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Published Online: 7 June 2010

Markers Distinguishing Mesenchymal Stem Cells from Fibroblasts Are Downregulated with Passaging

Publication: Stem Cells and Development
Volume 20, Issue Number 1

Abstract

Expansion of plastic-adherent bone marrow-derived mesenchymal stem cells (MSCs) results in gradual loss of osteogenic potential after passage 5–6. One explanation is contamination of MSC cultures with mature cells including fibroblasts. Identification and elimination of fibroblasts from MSC cultures could improve MSC yield and differentiation potential and also prevent tumor formation after MSC transplantation. However, no specific markers currently exist that can reliably discriminate between MSCs and fibroblasts. Flow cytometry analysis demonstrated that markers currently used to define MSCs, such as CD105, CD166, CD90, CD44, CD29, CD73, and CD9, are also expressed on human skin or lung fibroblasts. However, the level of expression of CD166 was significantly higher and that of CD9 was significantly lower in MSCs than in fibroblasts. CD146 was expressed only in MSCs. Using small focused microarrays, new markers differentially expressed in MSCs and fibroblasts were identified. Real-time polymerase chain reaction confirmed that expression of CD106, integrin alpha 11, and insulin-like growth factor-2 in MSCs was at least 10-fold higher than in fibroblasts; whereas expression of matrix metalloproteinase 1 and matrix metalloproteinase 3 was almost 100-fold lower. Flow cytometry and immunostaining demonstrated that CD106 protein expression on cell surface could be upregulated in MSCs but not in fibroblasts by the treatment with tumor necrosis factor-alpha. Comparison of surface expression of commonly used and newly identified MSC markers in MSCs cultures of passage 2 and passage 6 demonstrated that CD106 (with and without tumor necrosis factor-alpha treatment), integrin alpha 11, and CD146 were downregulated in MSCs of passage 6, and CD9 was upregulated; whereas all other markers did not change. Newly identified markers that have robust differences of expression in MSCs and fibroblasts on gene and protein level could be used for quality control of MSC cultures after expansion, cryopreservation, gene transfection, and other manipulations.

