Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC

Ralf Hass, Cornelia Kasper, Stefanie Böhm, Roland Jacobs, Ralf Hass, Cornelia Kasper, Stefanie Böhm, Roland Jacobs

Abstract

The mesenchymal stroma harbors an important population of cells that possess stem cell-like characteristics including self renewal and differentiation capacities and can be derived from a variety of different sources. These multipotent mesenchymal stem cells (MSC) can be found in nearly all tissues and are mostly located in perivascular niches. MSC have migratory abilities and can secrete protective factors and act as a primary matrix for tissue regeneration during inflammation, tissue injuries and certain cancers.These functions underlie the important physiological roles of MSC and underscore a significant potential for the clinical use of distinct populations from the various tissues. MSC derived from different adult (adipose tissue, peripheral blood, bone marrow) and neonatal tissues (particular parts of the placenta and umbilical cord) are therefore compared in this mini-review with respect to their cell biological properties, surface marker expression and proliferative capacities. In addition, several MSC functions including in vitro and in vivo differentiation capacities within a variety of lineages and immune-modulatory properties are highlighted. Differences in the extracellular milieu such as the presence of interacting neighbouring cell populations, exposure to proteases or a hypoxic microenvironment contribute to functional developments within MSC populations originating from different tissues, and intracellular conditions such as the expression levels of certain micro RNAs can additionally balance MSC function and fate.

Figures

Figure 1
Figure 1
Major sources of human mesenchymal stem cells (MSC) . The sources can be distinguished between adult tissues, preferably bone marrow (BM), peripheral blood (PB) and adipose tissue (AT) and neonatal birth-associated tissues including placenta (PL), umbilical cord (UC) and cord blood (CB). Besides cord blood-derived mesenchymal stem cells (CB-MSC) other stem/progenitor cell populations from cord blood also include hematopoietic stem cells CB-HSC and two endothelial populations such as endothelial progenitor cells (EPC) and endothelial colony-forming cells (ECFC).
Figure 2
Figure 2
Senescence-associated β-galactosidase (SA-β-gal)-positive cells in the UC-derived mesenchymal stem cell culture under low (2%) serum concentration . Nuclei of senescent cells are surrounded by cyan dye. Moreover, serum deprivation is accompanied by a decrease of the proliferative potential in the cells and a significant increase in cell size.
Figure 3
Figure 3
MSC mediate immunosuppression of T and NK cells via different mechanisms . Soluble factors secreted by MSC such as iNOS, IDO, PGE2, sHLA-G5 can suppress T- and NK cell functions, whereas galectin-1 inhibits T cells but not NK cells. In addition, MSC can indirectly mediate immunosuppression by inhibiting dendritic cells and inducing the expansion of regulatory T cells (Tregs). Furthermore, MSC can directly interact with T and NK cells via cell to cell contact. However, receptors and ligands involved in the cell contact-dependent interaction mechanisms are still largely unknown.
Figure 4
Figure 4
Major characteristics of MSC and their functions in vitro and in vivo . MSC are involved in important pathways of cell renewal by mediating the regeneration of damaged or aging cells, supporting tissue repair at wound sites and modulating immune functions. Due to the migratory capabilities, MSC can interact with and support damaged normal tissue cells in the local vicinity by providing an appropriate microenvironment.

References

    1. Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976;4:267–274.
    1. Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. 2006;24:150–154. doi: 10.1016/j.tibtech.2006.01.010.
    1. Cao C, Dong Y. Study on culture and in vitro osteogenesis of blood-derived human mesenchymal stem cells. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2005;19:642–647.
    1. Griffiths MJ, Bonnet D, Janes SM. Stem cells of the alveolar epithelium. Lancet. 2005;366:249–260. doi: 10.1016/S0140-6736(05)66916-4.
    1. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–776. doi: 10.1016/S0092-8674(03)00687-1.
    1. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–147. doi: 10.1126/science.284.5411.143.
    1. Jörn W, Kuhbier BW, Radtke Christine, Peter M, Vogt, Kasper Cornelia, Reimers Kerstin. Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells. Adv Biochem Engin/Biotechnol. 2010;123:55–105. doi: 10.1007/10_2009_24.
    1. Kassis I, Zangi L, Rivkin R, Levdansky L, Samuel S, Marx G, Gorodetsky R. Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplant. 2006;37:967–976. doi: 10.1038/sj.bmt.1705358.
