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Cellular and Molecular Life Sciences

, Volume 73, Issue 17, pp 3311–3321 | Cite as

Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential

Review

Abstract

Mesenchymal stem cells (MSC) are capable of differentiating into cells of multiple cell lineages and have potent paracrine effects. Due to their easy preparation and low immunogenicity, MSC have emerged as an extremely promising therapeutic agent in regenerative medicine for diverse diseases. However, MSC are heterogeneous with respect to phenotype and function in current isolation and cultivation regimes, which often lead to incomparable experimental results. In addition, there may be specific stem cell subpopulations with definite differentiation capacity toward certain lineages in addition to stem cells with multi-differentiation potential. Recent studies have identified several subsets of MSC which exhibit distinct features and biological activities, and enhanced therapeutic potentials for certain diseases. In this review, we give an overview of these subsets for their phenotypic, biological and functional properties.

Keywords

Stromal cells Heterogeneity Cell surface markers PDGFR CD146 

Notes

Acknowledgments

This work was supported by grants from Natural Science Foundation of China (No. 31371404, 31571429), Natural Science Foundation of Guangdong (2015A030311041), and Shenzhen Science and Technology Innovation Committee (JCYJ20140417115840279, GJHZ20150316160614842).

References

  1. 1.
    Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3(4):393–403PubMedGoogle Scholar
  2. 2.
    Dmitrieva RI, Minullina IR, Bilibina AA et al (2012) Bone marrow- and subcutaneous adipose tissue-derived mesenchymal stem cells: differences and similarities. Cell Cycle 11(2):377–383. doi: 10.4161/cc.11.2.18858 PubMedCrossRefGoogle Scholar
  3. 3.
    Soncini M, Vertua E, Gibelli L et al (2007) Isolation and characterization of mesenchymal cells from human fetal membranes. J Tissue Eng Regen Med 1(4):296–305. doi: 10.1002/term.40 PubMedCrossRefGoogle Scholar
  4. 4.
    Yang ZX, Han ZB, Ji YR et al (2013) CD106 identifies a subpopulation of mesenchymal stem cells with unique immunomodulatory properties. PLoS One 8(3):e59354. doi: 10.1371/journal.pone.0059354 PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Xu J, Liao W, Gu D et al (2009) Neural ganglioside GD2 identifies a subpopulation of mesenchymal stem cells in umbilical cord. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 23(4–6):415–424. doi: 10.1159/000218188 CrossRefGoogle Scholar
  6. 6.
    Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147PubMedCrossRefGoogle Scholar
  7. 7.
    Phinney DG, Prockop DJ (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair–current views. Stem Cells 25(11):2896–2902. doi: 10.1634/stemcells.2007-0637 PubMedCrossRefGoogle Scholar
  8. 8.
    Liechty KW, MacKenzie TC, Shaaban AF et al (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6(11):1282–1286. doi: 10.1038/81395 PubMedCrossRefGoogle Scholar
  9. 9.
    Lin RZ, Moreno-Luna R, Li D et al (2014) Human endothelial colony-forming cells serve as trophic mediators for mesenchymal stem cell engraftment via paracrine signaling. Proc Natl Acad Sci USA 111(28):10137–10142. doi: 10.1073/pnas.1405388111 PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Wu Y, Chen L, Scott PG et al (2007) Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 25(10):2648–2659. doi: 10.1634/stemcells.2007-0226 PubMedCrossRefGoogle Scholar
  11. 11.
    Wu Y, Zhao RC, Tredget EE (2010) Concise review: bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration. Stem Cells 28(5):905–915. doi: 10.1002/stem.420 PubMedPubMedCentralGoogle Scholar
  12. 12.
    Chamberlain J, Yamagami T, Colletti E et al (2007) Efficient generation of human hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep. Hepatology 46(6):1935–1945. doi: 10.1002/hep.21899 PubMedCrossRefGoogle Scholar
  13. 13.