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References

1.
Izadpanah RD KaushaC KriedtF TsienB PatelJ DufourBA Bunnell2008. Long-term in vitro expansion alters the biology of adult mesenchymal stem cellsCancer Res684229-4238. 1. Izadpanah R, D Kausha, C Kriedt, F Tsien, B Patel, J Dufour and BA Bunnell. (2008). Long-term in vitro expansion alters the biology of adult mesenchymal stem cells. Cancer Res 68:4229–4238.
2.
Bonab MMK AlimoghaddamF TalebianSH GhaffariA GhavamzadehB Nikbin2006. Aging of mesenchymal stem cell in vitroBMC Cell Biol714. 2. Bonab MM, K Alimoghaddam, F Talebian, SH Ghaffari, A Ghavamzadeh and B Nikbin. (2006). Aging of mesenchymal stem cell in vitro. BMC Cell Biol 7:14.
3.
Rubio DJ Garcia-CastroMC MartinR de la FuenteJC CigudosaAC LloydA Bernad2005. Spontaneous human adult stem cell transformationCancer Res653035-3039. 3. Rubio D, J Garcia-Castro, MC Martin, R de la Fuente, JC Cigudosa, AC Lloyd and A Bernad. (2005). Spontaneous human adult stem cell transformation. Cancer Res 65:3035–3039.
4.
Miura MY MiuraHM Padilla-NashAA MolinoloB FuV PatelBM SeoW SonoyamaJJ ZhengCC BakerW ChenT RiedS Shi2006. Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformationStem Cells241095-1103. 4. Miura M, Y Miura, HM Padilla-Nash, AA Molinolo, B Fu, V Patel, BM Seo, W Sonoyama, JJ Zheng, CC Baker, W Chen, T Ried and S Shi. (2006). Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells 24:1095–1103.
5.
Zhou YFM Bosch-MarceH OkuyamaB KrishnamacharyH KimuraL ZhangDL HusoGL Semenza2006. Spontaneous transformation of cultured mouse bone marrow-derived stromal cellsCancer Res6610849-10854. 5. Zhou YF, M Bosch-Marce, H Okuyama, B Krishnamachary, H Kimura, L Zhang, DL Huso and GL Semenza. (2006). Spontaneous transformation of cultured mouse bone marrow-derived stromal cells. Cancer Res 66:10849–10854.
6.
Røsland GVA SvendsenA TorsvikE SobalaE McCormackH ImmervollJ MysliwietzJC TonnR GoldbrunnerPE LønningR BjerkvigC Schichor2009. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformationCancer Res695331-5339. 6. Røsland GV, A Svendsen, A Torsvik, E Sobala, E McCormack, H Immervoll, J Mysliwietz, JC Tonn, R Goldbrunner, PE Lønning, R Bjerkvig and C Schichor. (2009). Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res 69:5331–5339.
7.
Ratajczak MZM KuciaM MajkaR RecaJ Ratajczak2004. Heterogeneous populations of bone marrow stem cells—are we spotting on the same cells from the different angles?Folia Histochem Cytobiol42139-146. 7. Ratajczak MZ, M Kucia, M Majka, R Reca and J Ratajczak. (2004). Heterogeneous populations of bone marrow stem cells—are we spotting on the same cells from the different angles? Folia Histochem Cytobiol 42:139–146.
8.
Wagner WAD Ho2007. Mesenchymal stem cell preparations-comparing apples and orangesStem Cell Rev3239-248. 8. Wagner W and AD Ho. (2007). Mesenchymal stem cell preparations-comparing apples and oranges. Stem Cell Rev 3:239–248.
9.
Ho ADW WagnerW Franke2008. Heterogeneity of mesenchymal stromal cell preparationsCytotherapy10320-330. 9. Ho AD, W Wagner and W Franke. (2008). Heterogeneity of mesenchymal stromal cell preparations. Cytotherapy 10:320–330.
10.
Colter DCI SekiyaDJ Prockop2001. Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cellsProc Natl Acad Sci U S A987841-7845. 10. Colter DC, I Sekiya, and DJ Prockop. (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 U S A 98:7841–7845.
11.
Prockop DJSD Olson2007. Clinical trials with adult stem/progenitor cells for tissue repair: let's not overlook some essential precautionsBlood1093147-3151. 11. Prockop DJ and SD Olson. (2007). Clinical trials with adult stem/progenitor cells for tissue repair: let's not overlook some essential precautions. Blood 109:3147–3151.
12.
