Comparison of Natural Multipotent Stem Cell and Induced Pluripotent Stem Cell Therapeutic Applications: Benefits and Challenges
Main Article Content
Abstract
Natural Multipotent Stem Cell preparation is unique and safe when compared with other methods. Using this technology, American Stem Cell Base Dr. Wang has treated more than 100 kinds of diseases, made thousands of transplantations, with excellent cure rate (> 90% cured or great improvement per clinical end point measurement) and most importantly, there are no significant side effects. In 2012, the Nobel Prize-winning medical technology, Induced Pluripotent Stem Cell, invigorated stem cell research as it showed that Induced Pluripotent Stem Cell has the potential to produce every type of cell and tissue in the body. However, the inherited properties of Induced Pluripotent Stem Cell were known as tumorigenicity, immunogenicity, and heterogeneity. In his 2024 review article, Dr. Yamanaka indicated that he had dedicated two decades of research aimed at overcoming these three difficulties. Given the potential for these cells to become cancerous stem cells, the widespread application of the technology in treating various clinical diseases might require collaborative research by scholars, scientists, and clinicians and potentially could take decades to resolve. Natural Multipotent Stem Cell, on the other hand, is a mature biotechnology with specialized technologies and capabilities for mass production. It has successfully treated over 100 long-standing and intractable diseases, potentially providing widespread relief to millions afflicted with these diseases. This study provided a side-by-side comparison of two leading and promising stem cell therapy candidates, natural Multipotent Stem Cell and Induced Pluripotent Stem Cell, in clinical applications and present the challenges and promises in stem cell therapy.
Article Details
How to Cite
WANG, Fu Nan et al.
Comparison of Natural Multipotent Stem Cell and Induced Pluripotent Stem Cell Therapeutic Applications: Benefits and Challenges.
Medical Research Archives, [S.l.], v. 13, n. 10, oct. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6936>. Date accessed: 06 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i10.6936.
Section
Case Reports
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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30. Gornalusse GG, Hirata RK, Funk SE, Riolobos L, Lopes VS, Manske G, Prunkard D, Colunga A, Hanafi L, Clegg DO, et al. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat. Biotechnol. 2017; 35:765-772
31. Koyanagi-Aoi M, Ohnuki M, Takahashi K, Okita K, Noma H, Sawamura Y, Teramoto I, Narita M, Sato Y, Ichisaka T, et al. Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells. Proc. Natl. Acad. Sci. USA. 2013; 110:20569-20574
32. Theunissen TW, Friedli M, He Y, Planet E, O'Neil RC, Markoulaki S, Pontis J, Wang H, Iouranova A, Imbeault M, et al. Molecular Criteria for Defining the Naive Human Pluripotent State. Cell Stem Cell. 2016; 19:502-515
33. Avior Y, Eggan K, Benvenisty N. Cancer-Related Mutations Identified in Primed and Naive Human Pluripotent Stem Cells. Cell Stem Cell. 2019; 25:456-461
34. Avior Y, Eggan K, Benvenisty N. Cancer-Related Mutations Identified in Primed and Naive Human Pluripotent Stem Cells. Cell Stem Cell. 2019; 25:456-461
35. Kamada M, Mitsui Y, Kumazaki T, Kawahara Y, Matsuo T, Takahashi T. Tumorigenic risk of human induced pluripotent stem cell explants cultured on mouse SNL76/7 feeder cells. Biochem Biophys Res Commun. 2014 Oct 24;453(3):668-73. doi: 10.1016/j.bbrc.2014.10.009. Epub 2014 Oct 8
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38. Simonson OE, Domogatskaya A, Volchkov P, Rodin S. The safety of human pluripotent stem cells in clinical treatment. Ann Med. 2015;47(5):370-80. doi: 10.3109/07853890.2015.1051579. Epub 2015 Jul 6.