    Tamai K, Yamazaki T, Chino T et al (2011) PDGFRalpha-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia. Proc Natl Acad Sci USA 108(16):6609–6614. doi: 10.1073/pnas.1016753108 PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Parekkadan B, Milwid JM (2010) Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng 12:87–117. doi: 10.1146/annurev-bioeng-070909-105309 PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kim YS, Park EH, Kim YC et al (2013) Clinical outcomes of mesenchymal stem cell injection with arthroscopic treatment in older patients with osteochondral lesions of the talus. Am J Sports Med 41(5):1090–1099. doi: 10.1177/0363546513479018 PubMedCrossRefGoogle Scholar
  16. 16.
    Trounson A, McDonald C (2015) Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17(1):11–22. doi: 10.1016/j.stem.2015.06.007 PubMedCrossRefGoogle Scholar
  17. 17.
    Lv FJ, Tuan RS, Cheung KM et al (2014) Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells 32(6):1408–1419. doi: 10.1002/stem.1681 PubMedCrossRefGoogle Scholar
  18. 18.
    Rostovskaya M, Anastassiadis K (2012) Differential expression of surface markers in mouse bone marrow mesenchymal stromal cell subpopulations with distinct lineage commitment. PLoS One 7(12):e51221. doi: 10.1371/journal.pone.0051221 PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317. doi: 10.1080/14653240600855905 PubMedCrossRefGoogle Scholar
  20. 20.
    Phinney DG (2012) Functional heterogeneity of mesenchymal stem cells: implications for cell therapy. J Cell Biochem 113(9):2806–2812. doi: 10.1002/jcb.24166 PubMedCrossRefGoogle Scholar
  21. 21.
    Tormin A, Brune JC, Olsson E et al (2009) Characterization of bone marrow-derived mesenchymal stromal cells (MSC) based on gene expression profiling of functionally defined MSC subsets. Cytotherapy 11(2):114–128. doi: 10.1080/14653240802716590 PubMedCrossRefGoogle Scholar
  22. 22.
    Arufe MC, De la Fuente A, Fuentes I et al (2010) Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes. J Cell Biochem 111(4):834–845. doi: 10.1002/jcb.22768 PubMedCrossRefGoogle Scholar
  23. 23.
    Colter DC, Sekiya I, Prockop DJ (2001) Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci USA 98(14):7841–7845. doi: 10.1073/pnas.141221698 PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Prockop DJ, Sekiya I, Colter DC (2001) Isolation and characterization of rapidly self-renewing stem cells from cultures of human marrow stromal cells. Cytotherapy 3(5):393–396. doi: 10.1080/146532401753277229 PubMedCrossRefGoogle Scholar
  25. 25.
    Lee RH, Hsu SC, Munoz J et al (2006) A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice. Blood 107(5):2153–2161. doi: 10.1182/blood-2005-07-2701 PubMedCrossRefGoogle Scholar
  26. 26.
    Iinuma S, Aikawa E, Tamai K et al (2015) Transplanted bone marrow-derived circulating PDGFRalpha+ cells restore type VII collagen in recessive dystrophic epidermolysis bullosa mouse skin graft. J Immunol 194(4):1996–2003. doi: 10.4049/jimmunol.1400914 PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Mabuchi Y, Morikawa S, Harada S et al (2013) LNGFR(+)THY-1(+)VCAM-1(hi +) cells reveal functionally distinct subpopulations in mesenchymal stem cells. Stem cell reports 1(2):152–165. doi: 10.1016/j.stemcr.2013.06.001 PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Seeger FH, Rasper T, Koyanagi M et al (2009) CXCR4 expression determines functional activity of bone marrow-derived mononuclear cells for therapeutic neovascularization in acute ischemia. Arterioscler Thromb Vasc Biol 29(11):1802–1809. doi: 10.1161/ATVBAHA.109.194688 PubMedCrossRefGoogle Scholar
  29. 29.