Colter DCR ClassCM DiGirolamoDJ Prockop2000. Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrowProc Natl Acad Sci U S A973213-3218. 12. Colter DC, R Class, CM DiGirolamo and DJ Prockop. (2000). Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. Proc Natl Acad Sci U S A 97:3213–3218.
13.
Johnstone BTM HeringAI CaplanVM GoldbergJU Yoo1998. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cellsExp Cell Res.238265-272. 13. Johnstone B, TM Hering, AI Caplan, VM Goldberg and JU Yoo. (1998). In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res.238:265–272.
14.
Pfaffla MW2001. A new mathematical model for relative quantification in real-time RT–PCRNucleic Acids Res29e45. 14. Pfaffla MW. (2001). A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res 29:e45.
15.
Livak KJTD Schmittgen2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) methodMethods25402-408. 15. Livak KJ and TD Schmittgen. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408.
16.
Leomil Coelho LFBE MotaPC SalesJT MarquesJG de OliveiraCA BonjardimPC Peregrino FerreiraEG Kroon2006. Integrin alpha 11 is a novel type I interferon stimulated geneCytokine33352-361. 16. Leomil Coelho LF, BE Mota, PC Sales, JT Marques, JG de Oliveira, CA Bonjardim, PC Peregrino Ferreira and EG Kroon. (2006). Integrin alpha 11 is a novel type I interferon stimulated gene. Cytokine 33:352–361.
17.
Sorrentino AM FerracinG CastelliM BiffoniG TomaselliM BaiocchiA FaticaM NegriniC PeschleM Valtieri2008. Isolation and characterization of CD146+ multipotent mesenchymal stromal cellsExp Hematol361035-1046. 17. Sorrentino A, M Ferracin, G Castelli, M Biffoni, G Tomaselli, M Baiocchi, A Fatica, M Negrini, C Peschle and M Valtieri. (2008). Isolation and characterization of CD146+ multipotent mesenchymal stromal cells. Exp Hematol 36:1035–1046.
18.
Horwitz EMK Le BlancM DominiciI MuellerI Slaper-CortenbachFC MariniRJ DeansDS KrauseA Keating2005. Clarification of the nomenclature for MSC The International Society for Cellular Therapy position statementCytotherapy7393-395. 18. Horwitz EM, K Le Blanc, M Dominici, I Mueller, I Slaper-Cortenbach, FC Marini, RJ Deans, DS Krause and A Keating. (2005). Clarification of the nomenclature for MSC. The International Society for Cellular Therapy position statement. Cytotherapy 7:393–395.
19.
Dominici MK Le BlancI MuellerI Slaper-CortenbachF MariniD KrauseR DeansA KeatingD ProckopE Horwitz2006. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statementCytotherapy8315-317. 19. Dominici M, K Le Blanc, I Mueller, I Slaper-Cortenbach, F Marini, D Krause, R Deans, A Keating, D Prockop and E Horwitz. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317.
20.
Ishii MC KoikeA IgarashiK YamanakaH PanY HigashiH KawaguchiM SugiyamaN KamataT IwataT MatsubaraK NakamuraH KuriharaK TsujiY Kato2005. Molecular markers distinguish bone marrow mesenchymal stem cells from fibroblastsBiochem Biophys Res Commun24297-303. 20. Ishii M, C Koike, A Igarashi, K Yamanaka, H Pan, Y Higashi, H Kawaguchi, M Sugiyama, N Kamata, T Iwata, T Matsubara, K Nakamura, H Kurihara, K Tsuji and Y Kato. (2005). Molecular markers distinguish bone marrow mesenchymal stem cells from fibroblasts. Biochem Biophys Res Commun 24:297–303.
21.
Bae SJH AhnCW ParkHK SonKS KimNK LimCJ JeonH Kim2009. Gene and microRNA expression signatures of human mesenchymal stromal cells in comparison to fibroblastsCell Tissue Res335565-573. 21. Bae S, JH Ahn, CW Park, HK Son, KS Kim, NK Lim, CJ Jeon and H Kim. (2009). Gene and microRNA expression signatures of human mesenchymal stromal cells in comparison to fibroblasts. Cell Tissue Res 335:565–573.
22.
Hee CKMA JonikasSB Nicoll2006. Influence of three-dimensional scaffold on the expression of osteogenic differentiation markers by human dermal fibroblastsBiomaterials27875-884. 22. Hee CK, MA Jonikas and SB Nicoll. (2006). Influence of three-dimensional scaffold on the expression of osteogenic differentiation markers by human dermal fibroblasts. Biomaterials 27:875–884.