39. Patel S, Athirasala A, Menezes P, Ashwanikuma A, Zou T, Sahay G, and Bertassoni L. Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine Applications. Tissue Eng Part A; 2019;25(1-2): 1-112
40. Maziarz A, Kocan B, Bester M, Budzik S, Cholewa M, Ochiya T and Banas A. How electromagnetic fields can influence adult stem cells: positive and negative impact. Stem cell Research and Therapy 2016 7, Article 54
41. Wang FN, Ed, American Stem Cell Medicine Ace Review. Chapter 1, Section 7 pp91-101, Clinical Application, pp. 369-436, Book Series of The World Medical Health Organization of The United Nations. American Stem Cell Base, Publisher, United States, 2024; ISBN 979-8-218-97499-2
2. Rippon HJ, and Bishop AE. Embryonic stem cells. Cell Prolif. 2004; 37(1):22-23
3. Knoepfler PS. Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells. 200927 (5): 1050–6
4. Yamanaka S. Pluripotent Stem Cell-Based Cell Therapy-Promise and Challenges. Cell Stem Cell. 2020 Oct 1;27(4):523-531. doi: 10.1016/j.stem. 2020.09.014
5. Wang SG, Hsu, NC, Wang, SM, and Wang, FN. Successful Treatment of Plaque Psoriasis with Allogeneic Gingival Mesenchymal Stem Cells: A Case Study. Dermatol Medicine 2020: 1-4
6. Wang SG, Hsu, NC, Wang, SM, Hsu, MC and Wang, FN. First-in-human High Cumulative Dose Mesenchymal Stem Cell Therapy in Multiple Myelomas: A Case Report. J. Hematol. and Transfu. 2021 8(1):1090
7. Wang FN, Hsu MC, Wang SL, Wang SG, Chen WC, Lee TD, Wang SM, and Doong H. Stem cell therapy: A Possibility for Coronavirus. J. Hematol and Transfus.2021 8 (2):1094
8. Wang SG, Wang SM, Hsu MC, Wang FN. Mesenchymal stem cell treatment improves renal failure and multiple episodes of nephrolithiasis. Journal of Urology and Research. 2022 91(1):1130
9. Zhong C, Liu M, Pan X, Zhu A. Tumorigenicity risk of iPSCs in vivo: nip it in the bud. Precision Clinical Medicine, Volume 5, Issue 1, March 2022, pbac004
10. Drishty B. Sarker DB, Xu Y, Mahmud F, Jocelyn JA, and Sang QA. Interconversion of Cancer Cells and Induced Pluripotent Stem Cells. Cells 2024, 13(2), 125; doi.org/10.3390/cells13020125
11. Doss MX, Agapios Sachinidis A. Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications. Cells. 2019 Apr 30;8(5):403. doi: 10.3390/cells8050403
12. Shamsian A, Sahebnasagh R, Norouzy A, Hussein SH, Ghahremani MH, Azizi Z. Cancer cells as a new source of induced pluripotent stem cells. Stem Cell Res Ther. 2022 Sep 5;13:459. doi: 10.1186/s13287-022-03145-y
13. Peterson SE, Loring JF. Genomic instability in pluripotent stem cells: implications for clinical applications. J Biol Chem. 2014 Feb 21;289(8): 4578-84. doi: 10.1074/jbc.R113.516419. Epub 2013 Dec 20
14. Gore, A. Li, Z. Fung, HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I. Giorgetti A, Isreal MA, Kiskinis E, Lee J et al Somatic coding mutations in human induced pluripotent stem cells. Nature. 2011; 471:63-67
15. Orgueira, AM, Antelo, BR, Arias, JAD, Varela ND, Vence NA, Pereze MSG, Lopez JLB. Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome. Sci. Rep. 2020; 10:2407