    Lane SW, Williams DA, Watt FM (2014) Modulating the stem cell niche for tissue regeneration. Nat Biotech 32(8):795–803. doi: 10.1038/nbt.2978 CrossRefGoogle Scholar
  30. 30.
    Jiang Y, Jahagirdar BN, Reinhardt RL et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418(6893):41–49. doi: 10.1038/nature00870 PubMedCrossRefGoogle Scholar
  31. 31.
    Kuroda Y, Kitada M, Wakao S et al (2010) Unique multipotent cells in adult human mesenchymal cell populations. Proc Natl Acad Sci USA 107(19):8639–8643. doi: 10.1073/pnas.0911647107 PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Han B, Li J, Li Z et al (2013) Trichostatin A stabilizes the expression of pluripotent genes in human mesenchymal stem cells during ex vivo expansion. PLoS One 8(11):e81781. doi: 10.1371/journal.pone.0081781 PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Li Z, Liu C, Xie Z et al (2011) Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation. PLoS One 6(6):e20526. doi: 10.1371/journal.pone.0020526 PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Ning H, Lin G, Lue TF et al (2011) Mesenchymal stem cell marker Stro-1 is a 75 kd endothelial antigen. Biochem Biophys Res Comm 413(2):353–357. doi: 10.1016/j.bbrc.2011.08.104 PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Lin G, Liu G, Banie L et al (2011) Tissue distribution of mesenchymal stem cell marker Stro-1. Stem Cells Dev 20(10):1747–1752. doi: 10.1089/scd.2010.0564 PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Psaltis PJ, Paton S, See F et al (2010) Enrichment for STRO-1 expression enhances the cardiovascular paracrine activity of human bone marrow-derived mesenchymal cell populations. J Cell Physiol 223(2):530–540. doi: 10.1002/jcp.22081 PubMedGoogle Scholar
  37. 37.
    Bensidhoum M, Chapel A, Francois S et al (2004) Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment. Blood 103(9):3313–3319. doi: 10.1182/blood-2003-04-1121 PubMedCrossRefGoogle Scholar
  38. 38.
    Samsonraj RM, Rai B, Sathiyanathan P et al (2015) Establishing criteria for human mesenchymal stem cell potency. Stem Cells 33(6):1878–1891. doi: 10.1002/stem.1982 PubMedCrossRefGoogle Scholar
  39. 39.
    Zannettino AC, Paton S, Kortesidis A et al (2007) Human mulipotential mesenchymal/stromal stem cells are derived from a discrete subpopulation of STRO-1bright/CD34/CD45(-)/glycophorin-A-bone marrow cells. Haematologica 92(12):1707–1708. doi: 10.3324/haematol.11691 PubMedCrossRefGoogle Scholar
  40. 40.
    Simmons PJ, Torokstorb B (1991) Identification of stromal cell precursors in human bone-marrow by a novel monoclonal-antibody, Stro-1. Blood 78(1):55–62PubMedGoogle Scholar
  41. 41.
    Martens TP, See F, Schuster MD et al (2006) Mesenchymal lineage precursor cells induce vascular network formation in ischemic myocardium. Nature Clin Pract Cardiovasc Med 3(Suppl 1):S18–S22. doi: 10.1038/ncpcardio0404 CrossRefGoogle Scholar
  42. 42.
    Thomson TM, Rettig WJ, Chesa PG et al (1988) Expression of human nerve growth factor receptor on cells derived from all three germ layers. Exp Cell Res 174(2):533–539PubMedCrossRefGoogle Scholar
  43. 43.
    Busser H, Najar M, Raicevic G et al (2015) Isolation and characterization of human mesenchymal stromal cell subpopulations: comparison of bone marrow and adipose tissue. Stem Cells Dev 24(18):2142–2157. doi: 10.1089/scd.2015.0172 PubMedCrossRefGoogle Scholar
  44. 44.
