be used to regenerate and repair diseased or damaged tissues in people. This paper will explore the latest research that supports using induced pluripotent stem cells for tissue reparation in cardiovascular disease.

Introduction

Over the past few decades, stem cell therapies have evolved considerably and one of their many potential applications could be to repair the scarring caused by myocardial infarctions. Myocardial Infarction (MI), which is a reduction or blockage of blood flow in the coronary arteries, commonly referred to as heart attack, is one of the leading causes of death in the United States with 805,000 people experiencing one every year (CDC). Unfortunately, out of those 805,000, 12% will die (CDC). Following MI, the inadequate blood flow to the infarcted tissue causes a severe reduction of oxygen and nutrients, leading to cardiomyocyte necrosis (reduced contractility), and therefore compromised heart function. MI does not traditionally have any treatment since once the tissue has necrotized, it can not regain its function. MI’s can only be managed with preventative measures taken to inhibit another incident. Medicines like aspirin and other anti-clotting drugs are used to keep clots from forming and causing another MI (CDC). ACE inhibitors reduce the strain on the heart by lowering blood pressure and this helps to not weaken the damaged tissues any further (NIH). Similarly, Betablockers also reduce the strain on the organ by blocking the release of stress hormones like noradrenaline and adrenaline to keep heart rate constant (NIH). All of these, however, only reduce the risk of a recurrence and do not regenerate the dead tissue, whereas a different form of therapy for the damaged tissue could bring about a brighter prospect. Stem cells can regenerate tissues suitable to one’s own body without having to use a transplant. This makes it less risky when it comes to a patient’s body rejecting the cells. Some varieties are also easily accessible, usable, and effective in their respective needs.

Out of the many varieties of stem cells, induced pluripotent stem cells, are some of the most promising to study. Induced pluripotent stem cells (iPS cells) are derived from somatic cells that are reprogrammed into iPS cells. These cells can then be made to differentiate into whatever tissue cell is needed (Shi et al, 2016). They are also important to observe because of their accessibility and high turnover rate (Krzysztof et al, 2018). In this review, we will focus on two types of stem cells: induced pluripotent stem cells, and their abilities in tissue regeneration in regards to therapies to treat the infarcted myocardium (Yoshida et al, 2017).

Induced Pluripotent Stem cells

Induced Pluripotent Stem Cells (iPSCs) are adult somatic cells that are reprogrammed into a pluripotent state. These cells are adults and unipotent, meaning they are capable of regenerating only their own specific tissue type (Tweedell, 2017). For example, an adult somatic cell in the skin could only generate skin cells. When these cells are reprogrammed into iPSCs, they become pluripotent, and are able to differentiate into any type of tissue with appropriate differentiation factors (Tweedell, 2017).

The use of iPSCs for regenerative medicine bears significant advantages. In fact, the somatic cells generally used for reprogramming are highly accessible and they are already part of the body of the person who needs them. Therefore, there is no risk of rejection when they are implanted for regenerating damaged tissues or organs (Arjmand et al, 2017). One further advantage is that they are not controversial like embryonic stem cells that are isolated from embryos while having similar properties. Generating the iPSCs is completed by taking any healthy adult somatic cells from the body and reverse engineering them into a pluripotent state where they can then differentiate into whatever cell type is needed. How this occurs is that first, the cells organize spatially and then divide into three areas. The middle section, differentiates into the middle portion of the three’s lineage and this activates certain genes.

Cardiovascular Regeneration

As mentioned above, one of the capabilities of iPSCs is tissue regeneration, which is paramount for cardiovascular tissue regeneration. The basic process for cardiovascular tissue engineering consists in isolating somatic cells of the patient or from healthy donors, which are then reprogrammed to iPSCs. Next, the obtained iPSCs are differentiated into the specific cell type that is needed (such as cardiomyocytes, cardiac fibroblasts, or endothelial cells). The differentiated cells must be cultured in the lab to grow, and during this process they can be stimulated with chemical or physical cues to mimic the mechanical properties of the beating heart. The last step is to inject or implant the cells into the patient.

Cardiovascular tissue engineering has shown promising results in vitro and in preclinical in vivo studies. Several groups have used small animal models, including mice and rats model of myocardial infarction to assess the ability of repairing the damaged heart tissue with iPSCs-derived cardiomyocytes. An example of implantation of cardiac engineered tissues in a small animal model is provided by (Tompkins et. al. 2018), that used 3D bioprinted iPSC-derived cardiomyocytes, fibroblasts and endothelial cells to produce 3D patches that were implanted in n=6 infarcted rats.

Additionally, vivo models further demonstrate that this path of study is incredibly promising. The work of Tompkins et. al. describes small animal models where iPSCs are implanted. This article demonstrates how this work is viable in live models as they tested various species of small animals to prove efficacy. Moreover, the same study considered large animal studies and deduced that they too have promising results. More specifically, in swine models, which are known to have extremely similar cardiac structure to that of humans, these studies further the thought that using iPSCs to repair tissues is a viable solution. Kawamura et al. placed a sheet of dermal fibroblast-derived hiPSC-CMs over the infarcted area in an ischemic swine model, which produced improved cardiac performance, angiogenesis (increased number of blood vessels in the infarct), and an attenuated LV remodeling 8-weeks post implantation.