    1. Kitagawa YKM, Toriyama K, Kamei Y, Torii S. History of discovery of human adipose-derived stem cells and their clinical applications. Jpn J Plast Reconstr Surg. 2006;49:1097–1104.
    1. Wan C, He Q, Li G. Allogenic peripheral blood derived mesenchymal stem cells (MSCs) enhance bone regeneration in rabbit ulna critical-sized bone defect model. J Orthop Res. 2006;24:610–618. doi: 10.1002/jor.20119.
    1. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–317. doi: 10.1080/14653240600855905.
    1. Anzalone R, Lo Iacono M, Corrao S, Magno F, Loria T, Cappello F, Zummo G, Farina F, La Rocca G. New emerging potentials for human Wharton's jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity. Stem Cells Dev. 2010;19:423–438. doi: 10.1089/scd.2009.0299.
    1. Schaffler A, Buchler C. Concise review: adipose tissue-derived stromal cells--basic and clinical implications for novel cell-based therapies. Stem Cells. 2007;25:818–827. doi: 10.1634/stemcells.2006-0589.
    1. De Ugarte DA, Alfonso Z, Zuk PA, Elbarbary A, Zhu M, Ashjian P, Benhaim P, Hedrick MH, Fraser JK. Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow. Immunol Lett. 2003;89:267–270. doi: 10.1016/S0165-2478(03)00108-1.
    1. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13:4279–4295. doi: 10.1091/mbc.E02-02-0105.
    1. Tondreau T, Meuleman N, Delforge A, Dejeneffe M, Leroy R, Massy M, Mortier C, Bron D, Lagneaux L. Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity. Stem Cells. 2005;23:1105–1112. doi: 10.1634/stemcells.2004-0330.
    1. Barlow S, Brooke G, Chatterjee K, Price G, Pelekanos R, Rossetti T, Doody M, Venter D, Pain S, Gilshenan K, Atkinson K. Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells. Stem Cells Dev. 2008;17:1095–1107. doi: 10.1089/scd.2007.0154.
    1. In 't Anker PS, Scherjon SA, Kleijburg-van der Keur C, de Groot-Swings GM, Claas FH, Fibbe WE, Kanhai HH. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells. 2004;22:1338–1345. doi: 10.1634/stemcells.2004-0058.
    1. Brooke G, Tong H, Levesque JP, Atkinso K. Molecular trafficking mechanisms of multipotent mesenchymal stem cells derived from human bone marrow and placenta. Stem Cells Dev. 2008;17:929–940. doi: 10.1089/scd.2007.0156.
    1. Parolini O, Alviano F, Bagnara GP, Bilic G, Bühring HJ, Evangelista M, Hennerbichler S, Liu B, Magatti M, Mao N, Miki T, Marongiu F, Nakajima H, Nikaido T, Portmann-Lanz CB, Sankar V, Soncini M, Stadler G, Surbek D, Takahashi TA, Redl H, Sakuragawa N, Wolbank S, Zeisberger S, Zisch A, Strom SC. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells. 2008;26:300–311. doi: 10.1634/stemcells.2007-0594.
    1. Marcus AJ, Coyne TM, Rauch J, Woodbury D, Black IB. Isolation, characterization, and differentiation of stem cells derived from the rat amniotic membrane. Differentiation. 2008;76:130–144. doi: 10.1111/j.1432-0436.2007.00194.x.
    1. Miki T, Lehmann T, Cai H, Stolz DB, Strom SC. Stem cell characteristics of amniotic epithelial cells. Stem Cells. 2005;23:1549–1559. doi: 10.1634/stemcells.2004-0357.
    1. Tamagawa T, Oi S, Ishiwata I, Ishikawa H, Nakamura Y. Differentiation of mesenchymal cells derived from human amniotic membranes into hepatocyte-like cells in vitro. Hum Cell. 2007;20:77–84. doi: 10.1111/j.1749-0774.2007.00032.x.
    1. Wolbank S, van Griensven M, Grillari-Voglauer R, Peterbauer-Scherb A. Alternative sources of adult stem cells: human amniotic membrane. Adv Biochem Eng Biotechnol. 2010;123:1–27.