23.
Lysy PAF SmetsC SibilleM NajimiEM Sokal2007. Human skin fibroblasts: from mesodermal to heptatocyte-like differentiationHepatol461574-1585. 23. Lysy PA, F Smets, C Sibille, M Najimi and EM Sokal. (2007). Human skin fibroblasts: from mesodermal to heptatocyte-like differentiation. Hepatol 46:1574–1585.
24.
Lorenz KM SickerE SchmelzerT RupfJ SalvetterM Schulz-SiegmundA Bader2008. Multilineage differentiation potential of human dermal skin-derived fibroblastsExp Dermatol11925-932. 24. Lorenz K, M Sicker, E Schmelzer, T Rupf, J Salvetter, M Schulz-Siegmund and A Bader. (2008). Multilineage differentiation potential of human dermal skin-derived fibroblasts. Exp Dermatol 11:925–932.
25.
Sommar PS PetterssonC NessH JohnsonG KratzJP Junker2010. Engineering three-dimensional cartilage- and bone-like tissues using human dermal fibroblasts and macroporous gelatine microcarriersJ Plast Reconstr Aesthet Surg631036-1046. 25. Sommar P, S Pettersson, C Ness, H Johnson, G Kratz and JP Junker. (2010). Engineering three-dimensional cartilage- and bone-like tissues using human dermal fibroblasts and macroporous gelatine microcarriers. J Plast Reconstr Aesthet Surg 63:1036–1046.
26.
Junker JPP SommarM SkogH JohnsonG Kratz2010. Adipogenic, chondrogenic and osteogenic differentiation of clonally derived human dermal fibroblastsCells Tissues Organs191105-118. 26. Junker JP, P Sommar, M Skog, H Johnson and G Kratz. (2010). Adipogenic, chondrogenic and osteogenic differentiation of clonally derived human dermal fibroblasts. Cells Tissues Organs 191:105–118.
27.
Karlsson LKJP JunkerM GrenegårdG Kratz2009. Human dermal fibroblasts: a potential cell source for endothelialization of vascular graftsAnn Vasc Surg23663-674. 27. Karlsson LK, JP Junker, M Grenegård and G Kratz. (2009). Human dermal fibroblasts: a potential cell source for endothelialization of vascular grafts. Ann Vasc Surg 23:663–674.
28.
Haniffa MAXN WangU HoltickM RaeJD IsaacsAM DickinsonCM HilkensMP Collin2007. Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cellsJ Immunol1791595-1604. 28. Haniffa MA, XN Wang, U Holtick, M Rae, JD Isaacs, AM Dickinson, CM Hilkens and MP Collin. (2007). Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. J Immunol 179:1595–1604.
29.
Haniffa MAMP CollinCD BuckleyF Dazzi2009. Mesenchymal stem cells: the fibroblasts' new clothes?Haematologica94258-263. 29. Haniffa MA, MP Collin, CD Buckley and F Dazzi. (2009). Mesenchymal stem cells: the fibroblasts' new clothes? Haematologica 94:258–263.
30.
Swart GW2002. Activated leukocyte cell adhesion molecule (CD166/ALCAM): developmental and mechanistic aspects of cell clustering and cell migrationEur J Cell Biol81313-321. 30. Swart GW. (2002). Activated leukocyte cell adhesion molecule (CD166/ALCAM): developmental and mechanistic aspects of cell clustering and cell migration. Eur J Cell Biol 81:313–321.
31.
Hemler ME2003. Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomainAnnu Rev Cell Dev Biol19397-422. 31. Hemler ME. (2003). Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 19:397–422.
32.
Morrish DWAR ShawJ SeehaferD BhardwajMT Paras1991. Preparation of fibroblast-free cytotrophoblast cultures utilizing differential expression of the CD9 antigenIn Vitro Cell Dev Biol27A303-306. 32. Morrish DW, AR Shaw, J Seehafer, D Bhardwaj and MT Paras. (1991). Preparation of fibroblast-free cytotrophoblast cultures utilizing differential expression of the CD9 antigen. In Vitro Cell Dev Biol 27A:303–306.
33.
