Is Stem Cell a Curer or an Obstruction?

Siska Darmayanti, Rina Triana, Angliana Chouw, Nurrani Mustika Dewi


Stem cell research and therapy are progressing these days dramatically. Stem cell therapy holds enormous treatment potential for many diseases which currently have no or limited therapeutic options. Unfortunately, this potential also comes with side-effects. In this review, the positive and negative effects of regulation of stem cells will be explained. Stem cells are undifferentiated cells which able to develop into many different cells of types in the body during early life and growth. There are five types of stem cells: embryonic stem cells, induced pluripotent stem cells, somatic stem cells, fetal stem cells and mesenchymal stem cells. Stem cell transplantation is one form of stem cell therapy, it comes with different techniques sourced, and those are autologous and allogeneic transplantation stem cells. In an autologous transplant, a patient's blood-forming stem cells are collected, meanwhile, in an allogeneic transplant, target cells are replaced with new stem cells obtained from a donor or donated umbilical cord blood. Its abilities to maintain the phenotype, self-renewing and differentiate itself into specialized cells, give rise to stem cell as an innovation for the treatment of various diseases. In the clinical setting, stem cells are being explored for different conditions, such as in tissue repair and regeneration and autoimmune diseases therapy. But along with its benefit, stem cell therapy also holds some harm. It is known that the treatment using stem cell for curing and rehabilitation has the risk of tumor formation.

Keywords: stem cell, therapy, transplantation, tumorigenic, mesenchymal stem cell, allogeneic

Full Text:



Joseph NM, Morrison SJ. Toward an understanding of the physiological function of mammalian stem cells. Dev Cell. 2005; 9(2): 173-83. CrossRef

Herberts CA, Kwa MS, Hermsen HP. Risk factors in the development of stem cell therapy. J Transl Med. 2011; 9(1): 29. doi: 10.1186/1479-5876-9-29. CrossRef

Master Z, McLeod M, Mendez I. Benefits, risks and ethical considerations in translation of stem cell research to clinical applications in Parkinson's disease. J Med Ethics. 2007; 33(3): 169-73. CrossRef

Konstantinov IE. In search of Alexander A. Maximow: the man behind the unitarian theory of hematopoiesis. PerspectBiol Med. 2000; 43(2): 269-76. CrossRef

UpToDate [Internet]. WolterKluwers. In: Scadden DT, Raaijmakers M. Overview of Stem Cells. [updated 2015; cited November 25, 2016]. Available from: Link

National Institutes of Health [Internet]. Bethesda: National Institutes of Health, U.S. Department of Health and Human Services. Stem Cell Information Home Page. [updated 2016; cite November 25, 2016]. Available from: Link

The University of Rodhe Island [Internet]. Shihadeh H. History and Recent Advances of Stem Cell Biology and the Implications for Human Health. Senior Honors Projects. [updated 2015; cite November 25, 2016]. Available from: Link

Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981; 292(5819): 154-6. CrossRef

Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. ProcNatlAcadSci USA. 1981; 78: 7634-8. Link

Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391): 1145-7. CrossRef

Solter D. From teratocarcinomas to embryonic stem cells and beyond: A history of embryonic stem cell research. Nat Rev Genet. 2006; 7(4): 319-27. CrossRef

Lengner CJ. IPS cell technology in regenerative medicine. Ann NY Acad Sci. 2010; 1192: 38-44. CrossRef

Bradley A, Evans M, Kaufman MH, Robertson E. Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature. 1984; 309(5965): 255-6. CrossRef

Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. Embryonic stem cell lines from human blastocysts: Somatic differentiation in vitro. Nat Biotechnol. 2000; 18(4): 399-404. CrossRef

Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007; 318(5858): 1917-20. CrossRef

Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007; 448(7151): 313-7. CrossRef

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007; 131(5): 861-72. CrossRef

Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, et al. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol. 2008; 26(11): 1276-84. CrossRef

Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008; 321(5893):1218-21. CrossRef

Hockemeyer D, Soldner F, Cook EG, Gao Q, Mitalipova M, Jaenisch R. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell. 2008; 3(3): 346-53. CrossRef

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4): 663-76. CrossRef

Yu J, Thomson JA. Pluripotent stem cell lines. Genes Dev. 2008; 22(15): 1987-97. CrossRef

Saric T, Hescheler J. Stem cells and nuclear reprogramming. Minim Invasive Ther Allied Technol. 2008; 17(2): 64-78. CrossRef

Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell. 2009; 137(4): 647-58. CrossRef

Meiliana A, Wijaya A. Progress and future challenges of human induced pluripotents stem cell in regenerative medicine. Indones Biomed J. 2011; 3(2): 76-92. CrossRef

Pessina A, Gribaldo L. The key role of adult stem cells: therapeutic perspectives. Curr Med Res Opin. 2006; 22(11): 2287-300. CrossRef

Koch P, Kokaia Z, Lindvall O, Brustle O. Emerging concepts in neural stem cell research: autologous repair and cell-based disease modelling. Lancet Neurol. 2009; 8(9): 819-29. CrossRef