    1. Portmann-Lanz CB, Schoeberlein A, Huber A, Sager R, Malek A, Holzgreve W, Surbek DV. Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol. 2006;194:664–673. doi: 10.1016/j.ajog.2006.01.101.
    1. Soncini M, Vertua E, Gibelli L, Zorzi F, Denegri M, Albertini A, Wengler GS, Parolini O. Isolation and characterization of mesenchymal cells from human fetal membranes. J Tissue Eng Regen Med. 2007;1:296–305. doi: 10.1002/term.40.
    1. Chang CM, Kao CL, Chang YL, Yang MJ, Chen YC, Sung BL, Tsai TH, Chao KC, Chiou SH, Ku HH. Placenta-derived multipotent stem cells induced to differentiate into insulin-positive cells. Biochem Biophys Res Commun. 2007;357:414–420. doi: 10.1016/j.bbrc.2007.03.157.
    1. Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K. Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells. 2004;22:649–658. doi: 10.1634/stemcells.22-5-649.
    1. Igura K, Zhang X, Takahashi K, Mitsuru A, Yamaguchi S, Takashi TA. Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta. Cytotherapy. 2004;6:543–553. doi: 10.1080/14653240410005366-1.
    1. Okamoto K, Miyoshi S, Toyoda M, Hida N, Ikegami Y, Makino H, Nishiyama N, Tsuji H, Cui CH, Segawa K, Uyama T, Kami D, Miyado K, Asada H, Matsumoto K, Saito H, Yoshimura Y, Ogawa S, Aeba R, Yozu R, Umezawa A. Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells. Exp Cell Res. 2007;313:2550–2562. doi: 10.1016/j.yexcr.2007.04.028.
    1. Macias MI, Grande J, Moreno A, Domínguez I, Bornstein R, Flores AI. Isolation and characterization of true mesenchymal stem cells derived from human term decidua capable of multilineage differentiation into all 3 embryonic layers. Am J Obstet Gynecol. 2010;203:495.e9–495.e23. doi: 10.1016/j.ajog.2010.06.045.
    1. De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol. 2007;25:100–106. doi: 10.1038/nbt1274.
    1. Meng X, Ichim TE, Zhong J, Rogers A, Yin Z, Jackson J, Wang H, Ge W, Bogin V, Chan KW, Thébaud B, Riordan NH. Endometrial regenerative cells: a novel stem cell population. J Transl Med. 2007;5:57. doi: 10.1186/1479-5876-5-57.
    1. Majore I, Moretti P, Hass R, Kasper C. Identification of subpopulations in mesenchymal stem cell-like cultures from human umbilical cord. Cell Communication and Signaling. 2009;7:6. doi: 10.1186/1478-811X-7-S1-A6.
    1. Can A, Karahuseyinoglu S. Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells. 2007;25:2886–2895. doi: 10.1634/stemcells.2007-0417.
    1. Ennis J, Sarugaser R, Gomez A, Baksh D, Davies JE. Isolation, characterization, and differentiation of human umbilical cord perivascular cells (HUCPVCs) Methods Cell Biol. 2008;86:121–136.
    1. Majore I, Moretti P, Stahl F, Hass R, Kasper C. Growth and differentiation properties of mesenchymal stromal cell populations derived from whole human umbilical cord. Stem Cell Rev Rep. 2011;7:17–31. doi: 10.1007/s12015-010-9165-y.
    1. Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DO, Tukun A, Uckan D, Can A. Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells. 2007;25:319–331. doi: 10.1634/stemcells.2006-0286.
    1. Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 2005;23:220–229. doi: 10.1634/stemcells.2004-0166.
    1. Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC. Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells. 2004;22:1330–1337. doi: 10.1634/stemcells.2004-0013.
    1. Broxmeyer HE, Srour E, Orschell C, Ingram DA, Cooper S, Plett PA, Mead LE, Yoder MC. Cord blood stem and progenitor cells. Methods Enzymol. 2006;419:439–473.
    1. McNiece IK, Almeida-Porada G, Shpall EJ, Zanjani E. Ex vivo expanded cord blood cells provide rapid engraftment in fetal sheep but lack long-term engrafting potential. Exp Hematol. 2002;30:612–616. doi: 10.1016/S0301-472X(02)00805-6.
