Skip to main content

MicroRNAs in Mesenchymal Stem Cells

  • Chapter
  • First Online:

Abstract

Mesenchymal stem cells (MSC) are adult stem cells that can expand noticeably in culture and are identified in almost every tissue type including early stages of development as well as adult tissues. This wide-ranging distribution of sources along with their genetic stability, compatibility with tissue engineering principles, reproducibility of features, immunoregulatory properties and multilineage potential has led them to be considered as prospective curative candidates for numerous diseases and degenerative purposes. MicroRNAs (miRs) are a class of small non-coding single-stranded RNAs of 19–23 nucleotides that originate from a precursor of approximately 70 nucleotides. Studies with stem cells show a complicated system of miRs regulating main transcription factors and other genes, which sequentially define cell fate. In particular, newly recognized miRs differentiation signatures for MSC designate the presence of distinctive miR patterns in progenitors and terminally differentiated cells, suggesting that such signatures may act as a marker to delineate and track rare cell populations. Recently, several studies have reported the ability of miRs to regulate the differentiation, identity, behavior and self-renewal of MSC. Regulation of MSC homing, reparative and therapeutic efficacies by miRs has been also reported. The overall goal of this chapter is to shed some light on the regulatory role of miRs in different MSC, as well as the putative role of miRs in regulating the therapeutic efficacy of MSC in the pathophysiology of several diseases.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001;98(8):2396–402.

    PubMed  CAS  Google Scholar 

  2. da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006;119(Pt 11):2204–13.

    PubMed  Google Scholar 

  3. Elnakish MT, Hassan F, Dakhlallah D, Marsh CB, Alhaider IA, Khan M. Mesenchymal stem cells for cardiac regeneration: translation to bedside reality. Stem Cells Int. 2012;2012:646038.

    PubMed  Google Scholar 

  4. Doi M, Nagano A, Nakamura Y. Molecular cloning and characterization of a novel gene, EMILIN-5, and its possible involvement in skeletal development. Biochem Biophys Res Commun. 2004;313(4):888–93.

    PubMed  CAS  Google Scholar 

  5. Qi H, Aguiar DJ, Williams SM, La Pean A, Pan W, Verfaillie CM. Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells. Proc Natl Acad Sci USA. 2003;100(6):3305–10.

    PubMed  CAS  Google Scholar 

  6. Lakshmipathy U, Hart RP. Concise review: MicroRNA expression in multipotent mesenchymal stromal cells. Stem Cells. 2008;26(2):356–63.

    PubMed  CAS  Google Scholar 

  7. Giraud-Triboult K, Rochon-Beaucourt C, Nissan X, Champon B, Aubert S, Pietu G. Combined mRNA and microRNA profiling reveals that miR-148a and miR-20b control human mesenchymal stem cell phenotype via EPAS1. Physiol Genomics. 2011;43(2):77–86.

    PubMed  CAS  Google Scholar 

  8. Guo L, Zhao RC, Wu Y. The role of microRNAs in self-renewal and differentiation of mesenchymal stem cells. Exp Hematol. 2011;39(6):608–16.

    PubMed  CAS  Google Scholar 

  9. Wang Y, Jiang XL, Yang SC, Lin X, He Y, Yan C, Wu L, Chen GQ, Wang ZY, Wu Q. MicroRNAs in the regulation of interfacial behaviors of MSCs cultured on microgrooved surface pattern. Biomaterials. 2011;32(35):9207–17.

    PubMed  CAS  Google Scholar 

  10. Lim PK, Patel SA, Gregory LA, Rameshwar P. Neurogenesis: role for microRNAs and mesenchymal stem cells in pathological states. Curr Med Chem. 2010;17(20):2159–67.

    PubMed  CAS  Google Scholar 

  11. Pillai MM, Yang X, Balakrishnan I, Bemis L, Torok-Storb B. MiR-886-3p down regulates CXCL12 (SDF1) expression in human marrow stromal cells. PLoS One. 2010;5(12):e14304.

    PubMed  CAS  Google Scholar 

  12. Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 2005;37(7):766–70.

    PubMed  CAS  Google Scholar 

  13. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20.

