Stem Cell Cloning in Therapeutic Settings

Ryan Elsebai

English 21003

May 1, 2025

 

Stem cell research and therapeutic cloning represent some of the most promising frontiers in modern biomedical science. These technologies offer the potential to revolutionize treatments for degenerative diseases, organ failure, and genetic disorders by regenerating damaged tissues and creating patient-specific therapies. Central to their promise is the ability of certain stem cells to differentiate into any cell type, and the use of cloning methods like somatic cell nuclear transfer (SCNT) to generate genetically identical tissues. However, despite remarkable scientific advancements, therapeutic cloning has not yet achieved widespread clinical adoption. This is largely due to persistent scientific challenges and deeply rooted ethical controversies. Addressing these limitations is critical for the responsible advancement of stem cell-based therapies.

While the theoretical advantages of therapeutic cloning are considerable, significant scientific barriers hinder its broader application. One key issue is the biological complexity of creating stable and functional stem cell lines. Research by Mummery and Roelen (2013) outlines how SCNT-derived human embryonic stem cells (hESCs) may offer superior regenerative capabilities compared to induced pluripotent stem cells (iPSCs). However, they highlight a critical complication: the presence of mitochondrial DNA from the egg donor, even after nuclear transfer. This mitochondrial genetic variance, although minor, can influence the behavior and functionality of cloned cells, complicating their therapeutic use.

BRCA1 is a critical gene involved in the repair of DNA double-strand breaks through homologous recombination, an essential mechanism for maintaining genomic stability. Its significance lies in its dual role in both mitotic and meiotic cells, where it helps prevent mutations that can lead to cancer or reproductive failure. Mutations in BRCA1 are strongly associated with inherited breast and ovarian cancers, highlighting its role as a tumor suppressor. Beyond cancer, BRCA1 also plays a specialized role in meiosis, contributing to the accurate repair of DNA in germ cells and ensuring proper chromosome segregation during reproduction. The role of BRCA1 in DNA repair is well established in mitotic cells, but its function during meiosis remains less clear. 

In a detailed study published by Petalcorin et al. (2006), the BRCA1 orthologue in Caenorhabditis elegans (brc-1) was analyzed to understand its role during meiotic prophase. While brc-1 mutants in C. elegans were viable and capable of normal crossover recombination, as evidenced by the presence of six bivalents in diakinesis, they exhibited increased apoptosis and abnormal persistence of RAD-51 foci. These abnormalities suggest defects in DNA double-strand break (DSB) repair specific to meiosis, rather than errors in premeiotic DNA replication. When DSB formation was genetically inhibited by removing SPO-11 function, these defects disappeared, confirming their meiotic origin. This finding reveals a significant limitation in our understanding of BRCA1’s full biological role, especially in the context of germline stability and fertility. 

While homologous recombination is a high-fidelity repair mechanism, its successful execution depends on multiple proteins that direct repair either through crossover between homologues or non-crossover pathways involving sister chromatids. In the absence of brc-1, alternative repair strategies appear insufficient, leading to chromosome fragmentation in mutants that are already deficient in homologous chromosome recombination, such as him-14/MSH4 and syp-2. These observations emphasize the redundancy of repair pathways in meiotic cells and suggest that BRCA1’s role in maintaining genomic stability during gametogenesis may be more nuanced than previously thought. Understanding this complexity is essential, as failures in these processes can result in aneuploidy, infertility, or embryonic lethality—further linking defective DSB repair with heritable disease risk and cancer susceptibility.

Similarly, studies such as those conducted by Inagaki et al. (2025) emphasize that even advanced stem cell technologies, like vascularized organoids, face biological hurdles. Traditional organoid models suffer from poor oxygen and nutrient diffusion, leading to tissue degradation at their core. Although vascularization techniques have improved the viability of these models, replicating complex, fully functional human tissues remains a formidable challenge. Another major technical limitation relates to the scalability and genetic stability of stem cell lines. Li et al. (2022) introduced microfluidics-based cell sorting combined with the CEPT small-molecule cocktail to enhance the survival and consistency of human pluripotent stem cells (hPSCs). Their innovations address problems like high cell loss and variability between cell lines, which have historically limited the reliability of stem cell research. Still, even with improved protocols, ensuring the consistent production of genetically stable, therapeutically viable cells on a large scale remains a daunting task.