Pappa KI, Anagnou NP. Novel sources of fetal stem cells: where do they fit on the developmental continuum?. Regen Med. 2009; 4(3): 423-33. CrossRef

De Coppi P, Bartsch G, Siddiqui MM, Xu T, Santos CC, Perin L, et al. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol. 2007; 25(1): 100-6. CrossRef

Prusa AR, Marton E, Rosner M, Bernaschek G, Hengstschläger M. Oct-4-expressing cells in human amniotic fluid: A new source for stem cell research? Hum Reprod. 2003; 18(7): 1489-93. Link

Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DO, et al. Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells. 2007; 25(2): 319-31. CrossRef

Meiliana A,Dewi NM, Wijaya A. Mesenchymal stem cells manage endogenous tissue regeneration. Indones Biomed J. 2016; 8(2): 71-90. CrossRef

Prockop DJ, Olson SD. Clinical trials with adult stem/progenitor cells for tissue repair: let's not overlook some essential precautions. Blood. 2007; 109(8): 3147-51. CrossRef

Kang SG, Shinojima N, Hossain A, Gumin J, Yong RL, Colman H, et al. Isolation and perivascular localization of mesenchymal stem cells from mouse brain. Neurosurgery. 2010; 67(3): 711-20. CrossRef

Najimi M, Khuu DN, Lysy PA, Jazouli N, Abarca J, Sempoux C, et al. Adult-derived human liver mesenchymal-like cells as a potential progenitor reservoir of hepatocytes?. Cell Transplant. 2007; 16(7): 717- 28. CrossRef

Lama VN, Smith L, Badri L, Flint A, Andrei AC, Murray S, et al. Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. J Clin Invest. 2007; 117(4): 989-96. CrossRef

Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells. 2004; 22(7): 1330-7. CrossRef

Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002; 13(12): 4279-95. CrossRef

Lina Y, Wijaya A. Novel sources of fetal stem cells for future regenerative medicine. Indones Biomed J. 2012; 4(1): 3-11. CrossRef

Lina Y, Wijaya A. Adipose-derived stem cells for future regenerative system medicine. Indones Biomed J. 2012; 4(2): 59-72. CrossRef

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284(5411): 143-7. CrossRef

Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002; 418(6893): 41-9. CrossRef

Memorial Sloan Kettering Cancer Center [Internet]. Blood & Marrow Stem Cell Transplantation: Transplantation at MSK. [updated 2016; cited November 25, 2016]. Available from: Link

Mamidi M, Dutta S, Bhonde R, Das A, Pal R. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: Which way to go? Med Hypotheses. 2014; 83(6): 787-91. CrossRef

Karantalis V, Schulman I, Balkan W, Hare JM. Allogeneic cell therapy: a new paradigm in therapeutics. Circ Res. 2014; 116(1): 12-15. CrossRef

Colpo GD, Ascoli BM, Wollenhaupt-Aguiar B, Pfaffenseller B, Silva EG, Cirne-Lima EO, et al. Mesenchymal stem cells for the treatment of neurodegenerative and psychiatric disorders. An Acad Bras Cienc. 2015; 87(2 Suppl): 1435-49. CrossRef

Jorgensen C, Noël D. Mesenchymal stem cells in osteoarticular diseases. Regen Med. 2011; 6(6 Suppl): 44-51. CrossRef

Pei X, Xi J, Yan X, Yue W, Zhou J. Mesenchymal stem cells in tissue repairing and regeneration: progress and future. Burns Trauma. 2013;1(1): 13-20. CrossRef

Eirin A, Lerman LO. Mesenchymal stem cell treatment for chronic renal failure. Stem Cell Res Ther. 2014; 5(4): 83. doi: 10.1186/scrt472. CrossRef

Zhao K, Liu Q. The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation. J Hematol Oncol. 2016; 9(1): 46. doi: 10.1186/s13045-016-0276-z. CrossRef

Zhao Q, Ren H, Han Z. Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases. J Cell Immunother. 2016; 2(1): 3-20. CrossRef

Pham PV. Clinical trials for stem cell transplantation: when are they needed? Stem Cell Res Ther. 2016; 7(1): 65. doi: 10.1186/s13287-016-0325-0. CrossRef

Kuruvilla J. The role of autologous and allogeneic stem cell transplantation in the management of indolent B-cell lymphoma. Blood. 2016; 127(17): 2093-98. CrossRef

Rigol M, Solanes N, Roura S, Roqué M, Novensà L, Dantas AP, et al. Allogeneic adipose stem cell therapy in acute myocardial infarction. Eur J Clin Invest. 2013; 44(1): 83-92. CrossRef

Barry FP, Murphy JM, O'Brien T, Mahon B. Mesenchymal stem cell transplantation for tissue repair. Semin Plast Surg. 2005; 19(3): 229-39. CrossRef

Dimarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Front Immunol. 2013; 4: 201. CrossRef

Kim N, Cho SG. Clinical applications of mesenchymal stem cells. Korean J Intern Med. 2016; 28(4): 387-402. CrossRef