Oritani KX WuK MedinaJ HudsonK MiyakeJM GimbleSA BursteinPW Kincade1996. Antibody ligation of CD9 modifies production of myeloid cells in long-term culturesBlood872252-2261. 33. Oritani K, X Wu, K Medina, J Hudson, K Miyake, JM Gimble, SA Burstein, and PW Kincade. (1996). Antibody ligation of CD9 modifies production of myeloid cells in long-term cultures. Blood 87:2252–2261.
34.
Aoyama KK OritaniT YokotaJ IshikawaT NishiuraK MiyakeY KanakuraY TomiyamaPW KincadeY Matsuzawa1999. Stromal cell CD9 regulates differentiation of hematopoietic stem/progenitor cellsBlood932586-2594. 34. Aoyama K, K Oritani, T Yokota, J Ishikawa, T Nishiura, K Miyake, Y Kanakura, Y Tomiyama, PW Kincade, and Y Matsuzawa. (1999). Stromal cell CD9 regulates differentiation of hematopoietic stem/progenitor cells. Blood 93:2586–2594.
35.
Whitham SEG MurphyP AngelHJ RahmsdorfBJ SmithA LyonsTJ HarrisJJ ReynoldsP HerrlichAJ Docherty1986. Comparison of human stromelysin and collagenase by cloning and sequence analysisBiochem J240913-916. 35. Whitham SE, G Murphy, P Angel, HJ Rahmsdorf, BJ Smith, A Lyons, TJ Harris, JJ Reynolds, P Herrlich and AJ Docherty. (1986). Comparison of human stromelysin and collagenase by cloning and sequence analysis. Biochem J 240:913–916.
36.
Formstone CJPJ ByrdHJ AmbroseJH RileyD HernandezCM McConvilleAM Taylor1993. The order and orientation of a cluster of metalloproteinase genes, stromelysin 2, collagenase, and stromelysin, together with D11S385, on chromosome 11q22-q23Genomics16289-291. 36. Formstone CJ, PJ Byrd, HJ Ambrose, JH Riley, D Hernandez, CM McConville and AM Taylor. (1993). The order and orientation of a cluster of metalloproteinase genes, stromelysin 2, collagenase, and stromelysin, together with D11S385, on chromosome 11q22-q23. Genomics 16:289–291.
37.
Saarialho-Kere UKAP PentlandH Birkedal-HansenWC ParksHG Welgus1994. Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic woundsJ Clin Invest9479-88. 37. Saarialho-Kere UK, AP Pentland, H Birkedal-Hansen, WC Parks and HG Welgus. (1994). Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds. J Clin Invest 94:79–88.
38.
Sellers AG Murphy1981. Collagenolytic enzymes and their naturally occurring inhibitorsInt Rev Connect Tissue Res9151-190. 38. Sellers A and G Murphy. (1981). Collagenolytic enzymes and their naturally occurring inhibitors. Int Rev Connect Tissue Res 9:151–190.
39.
Saus JS QuinonesY OtaniH NagaseED HarrisM Kurkinen1988. The complete primary structure of human matrix metalloproteinase-3. Identity with stromelysinJ Biol Chem156742-6745. 39. Saus J, S Quinones, Y Otani, H Nagase, ED Harris and M Kurkinen. (1988). The complete primary structure of human matrix metalloproteinase-3. Identity with stromelysin. J Biol Chem 15:6742–6745.
40.
Arakaki PAMR MarquesMC Santos2009. MMP-1 polymorphism and its relationship to pathological processesJ Biosci34313-320. 40. Arakaki PA, MR Marques and MC Santos. (2009). MMP-1 polymorphism and its relationship to pathological processes. J Biosci 34:313–320.
41.
Gullberg DT VellingG SjöbergT Sejersen1995. Up-regulation of a novel integrin alpha-chain (alpha mt) on human fetal myotubesDev Dyn20457-65. 41. Gullberg D, T Velling, G Sjöberg and T Sejersen. (1995). Up-regulation of a novel integrin alpha-chain (alpha mt) on human fetal myotubes. Dev Dyn 204:57–65.
42.
Velling TM Kusche-GullbergT SejersenD Gullberg1999. cDNA cloning and chromosomal localization of human alpha(11) integrin. A collagen-binding, I domain-containing, beta(1)-associated integrin alpha-chain present in muscle tissuesJ Biol Chem27425735-25742. 42. Velling T, M Kusche-Gullberg, T Sejersen and D Gullberg. (1999). cDNA cloning and chromosomal localization of human alpha(11) integrin. A collagen-binding, I domain-containing, beta(1)-associated integrin alpha-chain present in muscle tissues. J Biol Chem 274:25735–25742.
43.