    Quirici N, Soligo D, Bossolasco P et al (2002) Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Exp Hematol 30(7):783–791PubMedCrossRefGoogle Scholar
  45. 45.
    Iso Y, Yamaya S, Sato T et al (2012) Distinct mobilization of circulating CD271+ mesenchymal progenitors from hematopoietic progenitors during aging and after myocardial infarction. Stem Cells Transl Med 1(6):462–468. doi: 10.5966/sctm.2011-0051 PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Cuthbert R, Boxall SA, Tan HB et al (2012) Single-platform quality control assay to quantify multipotential stromal cells in bone marrow aspirates prior to bulk manufacture or direct therapeutic use. Cytotherapy 14(4):431–440. doi: 10.3109/14653249.2011.651533 PubMedCrossRefGoogle Scholar
  47. 47.
    Cuthbert RJ, Giannoudis PV, Wang XN et al (2015) Examining the feasibility of clinical grade CD271+ enrichment of mesenchymal stromal cells for bone regeneration. PLoS One 10(3):e0117855. doi: 10.1371/journal.pone.0117855 PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Churchman SM, Ponchel F, Boxall SA et al (2012) Transcriptional profile of native CD271+ multipotential stromal cells: evidence for multiple fates, with prominent osteogenic and Wnt pathway signaling activity. Arthritis Rheum 64(8):2632–2643. doi: 10.1002/art.34434 PubMedCrossRefGoogle Scholar
  49. 49.
    Mifune Y, Matsumoto T, Murasawa S et al (2013) Therapeutic superiority for cartilage repair by CD271-positive marrow stromal cell transplantation. Cell Transplant 22(7):1201–1211. doi: 10.3727/096368912X657378 PubMedCrossRefGoogle Scholar
  50. 50.
    Kuci S, Kuci Z, Kreyenberg H et al (2010) CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties. Haematologica 95(4):651–659. doi: 10.3324/haematol.2009.015065 PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Li H, Ghazanfari R, Zacharaki D et al (2014) Low/negative expression of PDGFR-alpha identifies the candidate primary mesenchymal stromal cells in adult human bone marrow. Stem Cell Report 3(6):965–974. doi: 10.1016/j.stemcr.2014.09.018 CrossRefGoogle Scholar
  52. 52.
    Battula VL, Treml S, Bareiss PM et al (2009) Isolation of functionally distinct mesenchymal stem cell subsets using antibodies against CD56, CD271, and mesenchymal stem cell antigen-1. Haematologica 94(2):173–184. doi: 10.3324/haematol.13740 PubMedCrossRefGoogle Scholar
  53. 53.
    Noort WA, Oerlemans MI, Rozemuller H et al (2012) Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement after transplantation. J Cell Mol Med 16(8):1827–1839. doi: 10.1111/j.1582-4934.2011.01455.x PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Latifi-Pupovci H, Kuci Z, Wehner S et al (2015) In vitro migration and proliferation (“wound healing”) potential of mesenchymal stromal cells generated from human CD271(+) bone marrow mononuclear cells. J Transl Med 13:315. doi: 10.1186/s12967-015-0676-9 PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Duff SE, Li C, Garland JM et al (2003) CD105 is important for angiogenesis: evidence and potential applications. FASEB J Off Publ Fed Am Soc Exp Biol 17(9):984–992. doi: 10.1096/fj.02-0634rev Google Scholar
  56. 56.
    Gaebel R, Furlani D, Sorg H et al (2011) Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration. PLoS One 6(2):e15652. doi: 10.1371/journal.pone.0015652 PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Pierelli L, Bonanno G, Rutella S et al (2001) CD105 (endoglin) expression on hematopoietic stem/progenitor cells. Leuk Lymph 42(6):1195–1206. doi: 10.3109/10428190109097744 CrossRefGoogle Scholar
  58. 58.
