Ethical and Safety Issues of Stem Cell-Based Therapy

Overview

Journal Int J Med Sci

Specialty General Medicine

Date 2018 Jan 16

PMID 29333086

Citations 349

Authors

Vladislav Volarevic

Bojana Simovic Markovic

Marina Gazdic

Ana Volarevic

Nemanja Jovicic

Nebojsa Arsenijevic

Lyle Armstrong

Valentin Djonov

Majlinda Lako

Miodrag Stojkovic

Affiliations

Soon will be listed here.

Abstract

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

Citing Articles

Advancements in osteoblast sourcing, isolation, and characterization for dental tissue regeneration: a review.

Venkataiah V, Mehta D, Fareed M, Karobari M Biomed Eng Online. 2025; 24(1):31.

PMID: 40057736 PMC: 11890725. DOI: 10.1186/s12938-025-01363-y.

Mesenchymal stromal/stem cells from perinatal sources: biological facts, molecular biomarkers, and therapeutic promises.

Allouh M, Rizvi S, Alamri A, Jimoh Y, Aouda S, Ouda Z Stem Cell Res Ther. 2025; 16(1):127.

PMID: 40055783 PMC: 11889844. DOI: 10.1186/s13287-025-04254-0.

Isolated Mitochondrial Transplantation as a Novel Treatment for Corneal Chemical Burns.

Jiang D, Yu J, Wu X, Yu X, Jin P, Zheng H Invest Ophthalmol Vis Sci. 2025; 66(3):14.

PMID: 40048188 PMC: 11895849. DOI: 10.1167/iovs.66.3.14.

Fetal adnexa-derived allogeneic mesenchymal stem cells for cardiac regeneration: the future trend of cell-based therapy for age-related adverse conditions.

Gorjipour F, Bohloolighashghaei S, Sotoudeheian M, Pazoki Toroudi H Hum Cell. 2025; 38(2):61.

PMID: 39998714 DOI: 10.1007/s13577-025-01190-2.

Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function.

Qin Y, Chen X, Bao L, Ren L, Dou G, Lian J J Nanobiotechnology. 2025; 23(1):106.

PMID: 39939963 PMC: 11823102. DOI: 10.1186/s12951-025-03194-4.

References

Duijvestein M, Vos A, Roelofs H, Wildenberg M, Wendrich B, Verspaget H . Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study. Gut. 2010; 59(12):1662-9. DOI: 10.1136/gut.2010.215152. View

Morandi F, Raffaghello L, Bianchi G, Meloni F, Salis A, Millo E . Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T-cell responses against viral or tumor-associated antigens. Stem Cells. 2008; 26(5):1275-87. PMC: 2726787. DOI: 10.1634/stemcells.2007-0878. View

Liang G, Zhang Y . Genetic and epigenetic variations in iPSCs: potential causes and implications for application. Cell Stem Cell. 2013; 13(2):149-59. PMC: 3760008. DOI: 10.1016/j.stem.2013.07.001. View

Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K . Induced pluripotent stem cells generated without viral integration. Science. 2008; 322(5903):945-9. PMC: 3987909. DOI: 10.1126/science.1162494. View

Gore A, Li Z, Fung H, Young J, Agarwal S, Antosiewicz-Bourget J . Somatic coding mutations in human induced pluripotent stem cells. Nature. 2011; 471(7336):63-7. PMC: 3074107. DOI: 10.1038/nature09805. View

Peng L, Xie D, Lin B, Liu J, Zhu H, Xie C . Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. Hepatology. 2011; 54(3):820-8. DOI: 10.1002/hep.24434. View

Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J . Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol. 2012; 27 Suppl 2:112-20. DOI: 10.1111/j.1440-1746.2011.07024.x. View

Mandai M, Watanabe A, Kurimoto Y, Hirami Y, Morinaga C, Daimon T . Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration. N Engl J Med. 2017; 376(11):1038-1046. DOI: 10.1056/NEJMoa1608368. View

Song W, Park K, Kim H, Lee J, Choi J, Chong S . Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients. Stem Cell Reports. 2015; 4(5):860-72. PMC: 4437471. DOI: 10.1016/j.stemcr.2015.04.005. View

10.

Blasco M, Serrano M, Fernandez-Capetillo O . Genomic instability in iPS: time for a break. EMBO J. 2011; 30(6):991-3. PMC: 3061043. DOI: 10.1038/emboj.2011.50. View

11.

Godfrey K, Mathew B, Bulman J, Shah O, Clement S, Gallicano G . Stem cell-based treatments for Type 1 diabetes mellitus: bone marrow, embryonic, hepatic, pancreatic and induced pluripotent stem cells. Diabet Med. 2011; 29(1):14-23. DOI: 10.1111/j.1464-5491.2011.03433.x. View

12.

Kuriyan A, Albini T, Townsend J, Rodriguez M, Pandya H, Leonard 2nd R . Vision Loss after Intravitreal Injection of Autologous "Stem Cells" for AMD. N Engl J Med. 2017; 376(11):1047-1053. PMC: 5551890. DOI: 10.1056/NEJMoa1609583. View

13.

Ciccocioppo R, Bernardo M, Sgarella A, Maccario R, Avanzini M, Ubezio C . Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease. Gut. 2011; 60(6):788-98. DOI: 10.1136/gut.2010.214841. View

14.

Feng B, Ng J, Heng J, Ng H . Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells. Cell Stem Cell. 2009; 4(4):301-12. DOI: 10.1016/j.stem.2009.03.005. View

15.

Khakoo A, Pati S, Anderson S, Reid W, Elshal M, Rovira I . Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma. J Exp Med. 2006; 203(5):1235-47. PMC: 2121206. DOI: 10.1084/jem.20051921. View

16.

Lazennec G, Jorgensen C . Concise review: adult multipotent stromal cells and cancer: risk or benefit?. Stem Cells. 2008; 26(6):1387-94. PMC: 2572832. DOI: 10.1634/stemcells.2007-1006. View

17.

Smith A . Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol. 2001; 17:435-62. DOI: 10.1146/annurev.cellbio.17.1.435. View

18.

Ljujic B, Milovanovic M, Volarevic V, Murray B, Bugarski D, Przyborski S . Human mesenchymal stem cells creating an immunosuppressive environment and promote breast cancer in mice. Sci Rep. 2013; 3:2298. PMC: 3725512. DOI: 10.1038/srep02298. View

19.

Cho Y, Lee W, Park K, Kim M, Yoo H, Yu C . Autologous adipose tissue-derived stem cells for the treatment of Crohn's fistula: a phase I clinical study. Cell Transplant. 2012; 22(2):279-85. DOI: 10.3727/096368912X656045. View

20.

Woltjen K, Michael I, Mohseni P, Desai R, Mileikovsky M, Hamalainen R . piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature. 2009; 458(7239):766-70. PMC: 3758996. DOI: 10.1038/nature07863. View