Lehnert KJ NiE LeungSM GoughA WeaverWP YaoD LiuSX WangCM MorrisGW Krissansen1999. Cloning, sequence analysis, and chromosomal localization of the novel human integrin alpha11 subunit (ITGA11)Genomics60179-187. 43. Lehnert K, J Ni, E Leung, SM Gough, A Weaver, WP Yao, D Liu, SX Wang, CM Morris and GW Krissansen. (1999). Cloning, sequence analysis, and chromosomal localization of the novel human integrin alpha11 subunit (ITGA11). Genomics 60:179–187.
44.
Tiger CFF FougerousseG GrundströmT VellingD Gullberg2001. alpha11beta1 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cellsDev Biol237116-129. 44. Tiger CF, F Fougerousse, G Grundström, T Velling and D Gullberg. (2001). alpha11beta1 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cells. Dev Biol 237:116–129.
45.
Zhang WMJ KapylaJS PuranenCG KnightCF TigerOT PentikainenMS JohnsonRW FarndaleJ HeinoD Gullberg2003. alpha 11beta 1 integrin recognizes the GFOGER sequence in interstitial collagensJ Biol Chem2787270-7277. 45. Zhang WM, J Kapyla, JS Puranen, CG Knight, CF Tiger, OT Pentikainen, MS Johnson, RW Farndale, J Heino and D Gullberg. (2003). alpha 11beta 1 integrin recognizes the GFOGER sequence in interstitial collagens. J Biol Chem 278:7270–7277.
46.
Wang KKN LiuN RadulovichDA WigleMR JohnstonFA ShepherdMD MindenMS Tsao2002. Novel candidate tumor marker genes for lung adenocarcinomaOncogene217598-7604. 46. Wang KK, N Liu, N Radulovich, DA Wigle, MR Johnston, FA Shepherd, MD Minden and MS Tsao. (2002). Novel candidate tumor marker genes for lung adenocarcinoma. Oncogene 21:7598–7604.
47.
Zhu CQSN PopovaER BrownD Barsyte-LovejoyR NavabW ShihM LiM LuI JurisicaLZ PennD GullbergMS Tsao2007. Integrin alpha 11 regulates IGF-2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cellsProc Natl Acad Sci U S A10411754-11759. 47. Zhu CQ, SN Popova, ER Brown, D Barsyte-Lovejoy, R Navab, W Shih, M Li, M Lu, I Jurisica, LZ Penn, D Gullberg and MS Tsao. (2007). Integrin alpha 11 regulates IGF-2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cells. Proc Natl Acad Sci U S A 104:11754–11759.
48.
Wilson EMP Rotwein2006. Control of MyoD function during initiation of muscle differentiation by an autocrine signaling pathway activated by insulin-like growth factor-IIJ Biol Chem28129962-29971. 48. Wilson EM and P Rotwein. (2006). Control of MyoD function during initiation of muscle differentiation by an autocrine signaling pathway activated by insulin-like growth factor-II. J Biol Chem 281:29962–29971.
49.
Conover CA2008. Insulin-like growth factor-binding proteins and bone metabolismAm J Physiol Endocrinol Metab294E10-E14. 49. Conover CA. (2008). Insulin-like growth factor-binding proteins and bone metabolism. Am J Physiol Endocrinol Metab 294:E10–E14.
50.
Chao WPA D'Amore2008. IGF-2: epigenetic regulation and role in development and diseaseCytokine Growth Factor Rev19111-120. 50. Chao W and PA D'Amore. (2008). IGF-2: epigenetic regulation and role in development and disease. Cytokine Growth Factor Rev 19:111–120.
51.
Simmons PJB MasinovskyBM LongeneckerR BerensonB Torok-StorbWM Gallatin1992. Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cellsBlood80388-395. 51. Simmons PJ, B Masinovsky, BM Longenecker, R Berenson, B Torok-Storb, and WM Gallatin. (1992). Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood 80:388–395.
52.
Liu FY AkiyamaS TaiK MaruyamaY KawaguchiK MuramatsuKJ Yamaguchi2008. Changes in the expression of CD106, osteogenic genes, and transcription factors involved in the osteogenic differentiation of human bone marrow mesenchymal stem cellsBone Miner Metab26312-320. 52. Liu F, Y Akiyama, S Tai, K Maruyama, Y Kawaguchi, K Muramatsu and KJ Yamaguchi. (2008). Changes in the expression of CD106, osteogenic genes, and transcription factors involved in the osteogenic differentiation of human bone marrow mesenchymal stem cells. Bone Miner Metab 26:312–320.
53.
