본문 바로가기
KERD
논문KCI 등재

Usage of Human Mesenchymal Stem Cells in Cell-based Therapy: Advantages and Disadvantages

박정수|김희정
한국발생생물학회 (The Korea Society Of Developmental Biology)|2017.03|발생과 생식 (DEVELOPMENT & REPRODUCTION)|제21권 제1호|pp. 1-10

2

조회

0

다운로드

4

인용

0

참고문헌

키워드

Mesenchymal stem cellRegenerative medicineCellular senescenceCell-therapy
주제분류생물학

초록

The use of human mesenchymal stem cells (hMSCs) in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it shows applications to numerous incurable diseases. hMSCs show several superior properties for therapeutic use compared to other types of stem cells. Different cell types are discussed in terms of their advantages and disadvantages, with focus on the characteristics of hMSCs. hMSCs can proliferate readily and produce differentiated cells that can substitute for the targeted affected tissue. To maximize the therapeutic effects of hMSCs, a substantial number of these cells are essential, requiring extensive ex vivo cell expansion. However, hMSCs have a limited lifespan in an in vitro culture condition. The senescence of hMSCs is a double-edged sword from the viewpoint of clinical applications. Although their limited cell proliferation potency protects them from malignant transformation after transplantation, senescence can alter various cell functions including proliferation, differentiation, and migration, that are essential for their therapeutic efficacy. Numerous trials to overcome the limited lifespan of mesenchymal stem cells are discussed.

Abstract

The use of human mesenchymal stem cells (hMSCs) in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it shows applications to numerous incurable diseases. hMSCs show several superior properties for therapeutic use compared to other types of stem cells. Different cell types are discussed in terms of their advantages and disadvantages, with focus on the characteristics of hMSCs. hMSCs can proliferate readily and produce differentiated cells that can substitute for the targeted affected tissue. To maximize the therapeutic effects of hMSCs, a substantial number of these cells are essential, requiring extensive ex vivo cell expansion. However, hMSCs have a limited lifespan in an in vitro culture condition. The senescence of hMSCs is a double-edged sword from the viewpoint of clinical applications. Although their limited cell proliferation potency protects them from malignant transformation after transplantation, senescence can alter various cell functions including proliferation, differentiation, and migration, that are essential for their therapeutic efficacy. Numerous trials to overcome the limited lifespan of mesenchymal stem cells are discussed.

참고문헌 (61)