    PubMed  CAS  Google Scholar 

  14. Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B, Rigoutsos I. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell. 2006;126(6):1203–17.

    PubMed  CAS  Google Scholar 

  15. Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, Lander ES, Kellis M. Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature. 2005;434(7031):338–45.

    PubMed  CAS  Google Scholar 

  16. Bhardwaj A, Singh S, Singh AP. MicroRNA-based cancer therapeutics: big hope from small RNAs. Mol Cell Pharmacol. 2010;2(5):213–9.

    PubMed  CAS  Google Scholar 

  17. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature. 2005;435(7043):828–33.

    PubMed  CAS  Google Scholar 

  18. Seitz H, Royo H, Bortolin ML, Lin SP, Ferguson-Smith AC, Cavaille J. A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res. 2004;14(9):1741–8.

    PubMed  CAS  Google Scholar 

  19. Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG, Nishikura K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science. 2007;315(5815):1137–40.

    PubMed  CAS  Google Scholar 

  20. Luciano DJ, Mirsky H, Vendetti NJ, Maas S. RNA editing of a miRNA precursor. RNA. 2004;10(8):1174–7.

    PubMed  CAS  Google Scholar 

  21. Ruby JG, Jan CH, Bartel DP. Intronic microRNA precursors that bypass Drosha processing. Nature. 2007;448(7149):83–6.

    PubMed  CAS  Google Scholar 

  22. Ying SY, Lin SL. Intronic microRNAs. Biochem Biophys Res Commun. 2005;326(3):515–20.

    PubMed  CAS  Google Scholar 

  23. Cheng AM, Byrom MW, Shelton J, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 2005;33(4):1290–7.

    PubMed  CAS  Google Scholar 

  24. Mansfield JH, Harfe BD, Nissen R, Obenauer J, Srineel J, Chaudhuri A, Farzan-Kashani R, Zuker M, Pasquinelli AE, Ruvkun G, Sharp PA, Tabin CJ, McManus MT. MicroRNA-responsive ‘sensor’ transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet. 2004;36(10):1079–83.

    PubMed  CAS  Google Scholar 

  25. Nakahara K, Kim K, Sciulli C, Dowd SR, Minden JS, Carthew RW. Targets of microRNA regulation in the Drosophila oocyte proteome. Proc Natl Acad Sci USA. 2005;102(34):12023–8.

    PubMed  CAS  Google Scholar 

  26. O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435(7043):839–43.

    PubMed  Google Scholar 

  27. Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005;120(1):21–4.

    PubMed  CAS  Google Scholar 

  28. Goff LA, Boucher S, Ricupero CL, Fenstermacher S, Swerdel M, Chase LG, Adams CC, Chesnut J, Lakshmipathy U, Hart RP. Differentiating human multipotent mesenchymal stromal cells regulate microRNAs: prediction of microRNA regulation by PDGF during osteogenesis. Exp Hematol. 2008;36(10):1354–69.

    PubMed  CAS  Google Scholar 

  29. Lakshmipathy U, Love B, Goff LA, Jornsten R, Graichen R, Hart RP, Chesnut JD. MicroRNA expression pattern of undifferentiated and differentiated human embryonic stem cells. Stem Cells Dev. 2007;16(6):1003–16.

    PubMed  CAS  Google Scholar 

  30. de Peppo GM, Svensson S, Lenneras M, Synnergren J, Stenberg J, Strehl R, Hyllner J, Thomsen P, Karlsson C. Human embryonic mesodermal progenitors highly resemble human mesenchymal stem cells and display high potential for tissue engineering applications. Tissue Eng Part A. 2010;16(7):2161–82.

    PubMed  Google Scholar 

  31. Lian Q, Lye E, Suan Yeo K, Khia Way Tan E, Salto-Tellez M, Liu TM, Palanisamy N, El Oakley RM, Lee EH, Lim B, Lim SK. Derivation of clinically compliant MSCs from CD105+, CD24− differentiated human ESCs. Stem Cells. 2007;25(2):425–36.