Böcker WD DochevaWC PrallV EgeaE PappouO RossmannC PopovW MutschlerC RiesM Schieker2008. IKK-2 is required for TNF-alpha-induced invasion and proliferation of human mesenchymal stem cellsJ Mol Med861183-1192. 53. Böcker W, D Docheva, WC Prall, V Egea, E Pappou, O Rossmann, C Popov, W Mutschler, C Ries, and M Schieker. (2008). IKK-2 is required for TNF-alpha-induced invasion and proliferation of human mesenchymal stem cells. J Mol Med 86:1183–1192.
54.
Fu XB HanS CaiY LeiT SunZ Sheng2009. Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-alpha and its possible role in wound healingWound Repair Regen17185-189. 54. Fu X, B Han, S Cai, Y Lei, T Sun, and Z Sheng. (2009). Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-alpha and its possible role in wound healing. Wound Repair Regen 17:185–189.
55.
Segers VFI Van RietLJ AndriesK LemmensMJ DemolderAJ De BeckerMM KockxGW De Keulenaer2006. Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanismsAm J Physiol Heart Circ Physiol290H1370-H1377. 55. Segers VF, I Van Riet, LJ Andries, K Lemmens, MJ Demolder, AJ De Becker, MM Kockx, and GW De Keulenaer. (2006). Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms. Am J Physiol Heart Circ Physiol 290:H1370–H1377.
56.
Smith ANE WillisVT ChanLA MuffleyFF IsikNS GibranAM Hocking2010. Mesenchymal stem cells induce dermal fibroblast responses to injuryExp Cell Res31648-54. 56. Smith AN, E Willis, VT Chan, LA Muffley, FF Isik, NS Gibran, and AM Hocking. (2010). Mesenchymal stem cells induce dermal fibroblast responses to injury. Exp Cell Res 316:48–54.
57.
Ren GX ZhaoL ZhangJ ZhangA L'HuillierW LingAI RobertsAD LeS ShiC ShaoY Shi2010. Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppressionJ Immunol1842321-2328. 57. Ren G, X Zhao, L Zhang, J Zhang, A L'Huillier, W Ling, AI Roberts, AD Le, S Shi, C Shao, and Y Shi. (2010). Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol 184:2321–2328.
58.
Miyazaki TY KitagawaK ToriyamaM KoboriS Torii2005. Isolation of two human fibroblastic cell populations with multiple but distinct potential of mesenchymal differentiation by ceiling culture of mature fat cells from subcutaneous adipose tissueDifferentiation7369-78. 58. Miyazaki T, Y Kitagawa, K Toriyama, M Kobori and S Torii. (2005). Isolation of two human fibroblastic cell populations with multiple but distinct potential of mesenchymal differentiation by ceiling culture of mature fat cells from subcutaneous adipose tissue. Differentiation 73:69–78.
59.
Gronthos SAC ZannettinoSJ HayS ShiSE GravesA KortesidisPJ Simmons2003. Molecular and cellular characterization of highly purified stromal stem cells derived from human bone marrowJ Cell Sci1161827-1835. 59. Gronthos S, AC Zannettino, SJ Hay, S Shi, SE Graves, A Kortesidis and PJ Simmons. (2003). Molecular and cellular characterization of highly purified stromal stem cells derived from human bone marrow. J Cell Sci 116:1827–1835.
60.
Gronthos SAC Zannettino2008. A method to isolate and purify human bone marrow stromal stem cellsMethods Mol Biol44945-57. 60. Gronthos S and AC Zannettino. (2008). A method to isolate and purify human bone marrow stromal stem cells. Methods Mol Biol 449:45–57.
61.
Fukiage KT AoyamaKR ShibataS OtsukaM FuruY KohnoK ItoY JinS FujitaS FujibayashiM NeoT NakayamaT NakamuraJ Toguchida2008. Expression of vascular cell adhesion molecule-1 indicates the differentiation potential of human bone marrow stromal cellsBiochem Biophys Res Commun365406-412. 61. Fukiage K, T Aoyama, KR Shibata, S Otsuka, M Furu, Y Kohno, K Ito, Y Jin, S Fujita, S Fujibayashi, M Neo, T Nakayama, T Nakamura and J Toguchida. (2008). Expression of vascular cell adhesion molecule-1 indicates the differentiation potential of human bone marrow stromal cells. Biochem Biophys Res Commun 365:406–412.
62.