    Noiseux N, Gnecchi M, Lopez-Ilasaca M et al (2006) Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Mol Ther J Am Soc Gene Ther 14(6):840–850. doi: 10.1016/j.ymthe.2006.05.016 CrossRefGoogle Scholar
  59. 59.
    Silva GV, Litovsky S, Assad JA et al (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111(2):150–156. doi: 10.1161/01.CIR.0000151812.86142.45 PubMedCrossRefGoogle Scholar
  60. 60.
    Conconi MT, Burra P, Di Liddo R et al (2006) CD105(+) cells from Wharton’s jelly show in vitro and in vivo myogenic differentiative potential. Int J Mol Med 18(6):1089–1096PubMedGoogle Scholar
  61. 61.
    Roura S, Farre J, Soler-Botija C et al (2006) Effect of aging on the pluripotential capacity of human CD105 +mesenchymal stem cells. Eur J Heart Fail 8(6):555–563. doi: 10.1016/j.ejheart.2005.11.006 PubMedCrossRefGoogle Scholar
  62. 62.
    Ranganath SH, Levy O, Inamdar MS et al (2012) Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell 10(3):244–258. doi: 10.1016/j.stem.2012.02.005 PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Li N, Wang C, Jia L et al (2014) Heart regeneration, stem cells, and cytokines. Regen Med Res 2(1):6. doi: 10.1186/2050-490X-2-6 PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Iohara K, Imabayashi K, Ishizaka R et al (2011) Complete pulp regeneration after pulpectomy by transplantation of CD105 + stem cells with stromal cell-derived factor-1. Tissue Eng Part A 17(15–16):1911–1920. doi: 10.1089/ten.TEA.2010.0615 PubMedCrossRefGoogle Scholar
  65. 65.
    Pettine KA, Murphy MB, Suzuki RK et al (2015) Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cell 33(1):146–156. doi: 10.1002/stem.1845 CrossRefGoogle Scholar
  66. 66.
    Alon R, Kassner PD, Carr MW et al (1995) The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. J Cell Biol 128(6):1243–1253PubMedCrossRefGoogle Scholar
  67. 67.
    Schaffler A, Buchler C (2007) Concise review: adipose tissue-derived stromal cells–basic and clinical implications for novel cell-based therapies. Stem Cell 25(4):818–827. doi: 10.1634/stemcells.2006-0589 CrossRefGoogle Scholar
  68. 68.
    Fukiage K, Aoyama T, Shibata KR et al (2008) Expression of vascular cell adhesion molecule-1 indicates the differentiation potential of human bone marrow stromal cells. Biochem Biophys Res Comm 365(3):406–412. doi: 10.1016/j.bbrc.2007.10.149 PubMedCrossRefGoogle Scholar
  69. 69.
    Gronthos S, Zannettino AC, Hay SJ et al (2003) Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J Cell Sci 116(Pt 9):1827–1835PubMedCrossRefGoogle Scholar
  70. 70.
    Fujita R, Tamai K, Aikawa E et al (2015) Endogenous mesenchymal stromal cells in bone marrow are required to preserve muscle function in mdx mice. Stem Cell 33(3):962–975. doi: 10.1002/stem.1900 CrossRefGoogle Scholar
  71. 71.
    Ren G, Zhao X, Zhang L et al (2010) Inflammatory Cytokine-Induced Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 in Mesenchymal Stem Cells Are Critical for Immunosuppression. J Immunol 184(5):2321–2328. doi: 10.4049/jimmunol.0902023 PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Castro-Manrreza ME, Montesinos JJ (2015) Immunoregulation by mesenchymal stem cells: biological aspects and clinical applications. J Immunol Res 2015:394917. doi: 10.1155/2015/394917 PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Shih IM (1999) The role of CD146 (Mel-CAM) in biology and pathology. J Pathol 189(1):4–11. doi: 10.1002/(SICI)1096-9896(199909)189:1<4:AID-PATH332>3.0.CO;2-P PubMedCrossRefGoogle Scholar
  74. 74.
