By Manil Chhin
Since the mid-20th century, stem cell research has sparked a lot of intrigue among medical doctors, researchers, and the general public. However, this also raises some ethical and safety concerns with the clinical applications of stem cells. This essay aims to discuss the controversies surrounding the use of stem cells in clinical medicine, and to inform the general public about the ongoing debate over the appropriate applications of stem cell research and therapy.
Stem cells are undifferentiated cells that have two properties: self-renewal and potency (Bioninja). Self-renewal refers to the ability of stem cells to ‘differentiate’ into specific cells that have a specific structure to perform a function in the body. Differentiation is the process by which a less specialized cell becomes a more specialized cell type (Ruth). Potency describes the ability of stem cells to indefinitely divide and replicate to differentiate into specialized cells. Examples of specialized cells include neurons specialized for electrical signal transmission and cardiac muscle cells specialized for rhythmic contractions that pump blood around the body. Stem cells make more than 200 specialized cells among the trillions of cells in your body (Cona).
There are four main types of stem cells’ potency at various stages of human development (Ruth). Totipotent cells can form any cell type and develop into entirely new organisms and pluripotent cells can form all cell types from any of the three germ layers (ectoderm, endoderm, mesoderm). A germ layer is defined as “a group of cells in an embryo that interact with each other as the embryo develops and contribute to the formation of all organs and tissues” (MacCord). Multipotent cells can only form a multiple of closely related cell types, and unipotent cells can only differentiate into one type of cell. Totipotent stem cells (e.g. zygotes) and pluripotent stem cells are considered to be embryonic stem cells, while multipotent stem cells (e.g. bone marrow) are considered to be adult stem cells (Bioninja). Embryonic and adult stem cells can be used therapeutically to treat diseases by repairing tissue and replacing damaged cells with healthy ones (Ruth).
While embryonic stem cells have a greater potency (they can treat more conditions), there are ethical issues associated with their use in human embryonic stem cell (hESC) research (Cona). hESCs are pluripotent stem cells derived during early embryonic development (Vladislav Volarevic et al.). This means they can differentiate into cells from all three germ layers. Thus, hESCs have been widely used in research for understanding human development and disease mechanisms. However, isolation of ESCs involves the destruction of a human embryo, which remains a major factor that has slowed down the development of hESC-based clinical therapies (Cona). Therefore, the main question arises: Is it ethical to pursue therapies for curing illnesses at the expense of destroying an early human embryo? Legislations have been made in countries regulating hESC research. For instance, since 2001, many countries, like the United Kingdom, allow the use of hESCs for research (Vladislav Volarevic et al.). However, countries like Italy prohibit all hESC-based research. That being said, it is legal to use in-vitro fertilization (IVF) derived embryos for derivation of new hESCs lines instead of destroying human embryos (Vladislav Volarevic et al.). In addition, the transplantation of undifferentiated ESCs can lead to the uncontrolled growth of these pluripotent cells, resulting in the formation of teratomas and tumors (Vladislav Volarevic, et al.). Currently, the only way to ensure that teratomas will not develop is to use a combination of growth factors and signaling molecules to guide the differentiation of ESCs into the desired cell types before injection. After following this procedure, while there are less teratomas developed in over 200 animal models, unwanted and uncontrolled differentiation of hESCs was still noticed (Vladislav Volarevic et al.). Despite this result, further research suggests that under controlled conditions, hESC-derived cells could serve as a potentially safe new source in regenerative medicine (Song et al.).
Another clinical application of embryonic stem cells is Induced Pluripotent Stem Cells (iPSC) technology. iPSC are very similar to hESCs, but unlike hESCs, they do not require the destruction of embryos (Vladislav Volarevic et al.). Instead, iPSCs are generated by reprogramming adult somatic cells of the patient, such as skin or blood cells, into a pluripotent state (Cona). While iPSCs can be used as a reproductive technique that can correct genetic mutations of the gamete before transplantation and has no risk of graft rejection, there exists the safety risk of teratoma formation when patients receive iPSC-derived cells that contain undifferentiated iPSCs (Vladislav Volarevic et al.).
In contrast, the use of adult stem cells has less ethical issues (no destruction of embryos) and a lower chance of graft rejection. However, adult stems stells have lower potency and are, therefore, limited in their potential use. An example is Mesenchymal Stem Cells (MSCs), which are multipotent cells isolated from the bone marrow, adipose tissue, and umbilical cord blood (Cona). MSCs have been applied clinically in patients with inflammatory bowel diseases (IBD), liver disorders and cardiac diseases with very encouraging results (Vladislav Volarevic et al.). However, a safety issue is the potential for MSCs to differentiate into undesired tissues, like bone and cartilage, in unwanted structures like the heart. Also, MSCs can generate new blood vessels, which can potentially lead to tumor growths and cancers in patients (Vladislav Volarevic et al.).
Overall, the current ethical and safety controversy seen across the three stem cell therapies is the unwanted differentiation of cells and the potential malignant transformations from it. More protocols should be optimized in order to ensure the purity of the populations of differentiated cells before their clinical use. More research on long-term follow-ups is needed to fully determine other possible effects of these treatments.
Works Cited
Cona, Louis A. “Stem Cell Research Controversy: A Deep Dive (2024).” Dvcstem.com, 5 June 2024, www.dvcstem.com/post/stem-cell-research-controversy. Accessed 9 June 2024.
Illustration of stem cells. Cell Genesis, cellgenesis.com.my/.
MacCord, Kate. “Germ Layers | Embryo Project Encyclopedia.” Asu.edu, 17 Sept. 2013, embryo.asu.edu/pages/germ-layers. Accessed 9 June 2024.
Ruth. “Stem Cells | SL IB Biology Revision Notes 2025.” Save My Exams, 2024, www.savemyexams.com/dp/biology/sl/25/revision-notes/form-and-function/cell-specialisation/stem-cells/. Accessed 9 June 2024.
Vladislav Volarevic, et al. “Ethical and Safety Issues of Stem Cell-Based Therapy.” International Journal of Medical Sciences, vol. 15, no. 1, 1 Jan. 2018, pp. 36–45, www.ncbi.nlm.nih.gov/pmc/articles/PMC5765738/., https://doi.org/10.7150/ijms.21666. Accessed 9 June 2024.
Song, Won Kyung et al. “Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients.” Stem cell reports vol. 4,5 (2015): 860-72. doi:10.1016/j.stemcr.2015.04.005.
“Stem Cells.” Bioninja.com.au, 2024, ib.bioninja.com.au/stem-cells/#. Accessed 10 June 2024.