Stem Cell Research

By definition, stem cells have two distinct attributes. They can simultaneously divide and create identical copies of themselves while simultaneously holding the ability to divide and create cells that can differentiate into any cell in an organism.

To understand stem cells, it is important to look at their origin. A blastocyst, formed from the fusion of sperm and ovum, is composed of two distinct cell types, the inner cell mass and the trophectoderm. The trophectoderm functions to form a specialized structure for extraembryonic support, and as this happens, inner cell mass cells remain pluripotent and proliferative to form embryonic stem cells (ESCs). After ESCs differentiate into one of the germ layers they become multipotent and specialize into specific tissues in the fetus, and later on, in adult organisms. These signals that influence stem cell differentiation can be external, for example through physical contact between cells or surrounding tissues, as well as internal, as in signals controlled by genes in DNA.

Stem cell replenishment and formation by the body can be unlimited, though their unique activity depends on the organ in which they reside. For instance, in bone marrow stem cell division is continuous, though in the pancreas, stem cell division only occurs under unique physiological conditions. This constant division and differentiation potential allow stem cells to act as an innate repair system within the body.

Stem Cell Subtypes

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Stem cells can also be categorized into subtypes. Pluripotent stem cells (PSCs) occur ubiquitously as undifferentiated cells and are those that can proliferate by the formation of new stem cells and differentiate under unique physiological conditions. When isolated and grown in a laboratory, PSCs can continue dividing indefinitely. ESCs are derived from PSCs, though they exist only at the earliest stages of embryonic development.

Adult stem cells are found in various tissues and organs, and exist to replace cells lost to natural turnover, damage, or disease. Adult stem cells, also known as tissue-specific stem cells, are committed to becoming a cell from their tissue of origin. Like PSCs, in laboratory setting once an adult stem cell line is established it can be grown indefinitely.

Another subcategory of stem cells includes induced pluripotent stem cells (iPSCs). Before iPSCs, starting cells must be taken from tissues, normally skin or blood, which are then genetically modified to behave like ESCs. Lastly, cancer stem cells are those that function to spread cancer and maintain the ability to mature into various tumorigenic cells. Cancer stem cells are less understood, though they have generated much interest in research for their potential for use in cancer therapies.

Pluripotent Stem Cells in Research

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The self-renewal and potency capabilities of PSCs make them, understandably, attractive sources for cell therapies and within the last two decades both ESCs and iPSCs have become ideal candidates in the clinical setting. There exist two main concerns, however, involving the use of ESCs: ethical issues regarding the use of human embryos and the possibility for a negative immunologic response after transplantation. To overcome these issues, some research has involved generating ESCs from a patient's own somatic cells by nuclear transfer, though this is often technically challenging. iPSCs are instead obtained by inducing the dedifferentiation of adult somatic cells through a recently developed in vitro technology, known as cell reprogramming.

Similar to ESCs, iPSC can be expanded indefinitely and are capable of differentiating in all the derivatives of the three germ layers. Though PSCs hold a huge potential for use in transplant therapies, if these cells continue to proliferate after transplantation or if genetic mutations occur during the in vitro culturing process, PSCs may result in tumors and teratomas or induce tumorigenesis.

Though human PSCs have the potential to transform current understanding of cellular and molecular biology, as with most novel biologics, therapeutic use comes with challenges. Successful PSC-based therapies must continue to address issues related to tumorigenicity, immunogenicity, and biodistribution. This, however, should not understate the potential benefits of PSCs. In studying biology, PSCs can be used as a powerful system to study gene function and the physiology of development. In biomedical fields, PSCs can be utilized to study genetic diseases, to identify new biomarkers, or even to test and improve medicine.

In the clinic, PSCs hold great potential in regenerative medicine to treat damaged or diseased tissues. Amongst other things, applications of PSCs have also been researched to combat neurodegenerative disorders, to research fertility diseases, for regenerative dentistry, in high-throughput drug screening, as an alternative to arthroplasty, to investigate embryotoxicity, and to study pharmaceutical-associated morbidity and mortality.

Application Notes:
Matrix Remodeling Maintains Embryonic Stem Cell Self-Renewal by Activating Stat3 GAPDH is critical for superior efficacy of female bone marrow-derived mesenchymal stem cells on pulmonary hypertension	Use of human iPSC-derived cardiomyocytes to monitor compound effects on pathways High-Content High-Throughput Assays and iPSC Neuronal Cultures

Regenerative Medicine

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Regenerative medicine is a field of research with the ambitious aim of using stem cells to replace damaged tissues and organs. Scientists Shinya Yamanaka and Kazutoshi Takahashi have been praised as pioneers in regenerative medicine as their work effectively reprogrammed multipotent adult stem cells into the pluripotent state, creating the first studied iPSCs. This success opened a new field in stem cell research through the generation of highly customizable and biocompatible cell lines.

Recently studies have expanded upon this work and focus on reducing carcinogenesis and improving the distribution of these cells correctly throughout the intended tissues. As the current need for transplantable tissues and organs outweighs the possible supply, stem cells appear to be a perfect solution. Noteworthy research performed in animal models has shown incredible potential for PSCs in the field of regenerative medicine; this work has paved the way for PSC use in clinical trials. A current research database has identified over 100 clinical studies using human PSC lines that generally circulate around four different areas of medicine; degenerative eye diseases, neurodegenerative disorders, type 1 diabetes, and cardiovascular disease.

Other novel clinical trials involving PSC are aimed at investigating the differentiation of hematopoietic stem cells for leukemia and blood disorders, the creation of liver organoids for treating liver failure, and the creation of kidney organoids for kidney failure. PSCs could provide powerful use in future healthcare, and ongoing research could ultimately bring the promise of regenerative medicine into a clinical reality.

Application Notes:
Early pathogenesis of Duchenne muscular dystrophy replicated using stem cells Restriction of Advanced Glycation End Products Improves Insulin Resistance in Human Type 2 Diabetes	Attenuation of lysyl oxidase and collagen gene expression in keratoconus patient corneal epithelium corresponds to disease severity Developing high-content assays for hepatoxicity with iPSC-derived cells

Product Ordering Information

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References

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Pluripotent Stem Cells: Current Understanding and Future Directions
Stem Cell Key Terms
Chapter 15 - Considerations in the Development of Pluripotent Stem Cell-based Therapies
Pluripotent Stem Cell-Based Cell Therapy—Promise and Challenges
Stem cells: past, present, and future
Induced Pluripotent Stem Cells for Regenerative Medicine
History and current status of clinical studies using human pluripotent stem cells
Pluripotent Stem Cells in Clinical Setting—New Developments and Overview of Current Status