While in the lab, stimuli of stretching and current are used to help the cells mature faster and grow more resilient. This is one place of research that is continuing to challenge researchers, since they do not have years to culture mature cells and there is risk with implanting immature cells regarding their ability to adapt to the heart’s environment. However, it can and has been done, as explained above, which has drawn tremendous attention to this field of pursuit. Moreover, cardiovascular regeneration is one of the newest technologies in repairing damaged tissues in the heart. This breakthrough has made it possible to just regrow healthy and functional tissue instead of needing a transplant since it is already known that once tissue is dead from a myocardial infarction, there is no way to salvage it. As the MI damages the tissue, it makes it impossible for the original tissue to be functional, so inputting fresh, cultivated tissues open up new possibilities in life for the patient after their MI episode.

Drug Screening

During the process of drug screening, various drugs are tested on the cardiac engineered tissues to gauge safety and efficacy of the tested molecules and drugs. One of the commonly tested side effects of newly developed drugs are for drug induced arrhythmias. By testing in-vitro with iPSCs outside of a patient’s body, it is not only more convenient to do so but also safer so as to not involve a live subject (Smith et. al. 2017). Various types of cell models are used, ranging from flat, 2D monolayers to more complex 3D tissues, organ-on-a-chip models show a wide range of functionality. Each of these model types show a range from the least to most complex levels of organization in order to understand how drugs can affect the cardiomyocytes on a basic to fully vascularized level (Smith et. al. 2017 Fig. 1). This is one place of development in the field of iPSCs that would be of great benefit to the scientific community and to the general population as well. If drugs can be screened and tested within a lab without having to use in vivo models until much later in the process, it can be much more ethical and more varieties of medicines that may or may not be viewed as viable could potentially be trialed in this way due to the reduced ethics concerns.

One example of a clinical trial is in the research of Blinova et. al. which shows a personalized drug screen model that highlights how iPSCs derived from 22 healthy subjects can be grown and tested within a dish. Safety and efficacy of two drugs, dofetilide and moxifloxacin (hERG‐blocking and QT prolonging), were tested on iPSCs isolated from the peripheral blood mononuclear cells and differentiated in cardiomyocytes. There were no drug induced arrhythmia-like events observed at the studied drug concentration rate. In vivo model of testing that highlights how tissue can be grown and tested within a dish. In this trial, the researchers tested and analyzed for arrhythmias in the iPSCs. This demonstrates how various environments of the heart can be simulated in the lab and that it is necessary to do so (Blinova et. al. 2019)

Various different types of trials can be used to screen for arrhythmias in a drug screening. One method researchers historically and commonly use is the analysis of hERG channel response which is the standard procedure for in vitro preclinical trials of drug screening. While this is a method commonly used, it is not as accurate as could be desired since false positive results are frequent occurrences (Smith et. al. 2017). This is why iPSC-CMs are making headway in the field of drug screening since they offer a more accurate option. There are various tests researchers can run with in vitro models of iPSCs to represent the function of the heart more fully and effectively. Out of the multitude of options researchers now have with iPSC-CMs as an option, an example presented in the above research is that researchers measure cell contraction to observe the cardiomyocytes’ contractile function (Smith et. al. 2017).

Conclusion

After an episode of myocardial infarction, heart tissue is damaged irreversibly and the prognosis only entails either drug therapeutics or organ transplant. Cardiovascular regeneration is one of the newest technologies in regards to repairing damaged tissues in the heart. With reprogrammed iPSCs , the patient is able to have their healthy cells cultured in a lab and remediate the scarred tissue resulting from an MI episode. Furthermore, progress has also been made in labs to accommodate the new research and to screen drugs to ensure their safety with the cultured tissues when implanted in a person. All together, these breakthroughs have made it possible to regrow healthy and functioning tissue and using iPSCs could make this possibility a reality.

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About the author

Rishya Gutti

Rishya is a junior at Neuqua Valley High School. She is interested in biological sciences and is an aspiring medical student. Research programs like RISE (Research, Inquiry Skills & Experimentation) have equipped Rishya with necessary skills to conduct independent research. She is a third degree black belt in Taekwondo and has won several national titles in her age group. Rishya enjoys volunteering her time to teach mathematics to younger students and to promote mental health awareness through a non-profit organization. In her free time, you will find her reading, working out, or watching her favorite tv shows.

The post Using induced pluripotent stem cells for tissue regeneration in cardiovascular diseases appeared first on Exploratio Journal.

Abstract

The ability of stem cells to self-renew and form different mature cells expands the possibilities of application in cell therapy, such as tissue reorganization in regenerative medicine, drug detection, and treatment of neurodegenerative diseases. In addition to stem cells found in embryos, several adult organs and tissues also have stem cell niches in an undifferentiated state. In the central nervous system of adult mammals, neurogenesis occurs in two areas: the subventricular zone and the dentate gyrus of the hippocampus. The different nervous systems originate from adult neural stem cells, which can self-renew or differentiate into astrocytes, oligodendrocytes, or neurons that respond to specific stimuli. The regulation of the fate of neural stem cells is a finely controlled process that relies on a complex regulatory network that extends from the epigenetics to the translational level and involves components of the extracellular matrix. Therefore, a better understanding of the mechanisms by which neurogenesis is induced, regulated, and maintained will provide clues for the development of new strategies for neurodegenerative treatment. In this review, we focus on the regulatory mechanisms of transcription factors, microRNAs, and components of the extracellular matrix in neuronal differentiation.