  1. Amps K, "Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage", Nat Biotechnol, 29, pp.1132~1144 (2011)
  2. Atoui R, "Mesenchymal stromal cells as universal donor cells", Expert Opin Biol Ther, 12, pp.1293~1297 (2012)
  3. Banfi A, "Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy", Exp Hematol, 28, pp.707~715 (2000)
  4. Boyle AJ, "Is stem cell therapy ready for patients? Stem cell therapy for cardiac repair. ready for the next step", Circulation, 114, pp.339~352 (2006)
  5. Bruder SP, "Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation", J Cell Biochem, 64, pp.278~294 (1997)
  6. Burova E, "Sublethal oxidative stress induces the premature senescence of human mesenchymal stem cells derived from endometrium", Oxid Med Cell Longev, 2013, pp.474931~ (2013)
  7. Carpenter L, "Efficient differentiation of human induced pluripotent stem cells generates cardiac cells that provide protection following myocardial infarction in the rat", Stem Cells Dev, 21, pp.977~986 (2012)
  8. Cheung AY, "Isolation of MECP2-null Rett Syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation", Hum Mol Genet, 20, pp.2103~2115 (2011)
  9. Chong PP, "Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells", J Orthop Res, 30, pp.634~642 (2012)
  10. Crisan M, "A perivascular origin for mesenchymal stem cells in multiple human organs", Cell Stem Cell, 3, pp.301~313 (2008)
  11. Deans RJ, "Mesenchymal stem cells:biology and potential clinical uses", Exp Hematol, 28, pp.875~884 (2000)
  12. Digirolamo CM, "Propagation and senescence of human marrow stromal cells in culture: A simple colonyforming assay identifies samples with the greatest potential to propagate and differentiate", Br J Haematol, 107, pp.275~281 (1999)
  13. Duscher D, "Aging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells", Sci Rep, 4, pp.7144~ (2014)
  14. Evans MJ, "Establishment in culture of pluripotential cells from mouse embryos", Nature, 292, pp.154~156 (1981)
  15. Fahrer C, "Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan", Aging Cell, 6, pp.745~757 (2007)
  16. Faiella W, "Therapeutic use of stem cells for cardiovascular disease", Clin Transl Med, 5, pp.34~ (2016)
  17. Gharibi B, "Effects of medium supplements on proliferation, differentiation potential, and in vitro expansion of mesenchymal stem cells", Stem Cells Transl Med, 1, pp.771~782 (2012)
  18. Gu Z, "Rapamycin reverses the senescent phenotype and improves immunoregulation of mesenchymal stem cells from MRL", lpr mice and systemic lupus erythematosus patients through inhibition of the mTOR signaling pathway, 2016, pp.8, 1102~1114
  19. Hsuan YC, "Mesenchymal stem cell-based treatments for stroke, neural trauma, and heatstroke", Brain Behav, 6, pp.e00526~ (2016)
  20. In 't Anker PS, "Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta", Stem Cells, 22, pp.1338~1345 (2004)
  21. In 't Anker PS, "Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation", Blood, 102, pp.1548~1549 (2003)
  22. Jin Y, "Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16and extracellular signal regulated kinase", Biochem Biophys Res Commun, 391, pp.1471~1476 (2010)
  23. Jung EM, "Evidences for correlation between the reduced VCAM-1 expression and hyaluronan synthesis during cellular senescence of human mesenchymal stem cells", Biochem Biophys Res Commun, 404, pp.463~469 (2011)
  24. Jung JW, "Histone deacetylase controls adult stem cell aging by balancing the expression of polycomb genes and jumonji domain containing 3", Cell Mol Life Sci, 67, pp.1165~1176 (2010)
  25. Kashino G, "Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Werner syndrome fibroblast cells", Free Radic Biol Med, 35, pp.438~443 (2003)
  26. Kim M, "Agerelated alterations in mesenchymal stem cells related to shift in differentiation from osteogenic to adipogenic potential: Implication to age-associated bone diseases and defects", Mech Ageing Dev, 133, pp.215~225 (2012)
  27. Ko E, "Human umbilical cord blood-derived mesenchymal stem cells undergo cellular senescence in response to oxidative stress", Stem Cells Dev, 21, pp.1877~1886 (2012)
  28. Kretlow JD, "Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells", BMC Cell Biol, 9, pp.60~ (2008)
  29. Laurent LC, "Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture", Cell Stem Cell, 8, pp.106~118 (2011)
  30. LeBlanc KT, "HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells", Exp Hematol, 31, pp.890~896 (2003)
  31. Lee H, "Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons", Stem Cells, 25, pp.1931~1939 (2007)
  32. Liang G, "Genetic and epigenetic variations in iPSCs: potential causes and implications for application", Cell Stem Cell, 13, pp.149~159 (2013)
  33. Limn TM, "Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants", Stem Cells Dev, 14, pp.92~102 (2005)
  34. Liu D, "Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion", Cancer Res, 67, pp.3117~3126 (2007)
  35. Liu Y, "Recent Progress in Stem Cell Therapy for Diabetic Nephropathy", Kidney Dis, 2, pp.20~27 (2016)
  36. Martins-Taylor K, "Recurrent copy number variations in human induced pluripotent stem cel", Nat Biotechnol, 29, pp.488~491 (2011)
  37. Mayshar Y, "Identification and classification of chromosomal aberrations in human induced pluripotent stem cells", Cell Stem Cell, 7, pp.521~531 (2010)
  38. Minieri V, "Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells", J Cell Mol Med, 19, pp.734~743 (2015)
  39. Monsel A, "Preclinical evidence and ongoing clinical trials using mesenchymal stem cells", Anesthesiology, 121, pp.1099~1121 (2015)
  40. Muthna D, "Irradiation of adult human dental pulp stem cells provokes activation of p53, cell cycle arrest, and senescence but not apoptosis", Stem Cells Dev, 19, pp.1855~1862 (2010)
  41. Nazor KL, "Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives", Cell Stem Cell, 10, pp.620~634 (2012)
  42. Park IH, "Reprogramming of human somatic cells to pluripotency with defined factors", Nature, 451, pp.141~146 (2008)
  43. Park JS, "Increased caveolin-1, a cause for the declined adipogenic potential of senescent human mesenchymal stem cells", Mech Ageing Dev, 126, pp.551~559 (2005)
  44. Pati S, "Neurogenic plasticity of mesenchymal stem cell, an alluring cellular replacement for traumatic brain injury", Curr Stem Cell Res Ther, 11, pp.149~157 (2016)
  45. Pittenger MF, "Multilineage potential of adult human mesenchymal stem cells", Science, 284, pp.143~147 (1999)
  46. Pittenger MF, "Mesenchymal stem cells and their potential as cardiac therapeutics", Cir Res, 95, pp.9~20 (2004)
  47. Romanov YA, "Searching for alternative sources of post-natal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord", Stem Cells, 21, pp.105~110 (2003)
  48. Sepulveda JC, "Cell Senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model", Stem Cells, 32, pp.1865~1877 (2014)
  49. Takahashi K, "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors", Cell, 126, pp.663~676 (2006)
  50. Tang H, "Dual expression of hTERT and VEGF prolongs life span and enhances angiogenic ability of aged BMSCs", Biochem Biophys Res Commun, 440, pp.502~508 (2013)
  51. Thomson JA, "Embryonic stem cell lines derived from human blastocysts", Science, 282, pp.1145~1147 (1998)
  52. Tian S, "Heart regeneration with embryonic cardiac progenitor cells and cardiac tissue engineering", J Stem Cell Transplant Biol, 1, pp.104~129 (2015)
  53. Turinetto V, "Senescence in human mesenchymal stem cells: Functional changes and implications in stem cell-based therapy", Int J Mol Sci, 17, pp.E1164~ (2016)
  54. Wagner W, "Replicative senescence of mesenchymal stem cells: a continuous and organized process", PLoS One, 3, pp.e2213~ (2008)
  55. Wang SS, "Aging as an essential modifier for the efficacy in mesenchymal stem cell therapy through an inositol phosphate 6 kinase-inositolo pyrophosphate 7-dependent mechanism", Stem Cell Res, 5, pp.43~ (2014)
  56. Wang Y, "Safety of mesenchymal stem cells for clinical application", Stem Cells Int, 2012, pp.652034~ (2012)
  57. Wutz A, "Epigenetic alterations in human pluripotent stem cells: a tale of two cultures", Cell Stem Cell, 11, pp.9~15 (2012)
  58. Xia Y, "Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells", Nat Cell Biol, 15, pp.1507~1515 (2013)
  59. Young MA, "Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells", Cell Stem Cell, 10, pp.570~582 (2012)
  60. Zhang J, "LIN28 Regulates stem cell metabolism and conversion to primed pluripotency", Cell Stem Cell, 19, pp.66~80 (2016)
  61. Zuk PA, "Human adipose tissue is a source of multipotent stem cells", Mol Biol Cell, 13, pp.4279~4295 (2002)