    1. Angelucci S, Marchisio M, Di Giuseppe F, Pierdomenico L, Sulpizio M, Eleuterio E, Lanuti P, Sabatino G, Miscia S, Di Ilio C. Proteome analysis of human Wharton's jelly cells during in vitro expansion. Proteome Sci. 2010;8:18. doi: 10.1186/1477-5956-8-18.
    1. Wang L, Ott L, Seshareddy K, Weiss ML, Detamore MS. Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells. Regen Med. 2011;6:95–109. doi: 10.2217/rme.10.98.
    1. Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med. 2004;8:301–316. doi: 10.1111/j.1582-4934.2004.tb00320.x.
    1. Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 2007;25:1384–1392. doi: 10.1634/stemcells.2006-0709.
    1. Wu LF, Wang NN, Liu YS, Wei X. Differentiation of Wharton's jelly primitive stromal cells into insulin-producing cells in comparison with bone marrow mesenchymal stem cells. Tissue Eng Part A. 2009;15:2865–2873. doi: 10.1089/ten.tea.2008.0579.
    1. Chen MY, Lie PC, Li ZL, Wei X. Endothelial differentiation of Wharton's jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells. Exp Hematol. 2009;37:629–640. doi: 10.1016/j.exphem.2009.02.003.
    1. Lu LL, Liu YJ, Yang SG, Zhao QJ, Wang X, Gong W, Han ZB, Xu ZS, Lu YX, Liu D, Chen ZZ, Han ZC. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica. 2006;91:1017–1026.
    1. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24:1294–1301. doi: 10.1634/stemcells.2005-0342.
    1. Peng L, Jia Z, Yin X, Zhang X, Liu Y, Chen P, Ma K, Zhou C. Comparative analysis of mesenchymal stem cells from bone marrow, cartilage, and adipose tissue. Stem Cells Dev. 2008;17:761–773. doi: 10.1089/scd.2007.0217.
    1. Shi YY, Nacamuli RP, Salim A, Longaker MT. The osteogenic potential of adipose-derived mesenchymal cells is maintained with aging. Plast Reconstr Surg. 2005;116:1686–1696. doi: 10.1097/01.prs.0000185606.03222.a9.
    1. Schipper BM, Marra KG, Zhang W, Donnenberg AD, Rubin JP. Regional anatomic and age effects on cell function of human adipose-derived stem cells. Ann Plast Surg. 2008;60:538–544. doi: 10.1097/SAP.0b013e3181723bbe.
    1. Van Harmelen V, Rohrig K, Hauner H. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects. Metabolism. 2004;53:632–637. doi: 10.1016/j.metabol.2003.11.012.
    1. La Rocca G, Anzalone R, Corrao S, Magno F, Loria T, Lo Iacono M, Di Stefano A, Giannuzzi P, Marasa L, Cappello F. et al.Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers. Histochem Cell Biol. 2009;131:267–282. doi: 10.1007/s00418-008-0519-3.
    1. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells. 2006;24:781–792. doi: 10.1634/stemcells.2005-0330.
    1. Conconi MT, Burra P, Di Liddo R, Calore C, Turetta M, Bellini S, Bo P, Nussdorfer GG, Parnigotto PP. CD105 (SH2)(+) cells from Wharton's jelly show in vitro and in vivo myogenic differentiative potential. Int J Mol Med. 2006;18:1089–1096.
    1. Mitchell KE, Weiss ML, Mitchell BM, Martin P, Davis D, Morales L, Helwig B, Beerenstrauch M, Abou-Easa K, Hildreth T, Troyer D, Medicetty S. Matrix cells from Wharton's jelly form neurons and glia. Stem Cells. 2003;21:50–60. doi: 10.1634/stemcells.21-1-50.
    1. Ohnishi S, Ohgushi H, Kitamura S, Nagaya N. Mesenchymal stem cells for the treatment of heart failure. Int J Hematol. 2007;86:17–21. doi: 10.1532/IJH97.07041.
    1. Fraser JK, Schreiber R, Strem B, Zhu M, Alfonso Z, Wulur I, Hedrick MH. Plasticity of human adipose stem cells toward endothelial cells and cardiomyocytes. Nat Clin Pract Cardiovasc Med. 2006;3(Suppl 1):S33–37.
    1. Fu YS, Shih YT, Cheng YC, Min MY. Transformation of human umbilical mesenchymal cells into neurons in vitro. J Biomed Sci. 2004;11:652–660. doi: 10.1007/BF02256131.