Vonk LA, de Windt TS, Slaper-Cortenbach ICM, Saris DBF. Autologous, allogeneic, induced pluripotent stem cell or a combination stem cell therapy? Where are we headed in cartilage repair and why: a concise review. Stem Cell Res Ther. 2015; 6(1): 94. doi: 10.1186/s13287-015-0086-1. CrossRef

Wyles CC, Houdek MT, Behfar A, Sierra RJ. Mesenchymal stem cell therapy for osteoarthritis: current perspectives. Stem Cells Cloning. 2016; 8: 117-24. CrossRef

Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy – a review. BMC Musculoskelet Disord. 2016; 17(1): 230. doi: 10.1186/s12891-016-1085-9. CrossRef

Uth K, Trifonov D. Stem cell application for osteoarthritis in the knee joint: a mini review. World J Stem Cells. 2014; 6(5): 629-36. CrossRef

Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015; 17(1): 11-22. CrossRef

Wang L, Ting C, Yen M, Liu K, Sytwu H, Wu K, et al. Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials. J Biomed Sci. 2016; 23(1): 76. doi: 10.1186/s12929-016-0289-5. CrossRef

Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 2016; 7(1): e2062. doi: 10.1038/cddis.2015.327. CrossRef

Kalodimou VE. Regenerative medicine applications in autoimmune disorders. J Autoimmune Disord. 2015; 1(1): 8. Link

Kuhn NZ, Tuan RS. Regulation of stemness and stem cell niche of mesenchymal stem cells: Implications in tumorigenesis and metastasis. J Cell Physiol. 2010; 222(2): 268-77. CrossRef

Martinez-Agosto JA, Mikkola HK, Hartenstein V, Banerjee U. The hematopoietic stem cell and its niche: a comparative view. Genes Dev. 2007; 21(23): 3044-60. CrossRef

Scadden DT. The stem-cell niche as an entity of action. Nature. 2006; 441(7097): 1075-9. CrossRef

Zhang J, Li L. Stem cell niche: microenvironment and beyond. J Biol Chem. 2008; 283(15): 9499-503. CrossRef

He S, Nakada D, Morrison SJ. Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol. 2009; 25(1): 377-406. CrossRef

Nat Rep Stem Cells Online [Internet]. Mullard A. Proliferation without differentiation [updated 2008; cited December 2, 2016]. Available from: Link

Pauklin S, Vallier L. The cell-cycle state of stem cells determines cell fate propensity. Cell. 2013; 155(1): 135-47. CrossRef

Tsai RYL, McKay RD. A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes Dev. 2002; 16(23): 2991-3003. CrossRef

Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008; 27(41): 5497-510. CrossRef

Gilson E, Géli V. How telomeres are replicated. Nat Rev Mol Cell Biol. 2007; 8(10): 825-38. CrossRef

Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 2007; 447(7145): 725-9. CrossRef

Lambrou GI, Remboutsika E. Proliferation versus regeneration: the good, the bad and the ugly. Front Physiol. 2014; 5: 10. doi: 10.3389/fphys.2014.00010. CrossRef

Sandhaanam SD, Pathalam G, Dorairaj S, Savariar V. Mesenchymal stem cells (MSC): identification, proliferation and differentiation. Peer J PrePrints. 2013; 1: e148v1. doi: 10.7287/peerj.preprints.148v1. CrossRef

Zhang J, Huang X, Wang H, Liu X, Zhang T, Wang Y, et al. The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy. Stem Cell Res Ther. 2015; 6: 234. doi: 10.1186/s13287-015-0240-9. CrossRef

Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood. 2003; 102(10): 3837-44. CrossRef

Dittmar T, Seidel J, Zaenker KS, Niggemann B. Carcinogenesis driven by bone marrow-derived stem cells. Contrib Microbiol. 2006; 13: 156-69. CrossRef

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause DS, et al. Minimal criteria for defining multipotentmesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4): 315-7. CrossRef

Koltsova AM, Zenin VV, Yakovleva TK, Poljanskaya GG. Characterization of a novel mesenchymal stem cell line derived from human embryonic stem cells. Cell Tissue Biol. 2016; 10(1): 1-9. CrossRef

Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res. 2011; 109(8): 923-40. CrossRef

Piscaglia AC. Stem cells, a two-edged sword: risks and potentials of regenerative medicine. World J Gastroenterol. 2008; 14(27): 4273. doi: 10.3748/wjg.14.4273. CrossRef

Marsafy SE, Larghero J, Bennaceur-Griscelli A, Turhan A. Mesenchymal stem cells: pivotal players in hematopoietic stem cell microenvironment. J Stem Cell Res Ther. 2014; 4: 225. doi: 10.4172/2157-7633.1000225. CrossRef

Ame-Thomas P, Maby-El Hajjami H, Monvoisin C, Jean R, Monnier D, Caulet-Maugendre S, et al. Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis. Blood. 2007; 109(2): 693-702. CrossRef

Gao H, Priebe W, Glod J, Banerjee D. Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium. Stem Cells. 2009; 27: 857-65. CrossRef


Copyright (c) 2017 Cell and BioPharmaceutical Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Indexed by:



Cell and BioPharmaceutical Institute