    PubMed  CAS  Google Scholar 

  32. Olivier EN, Rybicki AC, Bouhassira EE. Differentiation of human embryonic stem cells into bipotent mesenchymal stem cells. Stem Cells. 2006;24(8):1914–22.

    PubMed  CAS  Google Scholar 

  33. Khan M, Meduru S, Mohan IK, Kuppusamy ML, Wisel S, Kulkarni A, Rivera BK, Hamlin RL, Kuppusamy P. Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart. J Mol Cell Cardiol. 2009;47(2):275–87.

    PubMed  CAS  Google Scholar 

  34. Kim YJ, Bae SW, Yu SS, Bae YC, Jung JS. miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res. 2009;24(5):816–25.

    PubMed  CAS  Google Scholar 

  35. Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka-Kanesaki Y, Suda T, Fukuda T, Katagiri T, Kondoh Y, Amemiya T, Tashiro H, Okazaki Y. miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett. 2009;583(13):2263–8.

    PubMed  CAS  Google Scholar 

  36. Li H, Xie H, Liu W, Hu R, Huang B, Tan YF, Xu K, Sheng ZF, Zhou HD, Wu XP, Luo XH. A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest. 2009;119(12):3666–77.

    PubMed  CAS  Google Scholar 

  37. Schoolmeesters A, Eklund T, Leake D, Vermeulen A, Smith Q, Force Aldred S, Fedorov Y. Functional profiling reveals critical role for miRNA in differentiation of human mesenchymal stem cells. PLoS One. 2009;4(5):e5605.

    PubMed  Google Scholar 

  38. Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB. Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem. 2009;284(23):15676–84.

    PubMed  CAS  Google Scholar 

  39. Gao J, Yang T, Han J, Yan K, Qiu X, Zhou Y, Fan Q, Ma B. MicroRNA expression during osteogenic differentiation of human multipotent mesenchymal stromal cells from bone marrow. J Cell Biochem. 2011;112(7):1844–56.

    PubMed  CAS  Google Scholar 

  40. Mizuno Y, Yagi K, Tokuzawa Y, Kanesaki-Yatsuka Y, Suda T, Katagiri T, Fukuda T, Maruyama M, Okuda A, Amemiya T, Kondoh Y, Tashiro H, Okazaki Y. miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation. Biochem Biophys Res Commun. 2008;368(2):267–72.

    PubMed  CAS  Google Scholar 

  41. Eskildsen T, Taipaleenmaki H, Stenvang J, Abdallah BM, Ditzel N, Nossent AY, Bak M, Kauppinen S, Kassem M. MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. Proc Natl Acad Sci USA. 2011;108(15):6139–44.

    PubMed  Google Scholar 

  42. Li Z, Hassan MQ, Volinia S, van Wijnen AJ, Stein JL, Croce CM, Lian JB, Stein GS. A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc Natl Acad Sci USA. 2008;105(37):13906–11.

    PubMed  CAS  Google Scholar 

  43. Inose H, Ochi H, Kimura A, Fujita K, Xu R, Sato S, Iwasaki M, Sunamura S, Takeuchi Y, Fukumoto S, Saito K, Nakamura T, Siomi H, Ito H, Arai Y, Shinomiya K, Takeda S. A microRNA regulatory mechanism of osteoblast differentiation. Proc Natl Acad Sci USA. 2009;106(49):20794–9.

    PubMed  CAS  Google Scholar 

  44. Huang J, Zhao L, Xing L, Chen D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 2010;28(2):357–64.

    PubMed  Google Scholar 

  45. Luzi E, Marini F, Sala SC, Tognarini I, Galli G, Brandi ML. Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor. J Bone Miner Res. 2008;23(2):287–95.

    PubMed  CAS  Google Scholar 

  46. Han J, Yang T, Gao J, Wu J, Qiu X, Fan Q, Ma B. Specific microRNA expression during chondrogenesis of human mesenchymal stem cells. Int J Mol Med. 2010;25(3):377–84.

    PubMed  CAS  Google Scholar 

  47. Yang B, Guo H, Zhang Y, Dong S, Ying D. The microRNA expression profiles of mouse mesenchymal stem cell during chondrogenic differentiation. BMB Rep. 2011;44(1):28–33.

