Cellular and Molecular Life Sciences

, Volume 74, Issue 14, pp 2587–2600 | Cite as

Effect of hypoxia on human adipose-derived mesenchymal stem cells and its potential clinical applications

  • Jane Ru ChoiEmail author
  • Kar Wey Yong
  • Wan Kamarul Zaman Wan SafwaniEmail author


Human adipose-derived mesenchymal stem cells (hASCs) are an ideal cell source for regenerative medicine due to their capabilities of multipotency and the readily accessibility of adipose tissue. They have been found residing in a relatively low oxygen tension microenvironment in the body, but the physiological condition has been overlooked in most studies. In light of the escalating need for culturing hASCs under their physiological condition, this review summarizes the most recent advances in the hypoxia effect on hASCs. We first highlight the advantages of using hASCs in regenerative medicine and discuss the influence of hypoxia on the phenotype and functionality of hASCs in terms of viability, stemness, proliferation, differentiation, soluble factor secretion, and biosafety. We provide a glimpse of the possible cellular mechanism that involved under hypoxia and discuss the potential clinical applications. We then highlight the existing challenges and discuss the future perspective on the use of hypoxic-treated hASCs.


Hypoxia hASCs Phenotype Functionality Clinical applications Challenges 



The work was supported by the UM High Impact Research Grant UM-MOHE (UM.C/HIR/MOHE/ENG/44) from the Ministry of Higher Education Malaysia and the University of Malaya Research Grant (UMRG: RP040B-15HTM).


  1. 1.
    Harandi OF, Ambros VR (2015) Control of stem cell self-renewal and differentiation by the heterochronic genes and the cellular asymmetry machinery in Caenorhabditis elegans. Proc Natl Acad Sci 112(3):E287–E296CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Weissman IL (2015) Stem cells are units of natural selection for tissue formation, for germline development, and in cancer development. Proc Natl Acad Sci 112(29):8922–8928CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Frenette PS, Pinho S, Lucas D, Scheiermann C (2013) Mesenchymal stem cell: keystone of the hematopoietic stem cell niche and a stepping-stone for regenerative medicine. Annu Rev Immunol 31:285–316CrossRefPubMedGoogle Scholar
  4. 4.
    Ankrum JA, Ong JF, Karp JM (2014) Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol 32(3):252–260CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yong KW, Wan Safwani WK, Xu F, Wan Abas WA, Choi JR, Pingguan-Murphy B (2015) Cryopreservation of human mesenchymal stem cells for clinical applications: current methods and challenges. Biopreserv Biobank 13(4):231–239CrossRefPubMedGoogle Scholar
  6. 6.
    Duscher D, Luan A, Rennert RC, Atashroo D, Maan ZN, Brett EA, Whittam AJ, Ho N, Lin M, Hu MS (2016) Suction assisted liposuction does not impair the regenerative potential of adipose derived stem cells. J Transl Med 14(1):1CrossRefGoogle Scholar
  7. 7.
    Duscher D, Atashroo D, Maan ZN, Luan A, Brett EA, Barrera J, Khong SM, Zielins ER, Whittam AJ, Hu MS (2016) Ultrasound-assisted liposuction does not compromise the regenerative potential of adipose-derived stem cells. Stem Cells Transl Med 5(2):248–257CrossRefPubMedGoogle Scholar
  8. 8.
    Choi JR, Pingguan-Murphy B, Abas WABW, Yong KW, Poon CT, Azmi MAN, Omar SZ, Chua KH, Xu F, Safwani WKZW (2015) In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis. PLoS One 10(1):e0115034CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Yong KW, Safwani WKZW, Xu F, Zhang X, Choi JR, Abas WABW, Omar SZ, Azmi MAN, Chua KH, Pingguan-Murphy B (2016) Assessment of tumourigenic potential in long-term cryopreserved human adipose-derived stem cells. J Tissue Eng Regen Med. doi: 10.1002/term.2120
  10. 10.