Honczarenko MY LeM SwierkowskiI GhiranAM GlodekLE Silberstein2006. Human bone marrow stromal cells express a distinct set of biologically functional hemokine receptorsStem Cells241030-1041. 62. Honczarenko M, Y Le, M Swierkowski, I Ghiran, AM Glodek and LE Silberstein. (2006). Human bone marrow stromal cells express a distinct set of biologically functional hemokine receptors. Stem Cells 24:1030–1041.
63.
Majumdar MKM Keane-MooreD BuyanerWB HardyMA MoormanKR McIntoshJD Mosca2003. Characterization and functionality of cell surface molecules on human mesenchymal stem cellsJ Biomed Sci10228-241. 63. Majumdar MK, M Keane-Moore, D Buyaner, WB Hardy, MA Moorman, KR McIntosh and JD Mosca. (2003). Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 10:228–241.
64.
Schieker MC PautkeF HaastersJ SchiekerD DochevaW BöckerH GuelkanP NethM JochumW Mutschler2007. Human mesenchymal stem cells at the single-cell level: simultaneous seven-colour immunofluorescenceJ Anat210592-599. 64. Schieker M, C Pautke, F Haasters, J Schieker, D Docheva, W Böcker, H Guelkan, P Neth, M Jochum and W Mutschler. (2007). Human mesenchymal stem cells at the single-cell level: simultaneous seven-colour immunofluorescence. J Anat 210:592–599.
65.
Xu JW WangY KapilaJ LotzS Kapila2009. Multiple differentiation capacity of STRO-1+/CD146+PDL mesenchymal progenitor cellsStem Cells Dev18487-496. 65. Xu J, W Wang, Y Kapila, J Lotz and S Kapila. (2009). Multiple differentiation capacity of STRO-1+/CD146+PDL mesenchymal progenitor cells. Stem Cells Dev 18:487–496.
66.
Covas DTRA PanepucciAM FontesWA SilvaMD OrellanaMC FreitasL NederAR SantosLC PeresMC JamurMA Zago2008. Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblastsExp Hematol36642-654. 66. Covas DT, RA Panepucci, AM Fontes, WA Silva, MD Orellana, MC Freitas, L Neder, AR Santos, LC Peres, MC Jamur and MA Zago. (2008). Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts. Exp Hematol 36:642–654.
67.
Le Blanc KC TammikK RosendahlE ZetterbergO Ringdén2003. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cellsExp Hematol31890-896. 67. Le Blanc K, C Tammik, K Rosendahl, E Zetterberg, and O Ringdén. (2003). HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31:890–896.
68.
Mitchell JBK McIntoshS ZvonicS GarrettZE FloydA KlosterY Di HalvorsenRW StormsB GohG KilroyX WuJM Gimble2006. Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markersStem Cells24376-385. 68. Mitchell JB, K McIntosh, S Zvonic, S Garrett, ZE Floyd, A Kloster, Y Di Halvorsen, RW Storms, B Goh, G Kilroy, X Wu, and JM Gimble.(2006). Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells 24:376–385.
69.
Kern SH EichlerJ StoeveH KlüterK Bieback2006. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissueStem Cells241294-1301. 69. Kern S, H Eichler, J Stoeve, H Klüter, and K Bieback. (2006). Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301.

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cover image Stem Cells and Development
Stem Cells and Development
Volume 20Issue Number 1January 2011
Pages: 53 - 66
PubMed: 20528146

History

Published in print: January 2011
Published ahead of print: 26 October 2010
Published online: 7 June 2010
Accepted: 7 June 2010
Received: 5 February 2010

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Svetlana Halfon
*
Teva Pharmaceutical Industries, Rehovot, Israel.
Natalie Abramov*
Teva Pharmaceutical Industries, Rehovot, Israel.
Borislava Grinblat
Teva Pharmaceutical Industries, Rehovot, Israel.
Irene Ginis
Teva Pharmaceutical Industries, Rehovot, Israel.

Notes

Address correspondence to:Dr. Irene GinisMacrocure Ltd9 Bareket StreetPetach Tikva 49250Israel
E-mail: [email protected]

Author Disclosure Statement

No competing financial interests exist.

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