    PubMed  CAS  Google Scholar 

  48. Miyaki S, Nakasa T, Otsuki S, Grogan SP, Higashiyama R, Inoue A, Kato Y, Sato T, Lotz MK, Asahara H. MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses. Arthritis Rheum. 2009;60(9):2723–30.

    PubMed  CAS  Google Scholar 

  49. Tuddenham L, Wheeler G, Ntounia-Fousara S, Waters J, Hajihosseini MK, Clark I, Dalmay T. The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells. FEBS Lett. 2006;580(17):4214–7.

    PubMed  CAS  Google Scholar 

  50. Lin EA, Kong L, Bai XH, Luan Y, Liu CJ. miR-199a, a bone morphogenic protein 2-responsive MicroRNA, regulates chondrogenesis via direct targeting to Smad1. J Biol Chem. 2009;284(17):11326–35.

    PubMed  CAS  Google Scholar 

  51. Kim YJ, Hwang SJ, Bae YC, Jung JS. MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue. Stem Cells. 2009;27(12):3093–102.

    PubMed  CAS  Google Scholar 

  52. Sun F, Wang J, Pan Q, Yu Y, Zhang Y, Wan Y, Li X, Hong A. Characterization of function and regulation of miR-24-1 and miR-31. Biochem Biophys Res Commun. 2009;380(3):660–5.

    PubMed  CAS  Google Scholar 

  53. Yang Z, Bian C, Zhou H, Huang S, Wang S, Liao L, Zhao RC. MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1. Stem Cells Dev. 2011;20(2):259–67.

    PubMed  CAS  Google Scholar 

  54. Shan ZX, Lin QX, Yu XY, Deng CY, Li XH, Zhang XC, Liu XY, Fu YH. MicroRNAs can be expressed in cardiomyocyte-like cells differentiated from human mesenchymal stem cells. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27(12):1813–6.

    PubMed  CAS  Google Scholar 

  55. Kim HK, Lee YS, Sivaprasad U, Malhotra A, Dutta A. Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol. 2006;174(5):677–87.

    PubMed  CAS  Google Scholar 

  56. Naguibneva I, Ameyar-Zazoua M, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M, Cuvellier S, Harel-Bellan A. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol. 2006;8(3):278–84.

    PubMed  CAS  Google Scholar 

  57. Liu JL, Jiang L, Lin QX, Deng CY, Mai LP, Zhu JN, Li XH, Yu XY, Lin SG, Shan ZX. MicroRNA 16 enhances differentiation of human bone marrow mesenchymal stem cells in a cardiac niche toward myogenic phenotypes in vitro. Life Sci. 2012;90(25–26):1020–6.

    PubMed  CAS  Google Scholar 

  58. Zhang LL, Liu JJ, Liu F, Liu WH, Wang YS, Zhu B, Yu B. MiR-499 induces cardiac differentiation of rat mesenchymal stem cells through wnt/beta-catenin signaling pathway. Biochem Biophys Res Commun. 2012;420(4):875–81.

    PubMed  CAS  Google Scholar 

  59. Cai B, Li J, Wang J, Luo X, Ai J, Liu Y, Wang N, Liang H, Zhang M, Chen N, Wang G, Xing S, Zhou X, Yang B, Wang X, Lu Y. microRNA-124 regulates cardiomyocyte differentiation of bone marrow-derived mesenchymal stem cells via targeting STAT3 signaling. Stem Cells. 2012;30(8):1746–55.

    PubMed  CAS  Google Scholar 

  60. Greco SJ, Rameshwar P. MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. Proc Natl Acad Sci USA. 2007;104(39):15484–9.

    PubMed  CAS  Google Scholar 

  61. Hebert SS, Horre K, Nicolai L, Bergmans B, Papadopoulou AS, Delacourte A, De Strooper B. MicroRNA regulation of Alzheimer’s Amyloid precursor protein expression. Neurobiol Dis. 2009;33(3):422–8.