    Pérez LM, Bernal A, San Martín N, Lorenzo M, Fernández-Veledo S, Gálvez BG (2013) Metabolic rescue of obese adipose-derived stem cells by Lin28/Let7 pathway. Diabetes 62(7):2368–2379CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Eljaafari A, Robert M, Chehimi M, Chanon S, Durand C, Vial G, Bendridi N, Madec A-M, Disse E, Laville M (2015) Adipose tissue-derived stem cells from obese subjects contribute to inflammation and reduced insulin response in adipocytes through differential regulation of the Th1/Th17 balance and monocyte activation. Diabetes 64(7):2477–2488CrossRefPubMedGoogle Scholar
  12. 12.
    Choi JR, Pingguan-Murphy B, Wan Abas WA, Noor Azmi MA, Omar SZ, Chua KH, Wan Safwani WK (2014) Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells. Biochem Biophys Res Commun 448(2):218–224CrossRefPubMedGoogle Scholar
  13. 13.
    Skiles ML, Sahai S, Rucker L, Blanchette JO (2013) Use of culture geometry to control hypoxia-induced vascular endothelial growth factor secretion from adipose-derived stem cells: optimizing a cell-based approach to drive vascular growth. Tissue Eng Part A 19(21–22):2330–2338CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Portron S, Merceron C, Gauthier O, Lesoeur J, Sourice S, Masson M, Fellah BH, Geffroy O, Lallemand E, Weiss P, Guicheux J, Vinatier C (2013) Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair. PLoS One 8:4CrossRefGoogle Scholar
  15. 15.
    Choi JR, Pingguan-Murphy B, Abas WABW, Azmi MAN, Omar SZ, Chua KH, Safwani WKZW (2014) Hypoxia promotes growth and viability of human adipose-derived stem cells with increased growth factors secretion. J Asian Sci Res 4(7):328–338Google Scholar
  16. 16.
    Safwani WKZW, Wong CW, Yong KW, Choi JR, Adenan NAM, Omar SZ, Abas WABW, Pingguan-Murphy B (2016) The effects of hypoxia and serum-free conditions on the stemness properties of human adipose-derived stem cells. Cytotechnology:1–14Google Scholar
  17. 17.
    Kim JH, Kim SH, Song SY, Kim WS, Song SU, Yi T, Jeon MS, Chung HM, Xia Y, Sung JH (2014) Hypoxia induces adipocyte differentiation of adipose-derived stem cells by triggering reactive oxygen species generation. Cell Biol Int 38(1):32–40CrossRefPubMedGoogle Scholar
  18. 18.
    Fotia C, Massa A, Boriani F, Baldini N, Granchi D (2015) Hypoxia enhances proliferation and stemness of human adipose-derived mesenchymal stem cells. CytoTechnology 67(6):1073–1084CrossRefPubMedGoogle Scholar
  19. 19.
    Das R, Jahr H, van Osch GJ, Farrell E (2009) The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng Part B Rev 16(2):159–168CrossRefGoogle Scholar
  20. 20.
    Haque N, Rahman MT, Abu Kasim NH, Alabsi AM (2013) Hypoxic culture conditions as a solution for mesenchymal stem cell based regenerative therapy. Sci World J. doi: 10.1155/2013/632972
  21. 21.
    Buravkova L, Andreeva E, Gogvadze V, Zhivotovsky B (2014) Mesenchymal stem cells and hypoxia: where are we? Mitochondrion 19:105–112CrossRefPubMedGoogle Scholar
  22. 22.
    Ejtehadifar M, Shamsasenjan K, Movassaghpour A, Akbarzadehlaleh P, Dehdilani N, Abbasi P, Molaeipour Z, Saleh M (2015) The effect of hypoxia on mesenchymal stem cell biology. Adv Pharm Bull 5(2):141CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Buravkova L, Andreeva E, Grigoriev A (2012) The impact of oxygen in physiological regulation of human multipotent mesenchymal cell functions. Hum Physiol 38(4):444–452CrossRefGoogle Scholar
  24. 24.
    Krähenbühl S, Grognuz A, Michetti M, Raffoul W, Applegate L (2015) Enhancement of human adipose-derived stem cell expansion and stability for clinical use. Int J Stem Cell Res Ther 2:007Google Scholar
  25. 25.