1. Introduction 

Neocortical circuits consist of profoundly interconnected excitatory glutamatergic and inhibitory GABAergic neurons, which are produced from unmistakable pools of RGCs. During embryo development, the excitatory neurons are formed from RGCs confined in the ventricular zone of the dorsal telencephalon and relocate radially toward the pial surface in a back to the front way (spiral movement). Then again, inhibitory neurons fundamentally begin from the ventral telencephalon and relocate digressively into the neocortex (distracting movement). Regardless of such unique formative starting points, both excitatory and inhibitory neurons go through the multipolar stage with a few minor cycles in the neocortex before axon augmentation. Then, at that point, they go through dynamic morphological changes to start axon development, in particular, neuronal polarization. Sakakibara and Hatanaka () assessed the consecutive occasions in polarization cycles of both excitatory and inhibitory neurons, and they talked about the hidden atomic instruments. At the multipolar stage, the excitatory neurons fleetingly utilize a multipolar relocation mode, to be specific movement with no fixed heading, in the subventricular and middle of the road zones. Then, at that point, they receive a bipolar shape during neuronal polarization and relocate rapidly toward the pial surface along with RGC measures, which is called headway mode.

Many types of molecules are involved in these powerful changes in neuron morphology and migration. The small GTP binding protein plays an important role in regulating the development of the cortex and the formation of neurons. The Rnd protein, “abnormal” relatives of Rho, was displayed in neuronal movement, and their ascending and descending pathways were discussed. Many cytoplasmic protein elements, including parts of the cytoskeleton, are managed through phosphorylation and dephosphorylation measures. Ohshima focused on protein kinases, including CDK5 and JNK, and examined their paperwork on cytoskeletal associations during multipolar bipolar progression and extended movement. OhtakaMaruyama and Okado comprehensively summarized the atomic pathways involved in these formation cycles and emphasized the importance of subplate neurons in steering events and the development of the six-layer neocortex design. 

 Pluripotent stem cells are usually derived from embryonic tissue. At least three different types of mammalian pluripotent stem cells have been identified: embryos or cancer cells (CE), embryonic stem cells (ES) derived from the inner cell mass of blastocysts, and embryonic germ cells (EG) derived from post-implantation embryos. In the early 1990s, several groups reported the existence of a subset of stem cells found in the central nervous system (CNS). These cells form the brains of fetal mice or mice that grow in culture and show an almost unlimited lifespan. However, compared to embryonic stem cells, their differentiation potential is more limited and they mainly produce three main cell types of the central nervous system: neurons, astrocytes, and oligodendrocytes, hence the name NSC. These cells have also been isolated from the adult central nervous system, although it is not clear whether these dividing cells are truly pluripotent or whether their fate becomes more restricted during development. For the purposes of this review, NSCs are defined as nerve cells that have the potential to self-renew and generate all the different types of cells in the nervous system after differentiation. 

2. Method

Neuronal differentiation is an early event in mammalian embryogenesis, occurring shortly after germ layer differentiation. The organization of the central nervous system is derived from a well-defined neuroectoderm, the neural plate, which is located in the dorsal midline of the embryo. It appears that neural plaque is produced by signals that locally inhibit or avoid inducing non-neural differentiation. Examples of such signals come from bone morphogenetic protein (BMP) and other molecules of the transforming growth factor-beta (TGF beta) superfamily, which direct epidermal differentiation when gastrulation

Neuronal fate is inhibited by BMP. In the body, several molecules that promote neuronal differentiation, such as noggin, follistatin, and chordates, are antagonists of BMP. Although noggin antagonizes BMP signaling, it is not necessary for the induction of early neurogenesis, because knockout mice are normal at embryonic day 8.5 (although they die at birth). These data indicate that other BMP antagonists can compensate without Noggin expression and illustrate the concept of redundant signaling pathways during embryonic development. The role of BMP is further regulated by the presence of two ubiquitously expressed BMP receptors, BMPR1A and BMPR1B, which do not appear until the 9th day of the embryo. The expression of BMPR1A induces the expression of BMPR1B, and this process is inhibited by the sonic hedgehog. The further development of the neural lamina into mature cells of the central nervous system is clearly and precisely regulated by spatial and temporal differentiation patterns. The growth and proliferation of cells in the early neural plate eventually lead to the closure of the developing nerve sulcus and the formation of a hollow neural tube. The neural tube cavity produces the ventricular system and the epithelial layer contains stem cells that will produce neurons and glial cells of the central nervous system. One of the central problems in developmental neurobiology is the mechanism by which a simple neuroepithelium (only one cell thick) can produce the various cell types that make up the mammalian central nervous system. Currently, there is a large number of studies that have determined the internal factors and external soluble signals that affect this regional pattern and specific neural differentiation. An example of this invertebrate neurogenesis is the transmission of dorsal and ventral patterns of opposing soluble signals: sonic hedgehog (Shh) and BMP antagonists, chordin and noggin, are secreted from the bottom plate, while other signals are emitted from the top plate. Form a gradient. Signal concentration. The precise concentration and ratio of each signal in the neural tube is critical to the development of specific neuronal phenotypes at different points along the gradient. For example, there is a concentration-dependent induction of model genes in progenitor cells encoding homeodomain transcription factors. These differences in expression patterns produce neuronal clusters with different division and differentiation patterns (and ultimately different phenotypes) along the dorsal-ventral axis of the plaque. In humans, the neural tube is formed during the third and fourth weeks of pregnancy. Initially, the neuroepithelial lining consisted of a single layer of neural stem cells with similar morphology. These cells then divide symmetrically to enrich the pool of NSCs or divide asymmetrically to produce a more differentiated progeny from which neurons and mature cells of the glial mass line develop. Although the BMP family of molecules may be involved again, the signals that determine symmetric or asymmetric division are not yet fully understood. 