    PubMed  CAS  Google Scholar 

  62. Trzaska KA, Reddy BY, Munoz JL, Li KY, Ye JH, Rameshwar P. Loss of RE-1 silencing factor in mesenchymal stem cell-derived dopamine progenitors induces functional maturity. Mol Cell Neurosci. 2008;39(2):285–90.

    PubMed  CAS  Google Scholar 

  63. Jing L, Jia Y, Lu J, Han R, Li J, Wang S, Peng T. MicroRNA-9 promotes differentiation of mouse bone mesenchymal stem cells into neurons by Notch signaling. Neuroreport. 2011;22(5):206–11.

    PubMed  CAS  Google Scholar 

  64. Chang SJ, Weng SL, Hsieh JY, Wang TY, Chang MD, Wang HW. MicroRNA-34a modulates genes involved in cellular motility and oxidative phosphorylation in neural precursors derived from human umbilical cord mesenchymal stem cells. BMC Med Genomics. 2011;4:65.

    PubMed  CAS  Google Scholar 

  65. Koh W, Sheng CT, Tan B, Lee QY, Kuznetsov V, Kiang LS, Tanavde V. Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha. BMC Genomics. 2010;11 Suppl 1:S6.

    PubMed  Google Scholar 

  66. Cui L, Zhou X, Li J, Wang L, Wang J, Li Q, Chu J, Zheng L, Wu Q, Han Z, Shi Y, Han Y, Fan D. Dynamic microRNA profiles of hepatic differentiated human umbilical cord lining-derived mesenchymal stem cells. PLoS One. 2012;7(9):e44737.

    PubMed  Google Scholar 

  67. Yu X, Cohen DM, Chen CS. miR-125b Is an adhesion-regulated microRNA that protects mesenchymal stem cells from anoikis. Stem Cells. 2012;30(5):956–64.

    PubMed  CAS  Google Scholar 

  68. Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ, Bellantuono I. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells. 2004;22(5):675–82.

    PubMed  CAS  Google Scholar 

  69. Nie Y, Han BM, Liu XB, Yang JJ, Wang F, Cong XF, Chen X. Identification of MicroRNAs involved in hypoxia- and serum deprivation-induced apoptosis in mesenchymal stem cells. Int J Biol Sci. 2011;7(6):762–8.

    PubMed  CAS  Google Scholar 

  70. Suzuki Y, Kim HW, Ashraf M, Haider H. Diazoxide potentiates mesenchymal stem cell survival via NF-kappaB-dependent miR-146a expression by targeting Fas. Am J Physiol Heart Circ Physiol. 2010;299(4):H1077–82.

    PubMed  CAS  Google Scholar 

  71. Wang J, Huang W, Wu Y, Hou J, Nie Y, Gu H, Li J, Hu S, Zhang H. MicroRNA-193 pro-proliferation effects for bone mesenchymal stem cells after low-level laser irradiation treatment through inhibitor of growth family, member 5. Stem Cells Dev. 2012;21(13):2508–19.

    PubMed  CAS  Google Scholar 

  72. Kim YJ, Hwang SH, Lee SY, Shin KK, Cho HH, Bae YC, Jung JS. miR-486-5p induces replicative senescence of human adipose tissue-derived mesenchymal stem cells and its expression is controlled by high glucose. Stem Cells Dev. 2012;21(10):1749–60.

    PubMed  CAS  Google Scholar 

  73. Stolzing A, Jones E, McGonagle D, Scutt A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 2008;129(3):163–73.

    PubMed  CAS  Google Scholar 

  74. Van Zant G, Liang Y. The role of stem cells in aging. Exp Hematol. 2003;31(8):659–72.

    PubMed  Google Scholar 

  75. Galderisi U, Helmbold H, Squillaro T, Alessio N, Komm N, Khadang B, Cipollaro M, Bohn W, Giordano A. In vitro senescence of rat mesenchymal stem cells is accompanied by downregulation of stemness-related and DNA damage repair genes. Stem Cells Dev. 2009;18(7):1033–42.

    PubMed  CAS  Google Scholar 

  76. Kretlow JD, Jin YQ, Liu W, Zhang WJ, Hong TH, Zhou G, Baggett LS, Mikos AG, Cao Y. Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells. BMC Cell Biol. 2008;9:60.