관련 논문AI추천

Mesenchymal Stem Cell-derived Exosomes: Applications in Cell-free Therapy김진관, 허준석대한임상검사과학회 · 대한임상검사과학회지2018 · 제50권 제4호임상적용을 위한 세포치료제로서의 성체 중간엽줄기세포송인환영남대학교 의과대학 · Journal of Yeungnam Medical Science2009 · 제26권 제1호Mesenchymal Stem Cells for the Treatment of Liver Disease: Present and Perspectives엄영우, Moon Young Kim, Seong Hee Kang, Soon Koo Baik거트앤리버 소화기연관학회협의회 · Gut and Liver2020 · 제14권 제3호The potential of mesenchymal stem cells derived from amniotic membrane and amniotic fluid for neuronal regenerative therapy김민규, 김은영, 이경본생화학분자생물학회 · BMB Reports2014 · 제47권 제3호Neurorestoration Induced by Mesenchymal Stem Cells: Potential Therapeutic Mechanisms for Clinical Trials서정화, 조성래연세대학교의과대학 · Yonsei Medical Journal2012 · 제53권 제6호Impact of mesenchymal stem cell senescence on inflammaging유경록, Byung-Chul Lee생화학분자생물학회 · BMB Reports2020 · 제53권 제2호

이 간행물의 다른 논문 (10건)

Expression of Ion Channels in Perivascular Stem Cells derived from Human Umbilical Cords홍석호, 박원선, 김은비pp. 11-18Effects of Clove Oil and Lidocaine-HCl Anesthesia on Water Parameter during Simulated Transportation in the Marine Medaka, Oryzias dancena김동수, 임상구, 길현우, 박인석, 이태호, 남윤권pp. 19-33Serum Cytokine Levels are related to Nesfatin-1/NUCB2 Expression in the Implantation Sites of Spontaneous Abortion Model of CBA/j × DBA/2 Mice선소정, 김희정, Yiwa Chung, 양현원pp. 35-46Effects of Cell Cycle Regulators on the Cell Cycle Synchronization of Porcine induced Pluripotent Stem Cells옥선아, 황성수, 양현, 박미령, 곽태욱, 오건봉, 우재석, 황인설, 권대진, 임기선pp. 47-54Morphometric Characteristic between Diploid and Spontaneous Triploid Carp in Korea한형건, 임상구, 길현우, 구인본, 박인석, 이태호pp. 55-62
원문 보기