16. Zhang J, Jia Z, Pan H, Ma W, Liu Y, Tian X, Han Y, Wang Q, Zhou C, Zhang C. From induced pluripotent stem cell (iPSC) to universal immune cells: literature review of advances in a new generation of tumor therapies. Transl Cancer Res. 2025 Apr 30;14(4): 2495-2507. doi: 10.21037/tcr-24-1087. Epub 2025 Apr 15
17. Jiang Y, Zhang L, Zhang F, Bi W, Zhang P, Yu X, Rao S, Wang S, Li Q, Ding C, Jin Y, Yang H. Dual human iPSC-derived cardiac lineage cell-seeding extracellular matrix patches promote regeneration and long-term repair of infarcted hearts. Bioact Mater. 2023 May 27:28:206-226. doi: 10.1016/j.bioactmat.2023.05.015. eCollection 2023 Oct
18. Soma T, Oie Y, Takayanagi H, Matsubara S, Yamada T, Nomura M, Yoshinaga Y, Maruyama K, Watanabe A, Takashima K, Mao Z, Quantock AJ, Hayashi R, Nishida K. Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan. Lancet. 2024 Nov 16;404(10466): 1929-1939. doi: 10.1016/S0140-6736(24)01764-1. Epub 2024 Nov 7
19. Raniga K, Nasir A, Vo NTN, Vaidyanathan R, Dickerson S, Hilcove S. Mosqueira D, Mirams GR, Clements P, Hicks R, Pointon A, Stebbeds W, Francis J, Denning C. Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes. Cell Stem Cell. 2024 Mar 7;31(3):292-311. doi: 10.1016/j.stem. 2024.01.007. Epub 2024 Feb 15
20. Wyles SP, Brandt EB, Nelson TJ. Stem Cells: The Pursuit of Genomic Stability. Int J Mol Sci. 2014;15(11):20948–20967. doi: 10.3390/ijms151120948
21. Panchalingam KM, Jung S, Rosenberg L, Leo A. Behie LA. Bioprocessing strategies for the large-scale production of human mesenchymal stem cells: a review. Stem Cell Research & Therapy (2015) 6:225. doi: 10.1186/s13287-015-0228-5
22. Mas-Bargues C, Sanz-Ros J, Román-Domínguez A, Inglés M, Gimeno-Mallench L, Alami ME, Viña-Almunia J, Gambini J, Viña J, Borrás C. Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine. Int J Mol Sci. 2019;20(5):1195. doi: 10.3390/ijms20051195
23. Kim D, Lee AE, Xu Q, Zhang Q, Le AD. Gingiva-Derived Mesenchymal Stem Cells: Potential Application in Tissue Engineering and Regenerative Medicine - A Comprehensive Review. Front Immunol. 2021 Apr 16:12:667221. doi: 10.3389/fimmu. 2021.667221. eCollection 2021
24. Kumar D, Tanwar R. World's first: stem cell therapy reverses diabetes. Stem Cell Res Ther. 2024 Dec 20;15(1):487. PMC11662597. doi: 10.1186/ s1328-024-04036-0
25. Doi D, Magotani H, Kikuchi T, Ikeda M, Hiramatsu S, Yoshida K, Amano N, Nomura M, Umekage M, Morizane A, Takahashi J. Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson's disease. Nat Commun. 2020 Jul 6;11(1):3369. doi: 10.1038/s41467-020-17165-w
26. Wenker SD, Leal MC, Farías MI, Zeng X, Pitossi FJ. Cell therapy for Parkinson's disease: Functional role of the host immune response on survival and differentiation of dopaminergic neuroblasts. Brain Res. 2016 May 1;1638(Pt A):15-29. doi: 10.1016/j.brainres.2015.06.054. Epub 2015 Aug 1
27. Mandai M, Watanabe A, Kurimoto Y, Mandai M, Watanabe A, Hirami Y, Daimon T, Fujihara M, Akimaru H, Sakai N, et al. Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration. N. Engl. J. Med. 2017; 376:1038-1046