Moreover, Gura (2013) describes the work of Shoukhrat Mitalipov’s team, which succeeded in cloning human embryonic stem cells via SCNT. Their research demonstrated the creation of genetically stable stem cells closely resembling natural embryonic cells. Nevertheless, the high cost and intricate regulations surrounding SCNT significantly hamper its practical application, especially when compared to the relatively easier generation of iPSCs. From mitochondrial DNA challenges to scalability and cost barriers, the scientific obstacles facing therapeutic cloning are substantial and multifaceted. Another major challenge in therapeutic cloning is the technical inefficiency of somatic cell nuclear transfer (SCNT) itself. The procedure requires precise timing, skilled manipulation, and often results in low success rates, with many attempts yielding non viable embryos for stem cells with abnormalities. These inefficiencies not only increase the cost but also raise concerns about reproducibility and consistency. Furthermore, the use of human eggs in SCNT raises ethical and logistical issues, as egg retrieval is invasive and limited in supply, making large-scale production impractical.

Additionally, even when SCNT-derived stem cells are successfully created, their integration into therapeutic contexts remains limited by immune system responses and long-term safety uncertainties. Although these cells are genetically matched to the donor nucleus, differences in mitochondrial DNA can still provoke immune reactions or lead to dysfunction. Moreover, the long-term behavior of these cloned stem cells in the human body is not fully understood, particularly with respect to tumor formation or unintended differentiation. As a result, despite promising scientific breakthroughs, therapeutic cloning remains a highly experimental technique with considerable hurdles before it can become a mainstream medical treatment.

Beyond scientific hurdles, ethical concerns are perhaps the most significant impediment to the widespread adoption of therapeutic cloning. Central to these debates is the moral status of the cloned embryos used to derive stem cells. Many bioethicists and policymakers question whether creating embryos solely for research or therapeutic purposes is morally acceptable. Mummery and Roelen (2013) note that unlike iPSCs, which can be derived from adult cells without the need for embryos, SCNT necessarily involves the creation and destruction of embryos. For many, this raises profound ethical concerns about the sanctity of human life at its earliest stages. Public policy has reflected these concerns. Gura (2013) highlights how institutions like the National Institutes of Health and the California Institute for Regenerative Medicine impose tight regulations on cloning research, partly due to ethical objections. These restrictions limit funding, slow research progress, and create an uneven global landscape where scientific potential is curtailed by societal values.

According to the Uehiro Oxford Institute (n.d.), therapeutic cloning, which involves creating stem cells, tissue, or organs genetically matched to a patient, offers the significant advantage of minimizing tissue rejection. However, this process requires the creation and subsequent destruction of a human embryo, an act that raises moral objections depending on one’s view of the embryo’s moral status. As the article explains, while embryonic stem cells are pluripotent and can transform into any cell type, their use is restricted due to the moral controversy tied to their source: embryos often left over from IVF treatments. Non-embryonic alternatives, such as cord-blood stem cells or induced pluripotent stem cells (iPSCs), are less ethically problematic but lack the full versatility of embryonic stem cells and offer limited insight into early human development. Moreover, the article notes that research using admixed embryos like cybrids introduces further ethical concerns regarding the dignity and identity of such organisms. These limitations highlight why stem cell cloning, despite its potential, remains largely experimental and is not yet a standard therapeutic option.

Another important limitation highlighted by the Uehiro Oxford Institute (n.d.) is the challenge of public perception and regulatory barriers, which further slow the development of stem cell cloning therapies. The controversial nature of creating embryos for research, particularly when human and animal genetic material is combined leads to public unease and political resistance. Objections often center on the belief that such research “interferes with nature” or diminishes the dignity of human life. This societal discomfort influences policy making and can result in restrictive laws or lack of funding for stem cell cloning research. Without broad public and legislative support, the translation of cloning technologies from the lab to clinical settings remains limited, despite their theoretical potential. These sociopolitical and ethical constraints must be addressed alongside scientific challenges for stem cell cloning to become a viable therapeutic tool.

There are broader fears about the slippery slope of cloning technology. Some worry that advances in therapeutic cloning could eventually lead to reproductive cloning, creating full human clones, which raises a host of additional ethical, legal, and social dilemmas. While therapeutic and reproductive cloning are distinct, public perception often conflates the two, further complicating regulatory efforts and fueling opposition. Furthermore, the commodification of human eggs for cloning raises additional ethical issues. Since SCNT requires donated eggs, there are concerns about the exploitation of women, especially in vulnerable populations, who may be pressured into donating eggs under financial incentives. Expanding on these concerns, the potential misuse of cloning technologies amplifies the urgency for clear ethical boundaries and transparent regulation. Without strict oversight, the line between therapeutic and reproductive cloning could blur in practice, especially as technological capabilities advance. This ambiguity risks undermining public trust in legitimate scientific research and may stall progress in regenerative medicine due to fear-driven opposition. Moreover, ambiguous or inconsistent international laws make it difficult to enforce ethical standards, leading to concerns about “science tourism,” where researchers or patients seek cloning services in countries with looser regulations.

