Although scientists use the term stem cell quite broadly, there are numerous stem cell types with many different therapeutic purposes.
Download this infographic from Drug Discovery News for a quick guide to induced pluripotent, cord blood, mesenchymal, and various adult stem cells.
The Hitchhiker’s Guide to Stem Cells
How do scientists choose between an ever-growing number of stem cells?
BY TIFFANY GARBUTT, PHD
DESIGNED BY SHANNON HERRING
UNLOCKING POTENTIAL
Since their discovery in the early 1960s, scientists hoped that stem cells would unlock a new era of therapeutics. The ability of stem cells to differentiate into various cell types and proliferate indefinitely offers treatment possibilities for a plenitude of ailments. Today, there are more than 9,000 stem cell clinical trials (1). There are many different types of stem cells, each with its own properties that may be best suited for different kinds of treatments and research.
HEMATOPOIETIC STEM CELLS
The only stem cell therapies approved by the United States Food and Drug Administration (FDA) use hematopoietic stem cells (HSCs). First discovered in 1961 by Ernest McCulloch and James Till, HSCs were the first known stem cells (2). HSCs differentiate into all blood lineage cells and are used in bone marrow transplantation to treat blood and immune system disorders or to replenish HSC levels after some types of cancer treatments.
CORD BLOOD STEM CELLS
HSCs in infant umbilical cord blood are more primitive than HSCs in adult bone marrow. They are more abundant and proliferative, produce more growth factors and immune-modulators, and have lower immunogenicity than their adult counterparts. The FDA has approved HSCs from cord blood for treating nearly 80 diseases. Almost 350 clinical trials are underway using cord blood to treat various conditions including anemias, inherited metabolic disorders, and immune system deficiencies (3).
MESENCHYMAL STEM CELLS
First characterized in the 1970s by Alexander Friedenstein, mesenchymal stem cells (MSCs) are a type of multipotent adult stem cell derived from the bone marrow (4). MSCs differentiate into bone, fat, cartilage, muscle, and connective tissue. Unlike other stem cells, MSCs navigate to injury sites, suppress immune responses, and secrete growth factors that activate other resident stem cells (5). These additional properties make MSCs the most widely explored stem cells. More than 1,000 ongoing clinical trials use MSCs for autoimmune, cardiovascular, neurodegeneration, and tissue regeneration studies (1).
EMBRYONIC STEM CELLS
Discovered in the 1980s in mouse embryos, embryonic stem cells (ESCs) derive from the inner cell mass of the developing blastocyst. During development, these cells differentiate into all cell types of the body, making them ideal for tissue regeneration and organoid studies. Scientists first isolated ESCs from human embryos in 1998 (6). Today, 39 ongoing clinical trials use historically derived ESCs (1).
INDUCED PLURIPOTENT STEM CELLS
Generated by Kazutoshi Takahashi and Shinya Yamanaka in 2006, induced pluripotent stem cells (iPSCs) are the youngest discovered stem cell (7). iPSCs are differentiated cells that have been reprogrammed into an embryonic stem cell-like state and offer the hope of producing patient-derived stem cells. In 2014, Masayo Takahashi implanted iPSC-derived retinal epithelial cells into the eyes of a patient with age-related macular degeneration (8). Today, iPSCs account for 60 ongoing clinical trials (1). iPSCs may also have utility as renewable sources for allogeneic CAR T cells (9).
ADULT STEM CELLS
Specialized stem cells exist in almost every tissue in the adult body where they play critical roles in tissue maintenance and repair. HSCs and MSCs represent two types of adult stem cells. Other adult stem cells include neural stem cells, epithelial stem cells, and skin stem cells. Harnessing the multipotent activity of resident tissue cells presents the possibility of endogenous tissue regeneration (10).
REFERENCES
1. Clinical Trials. National Institute of Health, United States National Library of Medicine. www.clinicaltrials.gov/ct2/home
2. Becker, A. J., McCulloch, E. A., & Till, J. E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197, 452-454 (1963).
3. Treating Diseases. CryoCell International. www.cryo-cell.com/treatments-and-research
4. Friedenstein,A. J., Chailakhjan, R. K., & Lalykina, K. S. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3(4), 393–403 (1970).
5. Saeedi, P., Halabian, R., & Imani Fooladi, A. A revealing review of mesenchymal stem cells therapy, clinical perspectives and Modification strategies. Stem Cell Investigation 6, 34 (2019).
6. Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 6(282), 1145 – 1147 (1998).
7. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4), 663-676 (2006).
8. Cyranoski, D. Japanese women is first recipient of next-generation stem cells. Nature. (2014).
9. Fate therapeutics announces treatment of first patient in landmark phase 1 clinical trial of FT819, the first-ever iPSC-derived CAR T-cell therapy. Fate Therapeutics. ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-announces treatment-first-patient landmark#:~:text=FT819%20is%20the%20first%2Dever,availability%2C%20and%20broader%20patient%20accessibility (2021).
10. Watt, F. M. and Driskell, R. R. The therapeutic potential of stem cells. Philosophical Transactions of the Royal Society B: Biological Sciences UNLOCKING POTENTIAL 365, 155-163 (2010).