    Walmsley GG, Atashroo DA, Maan ZN, Hu MS, Zielins ER, Tsai JM, Duscher D, Paik K, Tevlin R, Marecic O (2015) High-throughput screening of surface marker expression on undifferentiated and differentiated human adipose-derived stromal cells. Tissue Eng Part A 21(15–16):2281–2291CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Rodbell M (1966) Metabolism of isolated fat cells II. The similar effects of phospholipase C (Clostridium perfringens α toxin) and of insulin on glucose and amino acid metabolism. J Biol Chem 241(1):130–139PubMedGoogle Scholar
  27. 27.
    Aronowitz JA, Lockhart RA, Hakakian CS, Hicok KC (2015) Clinical safety of stromal vascular fraction separation at the point of care. Ann Plast Surg 75(6):666–671CrossRefPubMedGoogle Scholar
  28. 28.
    Mizuno H, Tobita M, Uysal AC (2012) Concise review: adipose-derived stem cells as a novel tool for future regenerative medicine. Stem Cells 30(5):804–810CrossRefPubMedGoogle Scholar
  29. 29.
    Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH (2005) Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 54(3):132–141CrossRefPubMedGoogle Scholar
  30. 30.
    Hu HH, Yin L, Aggabao PC, Perkins TG, Chia JM, Gilsanz V (2013) Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI. J Magn Reson Imaging 38(4):885–896CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Tsuji W, Rubin JP, Marra KG (2014) Adipose-derived stem cells: implications in tissue regeneration. World. J Stem Cells 6(3):312–321CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Silva FJ, Holt DJ, Vargas V, Yockman J, Boudina S, Atkinson D, Grainger DW, Revelo MP, Sherman W, Bull DA (2014) Metabolically active human brown adipose tissue derived stem cells. Stem Cells 32(2):572–581CrossRefPubMedGoogle Scholar
  33. 33.
    Silva AC, Percegona LS, Franca AL, Dos Santos TM, Perini CC, Gonzalez P, Rebelatto CL, Camara NO, Aita CA (2012) Expression of pancreatic endocrine markers by mesenchymal stem cells from human adipose tissue. Transplant Proc 44(8):2495–2496CrossRefPubMedGoogle Scholar
  34. 34.
    Dzobo K, Turnley T, Wishart A, Rowe A, Kallmeyer K, van Vollenstee FA, Thomford NE, Dandara C, Chopera D, Pepper MS (2016) Fibroblast-derived extracellular matrix induces chondrogenic differentiation in human adipose-derived mesenchymal stromal/stem cells in vitro. Int J Mol Sci 17(8):1259CrossRefPubMedCentralGoogle Scholar
  35. 35.
    Lee J, Han D-J, Kim S-C (2008) In vitro differentiation of human adipose tissue-derived stem cells into cells with pancreatic phenotype by regenerating pancreas extract. Biochem Biophys Res Commun 375(4):547–551. doi: 10.1016/j.bbrc.2008.08.064 CrossRefPubMedGoogle Scholar
  36. 36.
    Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived stem cells for regenerative medicine. Circ Res 100(9):1249–1260CrossRefPubMedGoogle Scholar
  37. 37.
    Liu L, Gao J, Yuan Y, Chang Q, Liao Y, Lu F (2013) Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF. Cell Biol Int 37(6):551–560CrossRefPubMedGoogle Scholar
  38. 38.
    Yong KW, Li Y, Liu F, Gao B, Lu TJ, Abas WABW, Safwani WKZW, Pingguan-Murphy B, Ma Y, Xu F (2016) Paracrine effects of adipose-derived stem cells on matrix stiffness-induced cardiac myofibroblast differentiation via angiotensin II type 1 receptor and Smad7. Sci Rep. doi: 10.1038/srep33067
  39. 39.
    Feng Y, Zhu M, Dangelmajer S, Lee YM, Wijesekera O, Castellanos CX, Denduluri A, Chaichana KL, Li Q, Zhang H, Levchenko A, Guerrero-Cazares H, Quinones-Hinojosa A (2014) Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer. Cell Death Dis 11(5):521Google Scholar
  40. 40.
    Stubbs SL, Hsiao ST, Peshavariya HM, Lim SY, Dusting GJ, Dilley RJ (2012) Hypoxic preconditioning enhances survival of human adipose-derived stem cells and conditions endothelial cells in vitro. Stem Cells Dev 21(11):1887–1896CrossRefPubMedGoogle Scholar
  41. 41.