Retroviral marker studies have been used to identify dividing cells in the ventricular region. Approximately 48% of the labeled cells remained in the colonies in the ventricular zone, indicating self-renewal at this site. In humans and other mammals, the active proliferation of such progenitor cells is likely to be balanced by apoptosis to maintain a stable population, but the exact mechanism has not been determined. As development continues, neurons migrate, partly guided by radially oriented glial processes, and the size of the ventricular area decreases. Neural stem cells are still attached to the basal layer. It has been shown that these cells can divide asymmetrically, and the more differentiated offspring migrate from the ventricular area to the overlying cortex. By obtaining specific phenotypic markers, these cells can divide further and distinguish them from neural stem cells. During CNS development, the temporal pattern causes oligodendrocytes to generate neuronal cell types earlier. In the spinal cord, these two cell populations appear to be produced from a common precursor, and the final decision of fate depends on external signals and specific patterns of transcriptional activation. There are two main types of transcription factors that can determine the fate of neurons or the glia. These are homeodomain factors, an example is NKx2.2, and the basic helix loop helix family of transcription factors, including Olig1 and Olig2. The expression of Olig transcription factors is regulated by external signals (such as Shh), and their expression has been shown to clearly define cells as oligodendrocytes. However, in mice, Olig1 and Olig2 are expressed from E9, long before the presence of oligodendrocyte precursors. At this early stage, Olig2 is known to be the core of neuronal development in specific areas of the ventral spinal cord and is found in cells that can track the fate of motor neurons. The importance of Olig2 in neurodevelopment has been demonstrated in functional gain experiments. As development proceeded, the expression of Olig1 and Olig2 persisted and began to overlap with the homeodomain transcription factor NKx2.2. These doubly positive progenitor cells migrate from the ventral midline and mature into oligodendrocytes. Olig1 and Olig2 have been developed in double-mutant mice. These animals lack oligodendrocytes and also have a considerable loss of motor neurons. In the Olig1 / Olig2 double mutant, the offspring of stem cells in the pMN region of the developing spinal cord generally develop into motor neurons, then oligodendrocytes, but form V2 interneurons and then astrocytes. These results indicate that the expression of the combination of transcription factors determines the fate of the stem cell bank in the developing embryo. However, this does not rule out the existence of more restrictive dividing cell populations. The expression of proglia transcription factors can be regulated by cell surface receptors such as gaps. The jagged1 (notched ligand) signal of neurons has been shown to inhibit the phenotype of oligodendrocytes. Presumably, when the number of neurons is sufficient, jagged1 is down-regulated, and a signal from the original oligodendrocytes (one of which may increase electrical activity) triggers myelination. Once the neural precursor determines the fate of the oligodendrocyte lineage, the last step of honey-forming cell formation needs to exist.

3. Conclusion

All in all, corticogenesis from mouse ESCs shows a setup collection of parent-of-beginning articulation and DNA methylation of engraved loci. This model could be utilized dependably to unwind the atomic components engaged with choosing the communicated parental allele with regard to engraving during the cortical turn of events. Our discoveries likewise give support to utilize ESCs to demonstrate cortical turn of events and for drug screening. The in vitro corticogenesis framework could be an integral asset to pinpoint sedates that de-curb the quieted parental allele in specific mind sicknesses related to irritated IG articulation or to gauge the effect of ecotoxic compounds on the epigenetic marks and the advancement of cortical cells. The cerebral cortex creates through the organized age of many neuronal subtypes, yet the systems included stay hazy. Here we show that mouse undeveloped undifferentiated organisms, refined with no morphogen except for within the sight of a sonic hedgehog inhibitor, summarize in vitro the significant achievements of cortical turn of events, prompting the successive age of a different collection of neurons that show the most notable elements of veritable cortical pyramidal neurons. When joined into the cerebral cortex, these neurons foster examples of axonal projections relating to a wide scope of cortical layers, yet in addition to exceptionally explicit cortical regions, specifically visual and limbic regions, subsequently showing that the character of a cortical region can be determined with no impact from the mind. The disclosure of natural corticogenesis reveals new insight into the instruments of neuronal particular and opens new roads for the demonstrating and treatment of neural disorder.

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About the author

Harsheel Dhruva

Harsheel is currently a Senior at Irvington High School in Fremont, California. Growing up in the Bay Area, he is very interested in the natural sciences and the potential of discovery from advancing technology. He is pursuing studies in Neuroscience and Biotechnology in hope of pioneering his own research in the future and create technology to improve the human condition. Outside of his study, Harsheel loves completing challenging physical activity or listening to music whenever he gets the chance, and is always happy to read something new.

The post Exploring Corticogenesis: Pluripotent Stem Cells into Cerebral Operations appeared first on Exploratio Journal.

Abstract

With about 285 million visually impaired people worldwide, corneal regeneration is becoming a relevant topic of research among the scientific community. In the last decade, scientists have begun to explore the applications of stem cells to treat various corneal diseases, such as burns, limbal stem cell deficiency, aniridia, and many more. This review paper describes various stem cell therapies for corneal regeneration that are currently being used or researched, with a specific focus on limbal, mesenchymal, and induced-pluripotent stem cell therapies,  and provides examples of successful clinical trials supporting the regenerative role of  stem cells for corneal repair.