    PubMed  Google Scholar 

  77. Wagner W, Horn P, Castoldi M, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V, Ho AD. Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One. 2008;3(5):e2213.

    PubMed  Google Scholar 

  78. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, Croce CM. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA. 2007;104(40):15805–10.

    PubMed  CAS  Google Scholar 

  79. Yu JM, Wu X, Gimble JM, Guan X, Freitas MA, Bunnell BA. Age-related changes in mesenchymal stem cells derived from rhesus macaque bone marrow. Aging Cell. 2011;10(1):66–79.

    PubMed  CAS  Google Scholar 

  80. Pandey AC, Semon JA, Kaushal D, O’Sullivan RP, Glowacki J, Gimble JM, Bunnell BA. MicroRNA profiling reveals age-dependent differential expression of nuclear factor kappaB and mitogen-activated protein kinase in adipose and bone marrow-derived human mesenchymal stem cells. Stem Cell Res Ther. 2011;2(6):49.

    PubMed  CAS  Google Scholar 

  81. Bruno S, Grange C, Deregibus MC, Calogero RA, Saviozzi S, Collino F, Morando L, Busca A, Falda M, Bussolati B, Tetta C, Camussi G. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol. 2009;20(5):1053–67.

    PubMed  CAS  Google Scholar 

  82. Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, Tetta C, Camussi G. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One. 2010;5(7):e11803.

    PubMed  Google Scholar 

  83. Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int. 2010;78(9):838–48.

    PubMed  CAS  Google Scholar 

  84. Lotvall J, Valadi H. Cell to cell signalling via exosomes through esRNA. Cell Adh Migr. 2007;1(3):156–8.

    PubMed  Google Scholar 

  85. Chen TS, Lai RC, Lee MM, Choo AB, Lee CN, Lim SK. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res. 2010;38(1):215–24.

    PubMed  CAS  Google Scholar 

  86. Ryu CH, Park SA, Kim SM, Lim JY, Jeong CH, Jun JA, Oh JH, Park SH, Oh WI, Jeun SS. Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways. Biochem Biophys Res Commun. 2010;398(1):105–10.

    PubMed  CAS  Google Scholar 

  87. Cheng Z, Ou L, Zhou X, Li F, Jia X, Zhang Y, Liu X, Li Y, Ward CA, Melo LG, Kong D. Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther. 2008;16(3):571–9.

    PubMed  CAS  Google Scholar 

  88. Lu MH, Li CZ, Hu CJ, Fan YH, Wang SM, Wu YY, Liang GP, Yang SM. microRNA-27b suppresses mouse MSC migration to the liver by targeting SDF-1alphain vitro. Biochem Biophys Res Commun. 2012;421(2):389–95.

    PubMed  CAS  Google Scholar 

  89. Tome M, Lopez-Romero P, Albo C, Sepulveda JC, Fernandez-Gutierrez B, Dopazo A, Bernad A, Gonzalez MA. miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ. 2011;18(6):985–95.

    PubMed  CAS  Google Scholar 

  90. Wen Z, Zheng S, Zhou C, Yuan W, Wang J, Wang T. Bone marrow mesenchymal stem cells for post-myocardial infarction cardiac repair: microRNAs as novel regulators. J Cell Mol Med. 2012;16(4):657–71.

    PubMed  CAS  Google Scholar 

  91. Aguayo-Mazzucato C, Bonner-Weir S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol. 2010;6(3):139–48.

    PubMed  Google Scholar 

  92. Elnakish MT, Kuppusamy P, Khan M. Stem cell transplantation as a therapy for cardiac fibrosis. J Pathol. 2013;229(2):347–54.

    PubMed  CAS  Google Scholar 

  93. Tyagi AC, Sen U, Mishra PK. Synergy of microRNA and stem cell: a novel therapeutic approach for diabetes mellitus and cardiovascular diseases. Curr Diabetes Rev. 2011;7(6):367–76.