    Valorani MG, Montelatici E, Germani A, Biddle A, D’Alessandro D, Strollo R, Patrizi MP, Lazzari L, Nye E, Otto WR, Pozzilli P, Alison MR (2012) Pre-culturing human adipose tissue mesenchymal stem cells under hypoxia increases their adipogenic and osteogenic differentiation potentials. Cell Prolif 45(3):225–238CrossRefPubMedGoogle Scholar
  42. 42.
    Merceron C, Vinatier C, Portron S, Masson M, Amiaud J, Guigand L, Cherel Y, Weiss P, Guicheux J (2010) Differential effects of hypoxia on osteochondrogenic potential of human adipose-derived stem cells. Am J Physiol Cell Physiol 298(2):25CrossRefGoogle Scholar
  43. 43.
    Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL (2004) Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109(10):1292–1298CrossRefPubMedGoogle Scholar
  44. 44.
    Khan WS, Adesida AB, Hardingham TE (2007) Hypoxic conditions increase hypoxia-inducible transcription factor 2alpha and enhance chondrogenesis in stem cells from the infrapatellar fat pad of osteoarthritis patients. Arthritis Res Ther 9(3)Google Scholar
  45. 45.
    Wan Safwani WK, Makpol S, Sathapan S, Chua KH (2011) The changes of stemness biomarkers expression in human adipose-derived stem cells during long-term manipulation. Biotechnol Appl Biochem 58(4):261–270CrossRefPubMedGoogle Scholar
  46. 46.
    Yong KW, Pingguan-Murphy B, Xu F, Abas WA, Choi JR, Omar SZ, Azmi MA, Chua KH, Wan Safwani WK (2015) Phenotypic and functional characterization of long-term cryopreserved human adipose-derived stem cells. Sci Rep 5:9596CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. CytoTherapy 8(4):315–317CrossRefPubMedGoogle Scholar
  48. 48.
    Roemeling-van Rhijn M, Mensah FK, Korevaar SS, Leijs MJ, van Osch GJ, Ijzermans JN, Betjes MG, Baan CC, Weimar W, Hoogduijn MJ (2013) Effects of hypoxia on the immunomodulatory properties of adipose tissue-derived mesenchymal stem cells. Front Immunol 4:203CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Schiller ZA, Schiele NR, Sims JK, Lee K, Kuo CK (2013) Adipogenesis of adipose-derived stem cells may be regulated via the cytoskeleton at physiological oxygen levels in vitro. Stem Cell Res Ther 4:4CrossRefGoogle Scholar
  50. 50.
    Munir S, Foldager CB, Lind M, Zachar V, Soballe K, Koch TG (2014) Hypoxia enhances chondrogenic differentiation of human adipose tissue-derived stromal cells in scaffold-free and scaffold systems. Cell Tissue Res 355(1):89–102CrossRefPubMedGoogle Scholar
  51. 51.
    Wang DW, Fermor B, Gimble JM, Awad HA, Guilak F (2005) Influence of oxygen on the proliferation and metabolism of adipose derived adult stem cells. J Cell Physiol 204(1):184–191CrossRefPubMedGoogle Scholar
  52. 52.
    Wan Safwani WKZ, Choi JR, Yong KW, Ting I, Adenan NAM, Pingguan-Murphy B (2017) Hypoxia enhances the viability, growth and chondrogenic potential of cryopreserved human adipose-derived stem cells. Cryobiology. doi: 10.1016/j.cryobiol.2017.01.006
  53. 53.
    Wan Safwani WK, Wong CW, Yong KW, Choi JR, Mat Adenan NA, Omar SZ, Wan Abas WA, Pingguan-Murphy B (2016) The effects of hypoxia and serum-free conditions on the stemness properties of human adipose-derived stem cells. CytoTechnology 4:4Google Scholar
  54. 54.
    Bekhite MM, Finkensieper A, Rebhan J, Huse S, Schultze-Mosgau S, Figulla HR, Sauer H, Wartenberg M (2014) Hypoxia, leptin, and vascular endothelial growth factor stimulate vascular endothelial cell differentiation of human adipose tissue-derived stem cells. Stem Cells Dev 23(4):333–351CrossRefPubMedGoogle Scholar
  55. 55.