1.  Introduction

The cornea is a transparent tissue that constitutes the eye’s outermost lens and acts as a mechanical and chemical barrier that protects the inner ocular tissue (Mansoor et al 2019). The cornea also allows light transmission to the retina (Mansoor et al 2019), and it is estimated that 70% of the eye’s refractive power comes from the cornea. The human adult cornea is about 550 μm thick, and is composed of five layers: epithelium, Bowman’s layer, stroma, Descemet membrane, and endothelium (Eghrari et al 2015). The epithelium is the surface layer and serves as the principal barrier for maintaining fluids in the cornea and for preventing pathogens and bacteria from entering in the deeper layers. The Bowman’s layer posteriorly supports the epithelium and assists in the maintenance of stromal hydration and regulates wound healing by thickening around the wound site (Eghrari et al 2015). The stroma makes up the majority of the cornea’s volume, contributes to clarity, and assists in ocular immunity (Alio Del Barrio et al, 2021). The posterior part of the cornea is composed of the Descemet membrane and the endothelium. Both of these layers are vital for stromal hydration. During embryo development, the cornea first develops with the formation of the epithelium, followed by the production of the stroma and endothelium. Lastly, the Descemet membrane is secreted by the endothelium and the layer thickens (de Oliveria et al, 2020). Currently, there are about 285 million visually impaired people worldwide, with 39 million suffering from blindness. Over 10 million of these cases are caused by corneal diseases that can be caused by traumatic injury, chemical burns, infections, iatrogenesis, age-related degeneration, and corneal dystrophy (Masoor et al 2019). These diseases can cause defects to the cells and the extracellular matrix of the cornea and can cause visual impairment through the formation of corneal scars, haze, and opacities (Mansoor et al 2019), which often lead to blindness if not treated. 

The most frequently performed procedure to treat corneal defects is allograft corneal transplantation, which consists in replacing the patient’s damaged cornea with a healthy cornea from a donor. However, this treatment is not ideal as there is limited donor tissue and allograft survival, as well as the need for long-term use of immunosuppressants for patients. Furthermore, many patients cannot get transplants due to the high surgical and rehabilitation costs. Costs of transplantation can cost over $11,000 per year for one person in developed countries. In developing countries, the cost of transplantation can be expected to be much more significant, over double the costs of developed countries (Mansoor et al 2019). Thus, researchers have been looking into corneal treatments based on stem cell technology, as they provide an alternative method to corneal treatment that is not as costly or limited by tissue availability.

2.  Stem cell therapies for corneal regeneration

Stem cells are undifferentiated cells that can extensively proliferate and differentiate into different types of cells and tissue (Kolios et al 2013). Advantages of using stem cells therapy for corneal regeneration include the ability to treat a wide spectrum of corneal pathologies, such as blindness and visual impairments (Shukla et al 2019), classical and rare ocular diseases, chemical burns, and limbal stem cell deficiency (Shukla et al 2019). This review paper will cover the most effective stem cell-based treatments developed for cornea regeneration, which exploit the use of limbal, mesenchymal, and adipose-derived stem cells for regenerating damaged or diseased cornea tissues.

2.1. Limbal stem cells

Limbal cells can be found in a narrow zone between the cornea and the bulbar conjunctiva (Rama et al 2010). They maintain homeostasis in the cornea and can cause decreased vision and recurrent epithelial erosions if deficient (Shanbhag et al 2020). Limbal stem cells have the capacity for self-renewal, proliferation, and migration, which make them indispensable for corneal regeneration. Limbal stem cells can be isolated and cultivated in vitro by taking small biopsies of primary cells from human eyes with a minimally invasive procedure (Bremond-Gignac et al, 2018). Researchers have used both autologous cells, i.e. cells isolated from the patient’s healthy eye, and allogeneic cells, that can be isolated from another individual or from a cadaver, for corneal regeneration therapy. Autologous cells are used in cases where only one eye is diseased, and these cells ensure compatibility with the diseased cornea. Allogenic cells are used if both eyes are diseased, but this treatment may require long-term topical or systemic immunosuppressive medication (Bremond-gignac et al, 2018). Limbal stem cells are used mainly for limbal stem cell deficiency (LCSD) and ocular burns (Shanbhag et al 2020). Various techniques are currently investigated to deliver limbal stem-cells to the cornea, which include CLAu (conjunctival-limbal autografting), CLET (cultivated limbal epithelial transplantation), and SLET (simple limbal epithelial transplantation) (Shanbhag et al 2020). CLAu is the traditional method of limbal stem-cell therapy and involves direct transplantation of two conjunctival-limbal lenticules from a healthy eye onto a diseased limbal bed. Autologous CLAu is advantageous as it boasts high efficacy and patients do not need immunosuppressants. CLET is a procedure that consists in taking a 2mm-by-2mm limbal biopsy from a donor eye, isolating and expanding the cells ex-vivo in a clean room for 10-14 days, and then transplanting the grown cells onto the surface of a diseased eye (Bakhtiari et al, 2010). The main advantage of this technique includes the possibility of harvesting a smaller biopsy compared to CLAu, however there are large costs for this procedure and the efficacy is lower than that of CLAu. The SLET method instead is performed by harvesting a strip of donor limbal tissue from a healthy eye, but instead of expanding the cells ex-vivo, the tissue is divided into small pieces and transplanted directly onto a diseased eye for in-vivo expansion. The efficacy of this treatment is similar to that of CLAu and requires a smaller tissue from the donor eye than CLAu. Several clinical studies have shown that limbal stem cell therapy has been proven effective in the treatment of burn-related corneal destruction. In a study from (Rama et al, 2010), renewal of the corneal epithelium was demonstrated in 76% of transplanted limbal stem cells (n=113) delivered on a fibrin substrate with the CLET method. In a study from (Gupta et al 2018), researchers adopted the autologous SLET approach and found that 70% of the treated eyes maintained a successful outcome (n=30). Some disadvantages of LSCT include the dangers of the cultivation process, as allogenic cells can be immunogenic. Furthermore, there is still a lack of a universal and established protocol for limbal stem cell culture in vitro, and the variability of the cell culture conditions among different research groups may influence the outcomes of the clinical trials. 