    PubMed  CAS  Google Scholar 

  94. Kim YJ, Hwang SH, Cho HH, Shin KK, Bae YC, Jung JS. MicroRNA 21 regulates the proliferation of human adipose tissue-derived mesenchymal stem cells and high-fat diet-induced obesity alters microRNA 21 expression in white adipose tissues. J Cell Physiol. 2012;227(1):183–93.

    PubMed  CAS  Google Scholar 

  95. Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini 3rd F. Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells. 2011;29(1):11–9.

    PubMed  CAS  Google Scholar 

  96. Bae S, Ahn JH, Park CW, Son HK, Kim KS, Lim NK, Jeon CJ, Kim H. Gene and microRNA expression signatures of human mesenchymal stromal cells in comparison to fibroblasts. Cell Tissue Res. 2009;335(3):565–73.

    PubMed  CAS  Google Scholar 

  97. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massague J. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451(7175):147–52.

    PubMed  CAS  Google Scholar 

  98. Hardy SA, Maltman DJ, Przyborski SA. Mesenchymal stem cells as mediators of neural differentiation. Curr Stem Cell Res Ther. 2008;3(1):43–52.

    PubMed  CAS  Google Scholar 

  99. Keilhoff G, Stang F, Goihl A, Wolf G, Fansa H. Transdifferentiated mesenchymal stem cells as alternative therapy in supporting nerve regeneration and myelination. Cell Mol Neurobiol. 2006;26(7–8):1235–52.

    PubMed  Google Scholar 

  100. Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA. 1999;96(19):10711–6.

    PubMed  CAS  Google Scholar 

  101. Lu P, Jones LL, Tuszynski MH. BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury. Exp Neurol. 2005;191(2):344–60.

    PubMed  CAS  Google Scholar 

  102. Liu Y, Jiang X, Zhang X, Chen R, Sun T, Fok KL, Dong J, Tsang LL, Yi S, Ruan Y, Guo J, Yu MK, Tian Y, Chung YW, Yang M, Xu W, Chung CM, Li T, Chan HC. Dedifferentiation-reprogrammed mesenchymal stem cells with improved therapeutic potential. Stem Cells. 2011;29(12):2077–89.

    PubMed  CAS  Google Scholar 

  103. Collino F, Bruno S, Deregibus MC, Tetta C, Camussi G. MicroRNAs and mesenchymal stem cells. Vitam Horm. 2011;87:291–320.

    PubMed  CAS  Google Scholar 

  104. Hu R, Li H, Liu W, Yang L, Tan YF, Luo XH. Targeting miRNAs in osteoblast differentiation and bone formation. Expert Opin Ther Targets. 2010;14(10):1109–20.

    PubMed  CAS  Google Scholar 

  105. Zou Z, Zhang Y, Hao L, Wang F, Liu D, Su Y, Sun H. More insight into mesenchymal stem cells and their effects inside the body. Expert Opin Biol Ther. 2010;10(2):215–30.

    PubMed  CAS  Google Scholar 

  106. Xu J, Wu W, Zhang L, Dorset-Martin W, Morris MW, Mitchell ME, Liechty KW. The role of MicroRNA-146a in the pathogenesis of the diabetic wound-healing impairment: correction with mesenchymal stem cell treatment. Diabetes. 2012;61(11):2906–12.

    PubMed  CAS  Google Scholar 

  107. Liu L, Wang Y, Fan H, Zhao X, Liu D, Hu Y, Kidd 3rd AR, Bao J, Hou Y. MicroRNA-181a regulates local immune balance by inhibiting proliferation and immunosuppressive properties of mesenchymal stem cells. Stem Cells. 2012;30(8):1756–70.

    PubMed  CAS  Google Scholar 

  108. Tran DH, Satou K, Ho TB. Finding microRNA regulatory modules in human genome using rule induction. BMC Bioinformatics. 2008;9 Suppl 12:S5.

    PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the grant support from AHA SDG (0930181N) to MK.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mahmood Khan Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Elnakish, M.T., Alhaider, I.A., Khan, M. (2013). MicroRNAs in Mesenchymal Stem Cells. In: Zhao, R. (eds) Essentials of Mesenchymal Stem Cell Biology and Its Clinical Translation. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6716-4_7

Download citation

Publish with us

Policies and ethics