    Martin-Rendon E, Sweeney D, Lu F et al (2008) 5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies. Vox Sang 95(2):137–148. doi: 10.1111/j.1423-0410.2008.01076.x PubMedCrossRefGoogle Scholar
  75. 75.
    Rider DA, Dombrowski C, Sawyer AA et al (2008) Autocrine fibroblast growth factor 2 increases the multipotentiality of human adipose-derived mesenchymal stem cells. Stem Cells 26(6):1598–1608. doi: 10.1634/stemcells.2007-0480 PubMedCrossRefGoogle Scholar
  76. 76.
    Maleki M, Ghanbarvand F, Reza Behvarz M et al (2014) Comparison of mesenchymal stem cell markers in multiple human adult stem cells. Int J Stem Cell 7(2):118–126. doi: 10.15283/ijsc.2014.7.2.118 CrossRefGoogle Scholar
  77. 77.
    Espagnolle N, Guilloton F, Deschaseaux F et al (2014) CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment. J Cell Mol Med 18(1):104–114. doi: 10.1111/jcmm.12168 PubMedCrossRefGoogle Scholar
  78. 78.
    Crisan M, Yap S, Casteilla L et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313. doi: 10.1016/j.stem.2008.07.003 PubMedCrossRefGoogle Scholar
  79. 79.
    Sacchetti B, Funari A, Michienzi S et al (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131(2):324–336. doi: 10.1016/j.cell.2007.08.025 PubMedCrossRefGoogle Scholar
  80. 80.
    Blocki A, Wang Y, Koch M et al (2013) Not all MSCs can act as pericytes: functional in vitro assays to distinguish pericytes from other mesenchymal stem cells in angiogenesis. Stem Cells Dev 22(17):2347–2355. doi: 10.1089/scd.2012.0415 PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3(3):229–230. doi: 10.1016/j.stem.2008.08.008 PubMedCrossRefGoogle Scholar
  82. 82.
    Baksh D, Yao R, Tuan RS (2007) Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 25(6):1384–1392. doi: 10.1634/stemcells.2006-0709 PubMedCrossRefGoogle Scholar
  83. 83.
    Russell KC, Phinney DG, Lacey MR et al (2010) In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage potential of mesenchymal stem cells reveals a complex hierarchy of lineage commitment. Stem Cell 28(4):788–798. doi: 10.1002/stem.312 CrossRefGoogle Scholar
  84. 84.
    Sorrentino A, Ferracin M, Castelli G et al (2008) Isolation and characterization of CD146 + multipotent mesenchymal stromal cells. Exp Hematol 36(8):1035–1046. doi: 10.1016/j.exphem.2008.03.004 PubMedCrossRefGoogle Scholar
  85. 85.
    Corselli M, Chin CJ, Parekh C et al (2013) Perivascular support of human hematopoietic stem/progenitor cells. Blood 121(15):2891–2901. doi: 10.1182/blood-2012-08-451864 PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Park TS, Gavina M, Chen CW et al (2011) Placental perivascular cells for human muscle regeneration. Stem Cell Dev 20(3):451–463. doi: 10.1089/scd.2010.0354 CrossRefGoogle Scholar
  87. 87.
    Chen CW, Okada M, Proto JD et al (2013) Human pericytes for ischemic heart repair. Stem Cell 31(2):305–316. doi: 10.1002/stem.1285 CrossRefGoogle Scholar
  88. 88.
    Houlihan DD, Mabuchi Y, Morikawa S et al (2012) Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and PDGFR-α. Nat Protoc 7(12):2103–2111. doi: 10.1038/nprot.2012.125 PubMedCrossRefGoogle Scholar
  89. 89.