Overall, the studies, Rama et al 2010 and Gupta et al 2018, along with other recent advances in the field demonstrate that limbal stem cells show great potential for corneal regeneration therapies for ocular diseases.

3.  Mesenchymal stem cells

Mesenchymal stem cells (MSCs) have been researched as a potential treatment of corneal diseases due to their regeneration and differentiation capabilities. MSCs can be isolated from fetal tissues such as first-trimester blood, bone marrow, placenta, umbilical cord, and amniotic fluid (Mansoor et al 2019). In adults, they can be isolated from bone marrow, peripheral blood, adipose tissue, dermis, synovium, periosteum, cartilage, skeletal muscle, fallopian tubes, menstrual blood, gingiva, and dental tissue (Mansoor et al 2019). MSCs can also be found in the eye, in the corneal stroma and trabecular meshwork (Mansoor et al 2019). Though MSCs can be isolated from a variety of fetal and human tissues, the most typical sources of isolation of MSCs are the bone marrow and the adipose tissue. One way bone marrow MSCs are isolated is through plastic-adhesion. This technique consists of collecting MSCs by specific bone marrow aspiration and selected by their different kinetics of adhesion to the tissue culture vessels (Chu et al 2020). This method is simple and convenient for most researchers, Though effective, extracting the bone marrow from the iliac crest of patients can result in pain, bleeding, or infection, which can make it problematic (Fridman et al 2018). Recently, researchers have been looking for alternatives to bone marrow extraction, which has resulted in MSCs being derived from adipose tissue. These can be more safely and easily isolated, usually resulting in higher yields of isolation (Strioga et al 2012). To isolate adipose tissue MSCs, subcutaneous adipose tissue is used in the form of lipo-aspirates or larger tissue pieces harvested during orthopedic surgery. The mesenchymal stem cells are extracted by finely chopping the tissue and putting it in an enzymatic solution to digest the extracellular matrix, followed by culturing the cells. on culture dishes. (Mushahary et al 2018). MSCs can be isolated also from the cord lining of the human umbilical cord, by dissecting Wharton’s jelly (Mushahary et al 2018). These cells can be used to promote tissue repair and modulate immune responses and anticancer properties (Ding et al 2015). Advantages of fetal-derived MSCs include their longer, more active telomeres and greater proliferation capacity. However, these cells require rigorous ex vivo expansion in order to be used (Mansoor et al 2019). Most studies using MSCs for corneal regeneration have used allogeneic cells. So far, only bone-marrow derived MSCs have been utilized for corneal regeneration purposes, and they have shown to improve corneal re-epithelization. Allogenic bone-marrow derived MSCs have been used to treat limbal stem cell deficiency, in a clinical study performed by Calonge et al (2019). These cells were transplanted through surgery in the cornea. Out of 17 cases given MSC treatment, 85.7% were successful 12 months after surgery (Calonge et al 2019). 

MSC treatment can be also administered systemically, using intravenous or intraperitoneal injections, to improve clinical signs in eyes (Galindo et al 2021). A key aspect of fMSCs use for corneal treatments is related to their anti-inflammatory properties, as it has been demonstrated that these cells produce minimal inflammatory response in corneal mechanical damage models (Galindo et al 2021).

Besides being used for transplantation in diseased eyes or for systemic infusion, MSCs can be also cultured in vitro for producing exosomes, unique vesicles containing proteins and genetic information that can be used for regenerative medicine. MSC-derived exosomes can repair tissue damage, suppress inflammatory responses, and modulate the immune system. In addition, exosomes are more stable and reliable, present no risk of aneuploidy (presence of an abnormal number of chromosomes in a cell), and lower chances of immune rejection compared to MSCs. While the mechanisms of exosomes regenerative function are still controversial and not well-understood (Yu et al 2014), they are widely studied for corneal regeneration, as they can be involved in regulating tissue wound repair, inflammation, angiogenesis, and immune response.

4.  Induced pluripotent stem cells

Through future research, corneal regeneration may be possible using induced pluripotent stem cells (iPSC). The ability to reprogram somatic cells into iPSCs offers a chance to generate pluripotent patient-specific cell lines that can be used for a variety of diseases (Malik et al 2013). The original way of generating iPSCs was through reprogramming adult human dermal fibroblasts. Through modifying the reprogramming factor expression vectors and experimenting with new modes of delivery, researchers are finding ways to increase efficiency and efficacy of this treatment method. Since iPSCs are easily expandable, they are considered as an unlimited and renewable cell source (Ljubimov et al 2015). However, the current hurdle for corneal regeneration using these cells relates to the optimization of the differentiation of these cells (Ljubimov et al 2015). Currently, iPSCs have been differentiated into limbal epithelial cells using feeder cells, embryoid bodies, and the stromal cell-derived inducing activity method (Zhu et al 2010). But these methods are not yet optimized, which means iPSCs must be further tested and refined for cornea treatments. To the best of our knowledge, there is still no clinical trial using iPSCs for the regeneration and repair of the cornea. However, on the overall, these stem cells can constitute a robust and promising resource for cornea treatments.