    Hsiao ST, Lokmic Z, Peshavariya H, Abberton KM, Dusting GJ, Lim SY, Dilley RJ (2013) Hypoxic conditioning enhances the angiogenic paracrine activity of human adipose-derived stem cells. Stem Cells Dev 22(10):1614–1623CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Linero I, Chaparro O (2014) Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One 9:9CrossRefGoogle Scholar
  57. 57.
    Przybyt E, Krenning G, Brinker MG, Harmsen MC (2013) Adipose stromal cells primed with hypoxia and inflammation enhance cardiomyocyte proliferation rate in vitro through STAT3 and Erk1/2. J Transl Med 11(39):1479–5876Google Scholar
  58. 58.
    Estrada JC, Albo C, Benguria A, Dopazo A, Lopez-Romero P, Carrera-Quintanar L, Roche E, Clemente EP, Enriquez JA, Bernad A, Samper E (2012) Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis. Cell Death Differ 19(5):743–755CrossRefPubMedGoogle Scholar
  59. 59.
    Semenza GL (2014) Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu Rev Pathol Mech Dis 9:47–71CrossRefGoogle Scholar
  60. 60.
    Borsi E, Terragna C, Brioli A, Tacchetti P, Martello M, Cavo M (2015) Therapeutic targeting of hypoxia and hypoxia-inducible factor 1 alpha in multiple myeloma. Transl Res 165(6):641–650CrossRefPubMedGoogle Scholar
  61. 61.
    Palomäki S, Pietilä M, Laitinen S, Pesälä J, Sormunen R, Lehenkari P, Koivunen P (2013) HIF-1α is upregulated in human mesenchymal stem cells. Stem Cells 31(9):1902–1909CrossRefPubMedGoogle Scholar
  62. 62.
    Lord-Dufour S, Copland IB, Levros LC, Post M, Das A, Khosla C, Galipeau J, Rassart E, Annabi B (2009) Evidence for transcriptional regulation of the glucose-6-phosphate transporter by HIF-1α: targeting G6PT with Mumbaistatin analogs in hypoxic mesenchymal stromal cells. Stem Cells 27(3):489–497CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Grayson WL, Zhao F, Izadpanah R, Bunnell B, Ma T (2006) Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs. J Cell Physiol 207(2):331–339CrossRefPubMedGoogle Scholar
  64. 64.
    Hu X, Yu SP, Fraser JL, Lu Z, Ogle ME, Wang J-A, Wei L (2008) Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thorac Cardiovasc Surg 135(4):799–808CrossRefPubMedGoogle Scholar
  65. 65.
    Hung SC, Pochampally RR, Chen SC, Hsu SC, Prockop DJ (2007) Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells 25(9):2363–2370CrossRefPubMedGoogle Scholar
  66. 66.
    Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K-i, Shimada T, Oike Y, Imaizumi T (2001) Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103(23):2776–2779CrossRefPubMedGoogle Scholar
  67. 67.
    Rodrigues M, Griffith LG, Wells A (2010) Growth factor regulation of proliferation and survival of multipotential stromal cells. Stem Cell Res Ther 1(4):1CrossRefGoogle Scholar
  68. 68.
    Robins JC, Akeno N, Mukherjee A, Dalal RR, Aronow BJ, Koopman P, Clemens TL (2005) Hypoxia induces chondrocyte-specific gene expression in mesenchymal cells in association with transcriptional activation of Sox9. Bone 37(3):313–322CrossRefPubMedGoogle Scholar
  69. 69.
    Duval E, Baugé C, Andriamanalijaona R, Bénateau H, Leclercq S, Dutoit S, Poulain L, Galéra P, Boumédiene K (2012) Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering. Biomaterials 33(26):6042–6051CrossRefPubMedGoogle Scholar
  70. 70.
    Shang J, Liu H, Li J, Zhou Y (2014) Roles of hypoxia during the chondrogenic differentiation of mesenchymal stem cells. Curr Stem Cell Res Ther 9(2):141–147CrossRefPubMedGoogle Scholar
  71. 71.
    Fehrer C, Brunauer R, Laschober G, Unterluggauer H, Reitinger S, Kloss F, Gully C, Gassner R, Lepperdinger G (2007) Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan. Aging Cell 6(6):745–757CrossRefPubMedGoogle Scholar
  72. 72.