28. Sugita S, Mandai M, Hirami Y, Takagi S , Maeda T, Fujihara M, Matsuzaki M, Yamamoto M, Iseki K, Hayashi N Hono A, et al. HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration. J. Clin. Med. 2020; 9:2217
29. Deuse T, Hu X, Agbor-Enoh S, Koch M, Spitzer MH, Gravina A, Alawi M, Marishta A, Peters B, Kosaloglu-Yalcin Z, et al. De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans. Nat. Biotechnol. 2019; 37:1137-1144
30. Gornalusse GG, Hirata RK, Funk SE, Riolobos L, Lopes VS, Manske G, Prunkard D, Colunga A, Hanafi L, Clegg DO, et al. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat. Biotechnol. 2017; 35:765-772
31. Koyanagi-Aoi M, Ohnuki M, Takahashi K, Okita K, Noma H, Sawamura Y, Teramoto I, Narita M, Sato Y, Ichisaka T, et al. Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells. Proc. Natl. Acad. Sci. USA. 2013; 110:20569-20574
32. Theunissen TW, Friedli M, He Y, Planet E, O'Neil RC, Markoulaki S, Pontis J, Wang H, Iouranova A, Imbeault M, et al. Molecular Criteria for Defining the Naive Human Pluripotent State. Cell Stem Cell. 2016; 19:502-515
33. Avior Y, Eggan K, Benvenisty N. Cancer-Related Mutations Identified in Primed and Naive Human Pluripotent Stem Cells. Cell Stem Cell. 2019; 25:456-461
34. Avior Y, Eggan K, Benvenisty N. Cancer-Related Mutations Identified in Primed and Naive Human Pluripotent Stem Cells. Cell Stem Cell. 2019; 25:456-461
35. Kamada M, Mitsui Y, Kumazaki T, Kawahara Y, Matsuo T, Takahashi T. Tumorigenic risk of human induced pluripotent stem cell explants cultured on mouse SNL76/7 feeder cells. Biochem Biophys Res Commun. 2014 Oct 24;453(3):668-73. doi: 10.1016/j.bbrc.2014.10.009. Epub 2014 Oct 8
36. Zou Y, Hui R, Song L, The era of clinical application of gene diagnosis in cardiovascular diseases is coming. Chronic Dis Transl Med. 2020; 5(4):214–220. doi: 10.1016/j.cdtm.2019.12.005
37. Mitrano TI, Grob MS, Carri F, Nova-Lamperti E, Luz PA, Fierro FS, Quintero A, Chaparro A, Sanz 48. Cirino AL, Harris S, Lakdawala NK, Michels M, Olivotto I, Day SM, Abrams DJ, Charron P, Caleshu C, Semsarian C, Ingles J, Rakowski H, Judge DP, Ho CY. Role of Genetic Testing in Inherited Cardiovascular Disease: A Review JAMA Cardiol. 2017;2(10):1153-1160. doi: 10.1001/jamacardio.2017.2352
38. Simonson OE, Domogatskaya A, Volchkov P, Rodin S. The safety of human pluripotent stem cells in clinical treatment. Ann Med. 2015;47(5):370-80. doi: 10.3109/07853890.2015.1051579. Epub 2015 Jul 6.
39. Patel S, Athirasala A, Menezes P, Ashwanikuma A, Zou T, Sahay G, and Bertassoni L. Messenger RNA Delivery for Tissue Engineering and Regenerative Medicine Applications. Tissue Eng Part A; 2019;25(1-2): 1-112
40. Maziarz A, Kocan B, Bester M, Budzik S, Cholewa M, Ochiya T and Banas A. How electromagnetic fields can influence adult stem cells: positive and negative impact. Stem cell Research and Therapy 2016 7, Article 54
41. Wang FN, Ed, American Stem Cell Medicine Ace Review. Chapter 1, Section 7 pp91-101, Clinical Application, pp. 369-436, Book Series of The World Medical Health Organization of The United Nations. American Stem Cell Base, Publisher, United States, 2024; ISBN 979-8-218-97499-2