If cloning technologies become commercialized, there is a risk of creating a market where access to treatment is determined by socioeconomic status, further deepening health inequities. The financial incentives tied to egg donation could disproportionately affect low-income women, potentially reducing informed consent to a transactional decision made under economic duress. These factors highlight the need for not only scientific scrutiny but also robust ethical frameworks that prioritize human dignity, consent, and equitable access.

Altogether, these ethical controversies have created a cautious and heavily regulated environment that significantly slows the translation of therapeutic cloning research into widespread clinical practice. Despite the considerable obstacles, ongoing scientific innovations offer reasons for cautious optimism. Research by Inagaki et al. (2025) on vascularized organoids demonstrates meaningful progress in overcoming biological limitations by improving tissue viability through enhanced oxygen and nutrient diffusion. These breakthroughs in cloning could pave the way for creating transplantable tissues that are more functional and useful in clinical settings. Similarly, the microfluidics-based sorting method introduced by Li et al. (2022) addresses major issues of variability and scalability in hPSC research. By standardizing the creation of stable clonal lines, this approach improves reproducibility and lowers costs, moving the field closer to feasible therapeutic applications. Meanwhile, Mitalipov’s SCNT-derived hESCs, as described by Gura (2013), reveal that it is technically possible to produce stable, genetically accurate stem cell lines. If the high costs and regulatory barriers can be addressed, SCNT could still play a vital role in regenerative medicine. 

Nonetheless, scientific innovation alone is unlikely to resolve the ethical dilemmas surrounding therapeutic cloning. Broader societal dialogue and policy development will be necessary to establish ethical frameworks that both protect moral concerns and support scientific advancement. International cooperation and public engagement are crucial to creating guidelines that balance innovation with respect for fundamental ethical principles. The Uehiro Oxford Institute underscores the ethical complexities surrounding therapeutic cloning, particularly the moral status of embryos created and destroyed during the process. While therapeutic cloning offers the advantage of producing genetically matched tissues, thereby minimizing the risk of rejection, it necessitates the creation and subsequent destruction of embryos, a practice that raises significant moral concerns for many. The Institute also explores the use of admixed human embryos, such as cybrids, which involve combining human and animal genetic material. These entities are instrumental in research aimed at understanding human development but are often met with objections rooted in notions of human dignity and natural order. Such ethical debates highlight the challenges in advancing therapeutic cloning technologies while respecting diverse moral perspectives.​

Stem cell cloning through techniques like SCNT holds immense promise for revolutionizing regenerative medicine and addressing critical health challenges. Yet, its success remains hindered by profound scientific limitations, including biological complexity, scalability issues, and financial burdens, as well as by enduring ethical concerns regarding the moral status of cloned embryos and the risks of exploitation. While advances in vascularized organoids, microfluidic sorting, and cloning stability suggest that many technical barriers are slowly being overcome, ethical debates continue to restrict the field’s expansion. The future of therapeutic cloning will depend not only on solving scientific problems but also on fostering ethical consensus and developing regulatory frameworks that encourage responsible innovation. By understanding and addressing these principal limitations, the field of stem cell cloning can move closer to realizing its transformative potential in medicine.

 

References

Gura, T. (2013). Cell biology: Does cloning produce better embryonic stem cells? Science, 340(6139), 1390. https://pubmed.ncbi.nlm.nih.gov/23788774/

Inagaki, S., Nakamura, S., Kuse, Y., Aoshima, K., Funato, M., Shimazawa, M., & Hara, H. (2025). Establishment of vascularized human retinal organoids from induced pluripotent stem cells. Stem Cells. Advance online publication. https://doi.org/10.1093/stmcls/sxae093

Li, Y., Guo, X., Tang, K., & Liu, C. (2022). Efficient and safe single-cell cloning of human pluripotent stem cells using microfluidics-based cell sorting. Nature Protocols. Advance online publication. https://pubmed.ncbi.nlm.nih.gov/36261632/

Mummery, C. L., & Roelen, B. A. J. (2013). Cloning human embryos. Nature, 498(7453), 174–175. https://doi.org/10.1038/498174a

Mummery, C., & Roelen, B. (2008). Stem cells: Science, ethics, and politics. EMBO Reports, 9(2), 105–110. https://doi.org/10.1038/sj.embor.7401167

Uehiro Oxford Institute. (n.d.). Cloning and stem cell. University of Oxford. https://www.uehiro.ox.ac.uk/cloning-and-stem-cell