    Hoffman AM, Paxson JA, Mazan MR et al (2011) Lung-derived mesenchymal stromal cell post-transplantation survival, persistence, paracrine expression, and repair of elastase-injured lung. Stem Cell Dev 20(10):1779–1792. doi: 10.1089/scd.2011.0105 CrossRefGoogle Scholar
  90. 90.
    Jiang MH, Li G, Liu J et al (2015) Nestin(+) kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury. Biomaterials 50:56–66. doi: 10.1016/j.biomaterials.2015.01.029 PubMedCrossRefGoogle Scholar
  91. 91.
    Morikawa S, Mabuchi Y, Kubota Y et al (2009) Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med 206(11):2483–2496. doi: 10.1084/jem.20091046 PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Pinho S, Lacombe J, Hanoun M et al (2013) PDGFRalpha and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. J Exp Med 210(7):1351–1367. doi: 10.1084/jem.20122252 PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Fathke C, Wilson L, Hutter J et al (2004) Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cell 22(5):812–822. doi: 10.1634/stemcells.22-5-812 CrossRefGoogle Scholar
  94. 94.
    Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22(10):1276–1312. doi: 10.1101/gad.1653708 PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Hellstrom M, Kalen M, Lindahl P et al (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126(14):3047–3055PubMedGoogle Scholar
  96. 96.
    Ball SG, Shuttleworth CA, Kielty CM (2007) Platelet-derived growth factor receptor-alpha is a key determinant of smooth muscle alpha-actin filaments in bone marrow-derived mesenchymal stem cells. Int J Biochem Cell Biol 39(2):379–391. doi: 10.1016/j.biocel.2006.09.005 PubMedCrossRefGoogle Scholar
  97. 97.
    Ball SG, Shuttleworth A, Kielty CM (2012) Inhibition of platelet-derived growth factor receptor signaling regulates Oct4 and Nanog expression, cell shape, and mesenchymal stem cell potency. Stem Cell 30(3):548–560. doi: 10.1002/stem.1015 CrossRefGoogle Scholar
  98. 98.
    Rajkumar VS, Shiwen X, Bostrom M et al (2006) Platelet-Derived Growth Factor-β Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing. Am J Pathol 169(6):2254–2265. doi: 10.2353/ajpath.2006.060196 PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Tokunaga A, Oya T, Ishii Y et al (2008) PDGF receptor beta is a potent regulator of mesenchymal stromal cell function. J Bone Miner Res Off J Am Soc Bone Miner Res 23(9):1519–1528. doi: 10.1359/jbmr.080409 CrossRefGoogle Scholar
  100. 100.
    Tigges U, Komatsu M, Stallcup WB (2013) Adventitial pericyte progenitor/mesenchymal stem cells participate in the restenotic response to arterial injury. J Vasc Res 50(2):134–144. doi: 10.1159/000345524000345524 PubMedCrossRefGoogle Scholar
  101. 101.
    Ball SG, Worthington JJ, Canfield AE et al (2014) Mesenchymal stromal cells: inhibiting PDGF receptors or depleting fibronectin induces mesodermal progenitors with endothelial potential. Stem Cell 32(3):694–705. doi: 10.1002/stem.1538 CrossRefGoogle Scholar
  102. 102.
    Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60(4):585–595PubMedCrossRefGoogle Scholar
  103. 103.
    Mendez-Ferrer S, Michurina TV, Ferraro F et al (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466(7308):829–834. doi: 10.1038/nature09262 PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Isern J, Martin-Antonio B, Ghazanfari R et al (2013) Self-renewing human bone marrow mesenspheres promote hematopoietic stem cell expansion. Cell Report 3(5):1714–1724. doi: 10.1016/j.celrep.2013.03.041 CrossRefGoogle Scholar
  105. 105.
