by Gabriela Blaszczyk

Graphic design by Qingyue Guo

In an ideal world, there would not be thousands of people dying each year waiting for an organ transplant. In this ideal world, couples would not struggle with navigating the journey of infertility challenges. What potential solutions do both scenarios have in common? Human embryonic stem cells.

One needs to be careful with the exact definition of a stem cell. In popular culture, this is an umbrella term used to describe novel fad treatments to retain that “youthful glow”,  or more bleakly, a strategy predatory companies use for selling a supposed “cure” for a debilitating disease that has not yet been rigorously tested. Biologically, a stem cell has the potential to generate multiple cell types in the body and self-renew indefinitely. However, there are various types of stem cells, each having different capacity. The stem cells found in a developing embryo are pluripotent, meaning they are unrestricted in their developmental potential. Stem cells found in the adult body, such as cells found in your blood or your brain, are restricted to becoming a defined cell type and serve the purpose of repairing an organ in case of damage, and these are multipotent.¹

Since embryonic stem cells (ESCs) can generate any cell type in the body, ESC research has proven beneficial in the fields of human fertility and development, drug discovery (by supplying human cells for testing, circumventing the need for human experimentation), transplantation therapy, and even in clinical trials to alleviate deficits following spinal cord injury.² ESCs have been used for research from both human³ and rodent sources^4,5 for over 30 years. These cells are harvested from leftover in vitro fertilization procedures and are kept in culture for further use. From there, they can be used indefinitely, generating a cell line. However, despite the promise of ESCs, there are legal and moral dilemmas to navigate, as well as several misconceptions, when it comes to effectively utilizing human embryonic material.

Current public misconceptions may have the potential to harm the scientific progress of human stem cell research, resulting in a reduction or complete ban of human stem cells.⁶ The primary concern of the public is that human embryos are destroyed every time a research lab requires access to ESCs. While ethically controversial, this is a misconception, as researchers use the same ESC lines for several decades, which were generated in the early years of ESC research. The International Society for Stem Cell Research (ISSCR) is the main international governing body and provides guidelines on the use of human stem cells for academic research purposes. The ISSCR states that “all [forms of embryonic] research should have a compelling scientific rationale and necessitate the use of these materials rather than employ alternative models. The research should use the minimum number of embryos necessary to achieve the scientific objective”.⁷ Whether in a fertility clinic or in the lab, human embryos can only be kept in culture for 14 days (known as the 14-day rule), and this is governed into law in several countries. Further, human embryos or synthetic material resembling human embryos cannot be implanted into a mammalian uterus under any circumstance.⁷ While there are regulatory guidelines outlining ESC use, public misconceptions about human ESC research undermine the scientific potential and impact of the findings.

Another current debate concerns the relevance of the 14-day rule. Scientists have never been able to observe the discrete developmental steps occurring between the 14- and 28-day period post-fertilization, and our knowledge of this time in human development is extrapolated from animal models. This is also known as the “black box” of human development. Mice are the most common model for comparison, however there are significant differences in development, namely their gestation period only being 21 days. This time frame is when many genetic and developmental disorders develop, as well as when many pregnancies fail,⁸ therefore with more studies into this developmental timepoint, there is the chance to help many individuals.

Are there reasonable alternatives? Induced pluripotent stem cells (iPSCs) are derived from any cell in the adult organism (most commonly from non-invasive tissues such as blood, skin, or urine) and are synthetically reverted to an embryonic-like state.⁹ These have been shown to mimic ESCs, and there have been many methods describing their use in the generation of various cells for study, and even embryo-like structures. One key difference with iPSCs is that they do not have the capacity to form a human fetus. Beyond generating iPSCs, there are many discrete signatures and steps that simply cannot be replicated in a dish, rendering them nonviable (due to acquired damage, and residual “memory” of the adult cell type). This begs the question: are there still reasonable instances where human embryos need to be used to answer a research question where an alternative, such as human iPSCs, will not suffice? iPSCs mimic ESCs biologically and even surpass their utility in instances such as transplantation or modelling genetic disorders. We can generate cells from iPSCs to use on the same patient and circumvent the need for matching with a different donor, or needs for genetic editing. However, there are still concerns on whether these cell types equal on a genetic level.¹⁰

The use of human embryonic material in research is easily misconstrued if the correct definitions are not used. A letter to the US President from congress argued for the cessation of government funding of human ESC research stating that adult stem cells (mostly mentioned to be sourced from bone marrow or umbilical cord blood) have been used to cure numerous disorders, and that transplantation therapies have not progressed quickly enough.⁶ However, they failed to acknowledge that these adult stem cells do not have the same pluripotent capacity as ESCs or iPSCs, and therefore cannot be used in the same manner for developmental research, regenerative therapies, or modelling disease in a human context.

To see progress in stem cell research, we will require an interdisciplinary approach. Basic researchers, engineers, and medical doctors will need to work together to develop new avenues for innovating the approaches we have today. While we need to keep in mind that no scientific models are perfect replicas of what occurs within an organism, but rather an approximation, we should also celebrate the strong translational potential of ESCs for more directly exploring diseases in ways not possible with human experimentation. As scientists, we can strive to educate our peers and present both strengths and limitations as well as realities of human ESCs in research.

References

1. Stem cell glossary. [Internet]. International Society for Stem Cell Research; 2024. [cited: 2025 May 5]. Available from: https://www.aboutstemcells.org/info/glossary

2. Fessler RG, Ehsanian R, Liu CY, et al. A phase 1/2a dose-escalation study of oligodendrocyte progenitor cells in individuals with subacute cervical spinal cord injury. J Neurosurg Spine. 2022;37(6):812-820. doi: 10.3171/2022.5.SPINE22167

3. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145-7. doi: 10.1126/science.282.5391.1145

4. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154-6. doi: 10.1038/292154a0

5. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981;78(12):7634-8. doi: 10.1073/pnas.78.12.7634

6. Smith, Chris. “Member letter to president trump on human embryonic stem cell research”. 04/07/2025. Congressman Chris Smith [chrissmith.house.gov]. Available from: https://chrissmith.house.gov/uploadedfiles/member_letter_to_president_trump_on_human_embryonic_stem_cell_research_april_7_2025.pdf

7. Lovell-Badge R, Anthony E, Barker RA, et al. ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update. Stem Cell Reports. 2021;16(6):1398-1408. doi: 10.1016/j.stemcr.2021.05.012

8. Williams K, Johnson MH. Adapting the 14-day rule for embryo research to encompass evolving technologies. Reprod Biomed Soc Online. 2020;10:1-9. doi: 10.1016/j.rbms.2019.12.002

9. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861-72. doi: 10.1016/j.cell.2007.11.019

10.  Chin MH, Mason MJ, Xie W, et al. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell. 2009;5(1):111-123. doi:10.1016/j.stem.2009.06.008