5.  Conclusion

Currently, there are about 285 million visually impaired people worldwide, with 39 million suffering from blindness. Over 10 million of these cases are caused by corneal diseases (Mansoor et al). To combat this, scientists have been researching ways for corneal regeneration. An innovative and interesting way for corneal regeneration is being researched in the use of stem cells to treat various corneal problems. The use of stem cells like limbal and mesenchymal stem cells have shown great promise in clinical studies. In addition to these, induced pluripotent stem cells are potential candidates for further advancing the field of cornea regeneration as it is a unique and innovative treatment. Therefore, there is no doubt in the recent progress in stem cell treatment for the cornea and the viability of stem cell treatments for corneal diseases in the near future. 

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About the author

Akshay Gupta

Akshay is a junior at the Chattahoochee high school in Johns Creek, Georgia. He has a strong passion for biology and life sciences. Besides his academic interest in biology, he plays competitive tennis and enjoys working with computers, whether it is building a PC or playing video games.

The post Stem Cell Therapies for Corneal Regeneration appeared first on Exploratio Journal.

Abstract

 Stem cells have been a prevalent research field for their versatile use as a potential treatment of several different diseases that have remained untreatable, such as Alzheimer’s disease. These cells are unspecialized cells that can replicate themselves indefinitely (self-renewal) and give rise to more specialized cells (differentiation). Due to these unique properties, stem cells can be described as the foundation for all tissues and organs in the human body. Stem cells can be mainly classified into 3 categories: embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and adult stem cells. The different distinctive characteristics of each category of stem cell as well as their applications in the potential treatment development of Alzheimer’s Disease are discussed in this manuscript.

1. Introduction

In the last decade, stem cells have raised great interest in the scientific community due to their promising use in the fields of regenerative medicine, drug testing and discovery and modeling of healthy and diseased tissues. Stem cells are undifferentiated cells that can be isolated from embryos (embryonic stem cells, ESCs), from adult tissues (adult stem cells) or can be generated by reprogramming somatic cells, such as dermal fibroblasts (induced pluripotent stem cells, iPSCs) (Zakrzewski et al, 2019, Shi et al, 2017).  The three different types of stem cells each have potential advantages and disadvantages that may encourage or limit their use for medical applications. Embryonic stem cells are pluripotent, meaning that they can differentiate or specialize in any cells of the body, with the exception of the extraembryonic cells, which constitutes the placenta and the umbilical cord (Zakrzewski et al, 2019).  While pluripotency and plasticity makes ESCs the most desirable cell type for regenerating diseased tissues, ESCs raise the ethical issue of using them since their isolation from the inner cell mass destroys the embryo (Abdulrazzak et al, 2010). Additional to their ethical concerns, because of their pluripotency and proliferative ability, they can form tumors after transplantation (Hess et al, 2019). Because of their limited proliferative capacity, adult stem cells do not raise this issue, however they are much harder to culture in vitro and are considered multipotent or unipotent, in that they can only differentiate into fewer or just one specific cell type. Induced pluripotent stem cells are a rather new discovery so not much is known about them on their use for potential treatments, however they are the most promising because of their versatility and easy access (Shi et al, 2017). Similar to ESCs, iPSCs have the potential issue of tumor formation due to their proliferative ability. 

2.1. Embryonic stem cells (ESCs) 

Embryonic stem cells are stem cells that are found in the inner cell mass of a blastocyst. A blastocyst is a bundle of cells formed 5-6 days after fertilization of the oocyte by the sperm cell that undergoes cell division by meiosis (Yu and Thompson, 2006). ESCs have been differentiated in multiple  cells types such as cardiac cells (Liu et al, 2018) , vascular smooth muscle cells (Cheung et al, 2011) , nerve cells (Magown et al, 2017, Jones et al, 2018) and retina cells (Lakowski J, 2015,Mehat et al, 2018) to form healthy tissues that can be transplanted in injured or diseased areas of the body. ESCs can be easily identified and isolated from the inner cells of the blastocyst (Sills et al, 2005) and can be cultured and grown indefinitely in a lab setting to be used for research in medicine and science. These extracted stem cells are extremely valuable and have shown great potential for regenerative treatments as well as for drug development and testing (Yu and Thompson, 2006).

2.2. Induced pluripotent stem cells (iPSCs)

Induced pluripotent stem cells are derived from somatic cells such as skin or blood cells and are reprogrammed into an embryonic-like state (Shi et al, 2016). Researchers associated pluripotency, unique to ESCs, with genes or factors that are only expressed by ESCs. In 2006, Shinya Yamanaka, identified four genes (Myc, Oct3/4, Sox2 and Klf4) with encoded transcription factors that could convert somatic cells into pluripotent cells (Zhao et al., 2013). The reprogramming of somatic cells with the introduction of these four genes led to the discovery and use of iPSCs which have paved a way to more efficiently identify and model disease cells that were not very successful in animal models. After their discovery, iPSCs have provided a strong headway into regenerative medicine, to repair damaged cells, tissues or organs. When conducting a normal tissue or organ transplant, it is imperative that the cell, tissue or organs donor’s physiological profile matches that of the patient. Not being able to meet these specific conditions is one of the common reasons patients die in urgent situations of accidents or patients who have been suffering degenerative diseases. The use of iPSCs, that can be reprogrammed from the healthy cells of the same patient, can greatly reduce the risks that come with transplants. Since iPSCs can be directly generated from skin and blood cells of patients, the cells which will be transplanted are from the patient’s own body. In addition, patient-specific iPSCs allow researchers to look more closely at the disease relevant cells in the patient’s body.