    Wan M, Li C, Zhen G et al (2012) Injury-activated transforming growth factor beta controls mobilization of mesenchymal stem cells for tissue remodeling. Stem Cells 30(11):2498–2511. doi: 10.1002/stem.1208 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Zhen G, Wen C, Jia X et al (2013) Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med 19(6):704–712. doi: 10.1038/nm.3143 PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Follenzi A, Raut S, Merlin S et al (2012) Role of bone marrow transplantation for correcting hemophilia A in mice. Blood 119(23):5532–5542. doi: 10.1182/blood-2011-07-367680 PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Ip JE, Wu Y, Huang J et al (2007) Mesenchymal stem cells use integrin beta1 not CXC chemokine receptor 4 for myocardial migration and engraftment. Mol Biol Cell 18(8):2873–2882. doi: 10.1091/mbc.E07-02-0166 PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Shi M, Li J, Liao L et al (2007) Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematol-Hematol J 92(7):897–904. doi: 10.3324/haematol.10669 CrossRefGoogle Scholar
  110. 110.
    Potapova IA, Brink PR, Cohen IS et al (2008) Culturing of human mesenchymal stem cells as three-dimensional aggregates induces functional expression of CXCR4 that regulates adhesion to endothelial cells. J Biol Chem 283(19):13100–13107. doi: 10.1074/jbc.M800184200 PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Liu H, Liu S, Li Y et al (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):e34608. doi: 10.1371/journal.pone.0034608 PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Cheng Z, Ou L, Zhou X et al (2008) Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther J Am Soc Gene Ther 16(3):571–579. doi: 10.1038/sj.mt.6300374 CrossRefGoogle Scholar
  113. 113.
    Wang Z, Wang Y, Wang Z et al (2015) Engineered mesenchymal stem cells with enhanced tropism and paracrine secretion of cytokines and growth factors to treat traumatic brain injury. Stem Cell 33(2):456–467. doi: 10.1002/stem.1878 CrossRefGoogle Scholar
  114. 114.
    Yu Q, Liu L, Lin J et al (2015) SDF-1alpha/CXCR4 Axis Mediates The Migration of Mesenchymal Stem Cells to The Hypoxic-Ischemic Brain Lesion in A Rat Model. Cell J 16(4):440–447PubMedPubMedCentralGoogle Scholar
  115. 115.
    Du Z, Wei C, Yan J et al (2013) Mesenchymal stem cells overexpressing C-X-C chemokine receptor type 4 improve early liver regeneration of small-for-size liver grafts. Liver Transpl Off Publ Am Assoc Study Liver Dis Int Liver Transpl Soc 19(2):215–225. doi: 10.1002/lt.23577 Google Scholar
  116. 116.
    Gang EJ, Bosnakovski D, Figueiredo CA et al (2007) SSEA-4 identifies mesenchymal stem cells from bone marrow. Blood 109(4):1743–1751. doi: 10.1182/blood-2005-11-010504 PubMedCrossRefGoogle Scholar
  117. 117.
    Hamamoto H, Gorman JH 3rd, Ryan LP et al (2009) Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage. Annals Thorac Surg 87(3):794–801. doi: 10.1016/j.athoracsur.2008.11.057 CrossRefGoogle Scholar
  118. 118.
    Ortiz LA, Dutreil M, Fattman C et al (2007) Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA 104(26):11002–11007. doi: 10.1073/pnas.0704421104 PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Herrera MB, Bussolati B, Bruno S et al (2007) Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kidney Int 72(4):430–441. doi: 10.1038/sj.ki.5002334 PubMedCrossRefGoogle Scholar
  120. 120.
    Lee RH, Seo MJ, Pulin AA et al (2009) The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. Blood 113(4):816–826. doi: 10.1182/blood-2007-12-128702 PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Zhou BO, Yue R, Murphy MM et al (2014) Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell 15(2):154–168. doi: 10.1016/j.stem.2014.06.008 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  1. 1.School of Life SciencesTsinghua UniversityBeijingChina
  2. 2.The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at ShenzhenTsinghua UniversityShenzhenChina
  3. 3.Department of General SurgeryQingdao Municipal HospitalQingdaoChina

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