    Xu N, Liu H, Qu F, Fan J, Mao K, Yin Y, Liu J, Geng Z, Wang Y (2013) Hypoxia inhibits the differentiation of mesenchymal stem cells into osteoblasts by activation of Notch signaling. Exp Mol Pathol 94(1):33–39CrossRefPubMedGoogle Scholar
  73. 73.
    Lin Q, Lee Y-J, Yun Z (2006) Differentiation arrest by hypoxia. J Biol Chem 281(41):30678–30683CrossRefPubMedGoogle Scholar
  74. 74.
    Liu H, Liu S, Li Y, Wang X, Xue W, Ge G, Luo X (2012) The role of SDF-1-CXCR4/CXCR7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury. PLoS One 7(4):e34608CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Shi M, Li J, Liao L, Chen B, Li B, Chen L, Jia H, Zhao RC (2007) Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica 92(7):897–904CrossRefPubMedGoogle Scholar
  76. 76.
    Leroux L, Descamps B, Tojais NF, Séguy B, Oses P, Moreau C, Daret D, Ivanovic Z, Boiron J-M, Lamazière J-MD (2010) Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4-dependent pathway. Mol Ther 18(8):1545–1552CrossRefPubMedCentralGoogle Scholar
  77. 77.
    Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisen J (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Kajstura J, Rota M, Cappetta D, Ogorek B, Arranto C, Bai Y, Ferreira-Martins J, Signore S, Sanada F, Matsuda A, Kostyla J, Caballero MV, Fiorini C, D’Alessandro DA, Michler RE, del Monte F, Hosoda T, Perrella MA, Leri A, Buchholz BA, Loscalzo J, Anversa P (2012) Cardiomyogenesis in the aging and failing human heart. Circulation 126(15):1869–1881CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Hwang H, Kloner RA (2010) Improving regenerating potential of the heart after myocardial infarction: factor-based approach. Life Sci 86(13–14):461–472CrossRefPubMedGoogle Scholar
  80. 80.
    Willems E, Lanier M, Forte E, Lo F, Cashman J, Mercola M (2011) A chemical biology approach to myocardial regeneration. J Cardiovasc Transl Res 4(3):340–350CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    J Salgado A, L Reis R, Sousa N, M Gimble J (2010) Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther 5(2):103–110CrossRefGoogle Scholar
  82. 82.
    Matsushita K, Iwanaga S, Oda T, Kimura K, Shimada M, Sano M, Umezawa A, Hata J, Ogawa S (2005) Interleukin-6/soluble interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis. Lab Invest 85(10):1210–1223CrossRefPubMedGoogle Scholar
  83. 83.
    Buckwalter JA, Mankin HJ (1998) Articular cartilage repair and transplantation. Arthritis Rheum 41(8):1331–1342CrossRefPubMedGoogle Scholar
  84. 84.
    Marquass B, Schulz R, Hepp P, Zscharnack M, Aigner T, Schmidt S, Stein F, Richter R, Osterhoff G, Aust G, Josten C, Bader A (2011) Matrix-associated implantation of predifferentiated mesenchymal stem cells versus articular chondrocytes: in vivo results of cartilage repair after 1 year. Am J Sports Med 39(7):1401–1412CrossRefPubMedGoogle Scholar
  85. 85.
    Zscharnack M, Hepp P, Richter R, Aigner T, Schulz R, Somerson J, Josten C, Bader A, Marquass B (2010) Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model. Am J Sports Med 38(9):1857–1869CrossRefPubMedGoogle Scholar
  86. 86.
    Yong KW, Choi JR, Safwani WKZW (2016) Biobanking of human mesenchymal stem cells: future strategy to facilitate clinical applications. In: Biobanking and cryopreservation of stem cells. Springer, pp 99–110Google Scholar
  87. 87.
    Otto WR, Wright NA (2011) Mesenchymal stem cells: from experiment to clinic. Fibrogenesis Tissue Repair 4(20):1755–1536Google Scholar
  88. 88.
    Wang S, Qu X, Zhao RC (2012) Clinical applications of mesenchymal stem cells. J Hematol Oncol 5(19):1756–8722Google Scholar

Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  1. 1.Department of Biomedical Engineering, Faculty of EngineeringUniversity of MalayaKuala LumpurMalaysia

Personalised recommendations