2.3. Adult stem cells 

In contrast to embryonic stem cells, adult stem cells or somatic stem cells are stem cells found in the adult body, especially in the bone marrow, blood vessels and in the adipose tissue (Stem cells, 2001). They are found in the adult tissues and are more difficult to expand in a lab setting since they do not duplicate as easily as ESCs and iPSCs (Stem cells, 2001), therefore they can be cultured for a lower number of passages in vitro, yielding smaller numbers of cells. These cells are more specialized compared to ESCs and iSCs and usually only give rise to limited types of cells, dependent upon the tissue type they have been isolated from (Stem cells, 2001). For example, stem cells found in the bone marrow differentiate into red blood cells, white blood cells, and platelets, however, they will not differentiate into cells of other tissues, such as liver, or brain cells. In a few cases, it has been demonstrated that adult stem cells of various tissues could be reprogrammed into IPSCs (Labusca et al, 2019) 

3. Use of stem cells for treating Alzheimer’s disease (AD)

Alzheimer’s, a disease characterized by memory loss and cognitive impairment has troubled society due to its unknown causes as well as lack of treatment for the disease. With the transplantation of stem cells, researchers can investigate how these regenerative cells could potentially slow down the development of AD in the brain as well as using them as new drug screening platforms by differentiating them into multiple brain cell subtypes.

3.1 In vitro models of AD 

The use of stem cells for the development of in vitro platforms for drug screening and discovery allow to create patient-specific models of diseases, including AD. With these models, it is possible to examine the effects of promising drugs on the cell types most relevant to AD and to screen through a variety of compounds that directly target parts of the brain in relation to the disease itself.

In this context, stem cells are used as a source to differentiate healthy cells of the brain for studying molecular pathways and physiologic/pathologic cell phenotypes in vitro. In particular, ESCs and iPSCs have been differentiated into different cells of the brain, including distinct neuronal and glial cell subtypes, as well as astrocytes (Little et al, 2019).

Furthermore, cells from patients carrying specific mutations associated to AD have been isolated and reprogrammed to iPSCs and further differentiated into neurons, to determine the optimal, patient-specific treatment to attenuate the effects of the pathology (Yagi et al, 2011, Israel et al, 2012, Muratore et al, 2014).

3.2 Stem cell therapy for AD

In addition to drug screening applications, stem cells can be directly used as therapeutic agents to slow down the progression of the disease. 

Arnhold et al. demonstrated for the first time the possibility of differentiating ESC-derived neural precursor cells into neurons and astrocytes directly after transplantation in adult rat brain (Arnhold et al., 2000). The authors also demonstrated that the precursor cells were mature and fully functional after transplantation. Several studies showed that after transplantation, ESCs are able to integrate with other cell types in the brain (Nasonkin et al., 2009) and secrete reparative molecules to regenerate injured regions (Zhang et al., 2006). Furthermore, it has been demonstrated that the ESC-derived neuron precursors are able to integrate with the host brain tissue. Aubry et al (year) suggested that the optimal number of cells to be implanted has been found to be 15×103 cells per animal.

iPSCs therapy is relatively new for Alzheimer’s disease. There are several studies in literature focused on the use of iPSCs for developing 2D and 3D models of brain diseases, including Alzheimer’s disease. Since iPSCs can be derived from AD patients, researchers have the ability to look at the specific genes and molecular pathways  associated with the disease in the neural cells (Shi et al., 2017). Furthermore, since these cells self-renew themselves, researchers can recapitulate how the disease grows and progresses and behaves in simple in vitro disease models (Shi et al., 2017).

Furthermore, it has been recently demonstrated that neurons can be successfully differentiated from fibroblasts (skin cells) reprogrammed into iPSCs (Liu et al, 2012). These cells have demonstrated similar morphology and function as these of the neural cells in the brain. Transplanted iPSCs-derived neurons are able to survive, maintain their function and even mature into the brain of mice models (Eckert et al 2015, Fujiwara et al, 2013). Promising therapeutic effects have been shown by Eckert et al, that demonstrated attenuated post-stroke effects and augmented neurological function in a mice model of stroke starting only 24 hours after the injection of iPSC-derived neurons (Eckert et al, 2015).

Fewer research studies are available that use adult stem cells for brain regeneration and AD. Stem cell therapy with adult stem cells often involves the use of mesenchymal stem cells (MSCs) and their expansion and  differentiation into neural cells (Liu et al., 2020) however these cells exhibited a low yield of differentiation and decreased stability compared to ESCs- and iPSCs-derived neurons when transplanted in vivo.

4. Conclusion

This paper describes just a few out of many examples of how stem cells can be used for the cure and research of AD. There are countless diseases in the world today with no known cure, but extensive research of stem cells could bring about countless possibilities and opportunities in which they can be used to cure untreatable diseases through applications in regenerative disease as well as disease modeling. Stem cell ability to differentiate into any cell type  and to recapitulate patient-specific diseases will allow for more ground-breaking methods and treatments to be discovered by studying more thoroughly at how the disease behaves. With more research on the use of stem cells for Alzheimer’s Disease, researchers will be able to look at the development of AD in neural cells and hopefully show promising results for a treatment that no one will fail to remember.

Stem cells which could be described as the most basic form of life were discovered about 30 years ago. These small cells which are in their simplest forms not only give rise to the most complex structures in the body but also show a hopeful future and solution for devastating diseases in the world today. It’s a gift in the simplest of essences yet in the most intricate of ways.

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About the author

Dana Chung

Dana is a student at the Coventry Christian School in Pennsylvania.

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