    1. Fu YS, Cheng YC, Lin MY, Cheng H, Chu PM, Chou SC, Shih YH, Ko MH, Sung MS. Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells. 2006;24:115–124. doi: 10.1634/stemcells.2005-0053.
    1. Lu LL, Song YP, Wei XD, Fang BJ, Zhang YL, Li YF. Comparative characterization of mesenchymal stem cells from human umbilical cord tissue and bone marrow. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16:140–146.
    1. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004;6:483–495. doi: 10.1016/S1534-5807(04)00075-9.
    1. Pairault J, Green H. A study of the adipose conversion of suspended 3T3 cells by using glycerophosphate dehydrogenase as differentiation marker. Proc Natl Acad Sci USA. 1979;76:5138–5142. doi: 10.1073/pnas.76.10.5138.
    1. Kakudo N, Shimotsuma A, Kusumoto K. Fibroblast growth factor-2 stimulates adipogenic differentiation of human adipose-derived stem cells. Biochem Biophys Res Commun. 2007;359:239–244. doi: 10.1016/j.bbrc.2007.05.070.
    1. Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998;47:507–514. doi: 10.2337/diabetes.47.4.507.
    1. Hong L, Colpan A, Peptan IA, Daw J, George A, Evans CA. 17-Beta estradiol enhances osteogenic and adipogenic differentiation of human adipose-derived stromal cells. Tissue Eng. 2007;13:1197–1203. doi: 10.1089/ten.2006.0317.
    1. Hou T, Xu J, Wu X, Xie Z, Luo F, Zhang Z, Zeng L. Umbilical Cord Wharton's Jelly: A New Potential Cell Source of Mesenchymal Stromal Cells for Bone Tissue Engineering. Tissue Eng Part A. 2009;15:2325–34. doi: 10.1089/ten.tea.2008.0402.
    1. Awad HA, Halvorsen YD, Gimble JM, Guilak F. Effects of transforming growth factor beta1 and dexamethasone on the growth and chondrogenic differentiation of adipose-derived stromal cells. Tissue Eng. 2003;9:1301–1312. doi: 10.1089/10763270360728215.
    1. Feng G, Wan Y, Balian G, Laurencin CT, Li X. Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells. Growth Factors. 2008;26:132–142. doi: 10.1080/08977190802105917.
    1. Chiou M, Xu Y, Longaker MT. Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells. Biochem Biophys Res Commun. 2006;343:644–652. doi: 10.1016/j.bbrc.2006.02.171.
    1. Estes BT, Wu AW, Storms RW, Guilak F. Extended passaging, but not aldehyde dehydrogenase activity, increases the chondrogenic potential of human adipose-derived adult stem cells. J Cell Physiol. 2006;209:987–995. doi: 10.1002/jcp.20808.
    1. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–228. doi: 10.1089/107632701300062859.
    1. Halvorsen YD, Franklin D, Bond AL, Hitt DC, Auchter C, Boskey AL, Paschalis EP, Wilkison WO, Gimble JM. Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. Tissue Eng. 2001;7:729–741. doi: 10.1089/107632701753337681.
    1. Malladi P, Xu Y, Yang GP, Longaker MT. Functions of vitamin D, retinoic acid, and dexamethasone in mouse adipose-derived mesenchymal cells. Tissue Eng. 2006;12:2031–2040. doi: 10.1089/ten.2006.12.2031.
    1. Arutyunyan IV, Rzhaninova AA, Volkov AV, Goldstein DV. Effect of dexamethasone on differentiation of multipotent stromal cells from human adipose tissue. Bull Exp Biol Med. 2009;147:503–508. doi: 10.1007/s10517-009-0548-5.
    1. Dragoo JL, Choi JY, Lieberman JR, Huang J, Zuk PA, Zhang J, Hedrick MH, Benhaim P. Bone induction by BMP-2 transduced stem cells derived from human fat. J Orthop Res. 2003;21:622–629. doi: 10.1016/S0736-0266(02)00238-3.
    1. Yang M, Ma QJ, Dang GT, Ma K, Chen P, Zhou CY. In vitro and in vivo induction of bone formation based on ex vivo gene therapy using rat adipose-derived adult stem cells expressing BMP-7. Cytotherapy. 2005;7:273–281. doi: 10.1080/14653240510027244.
    1. Bertram C, Hass R. Cellular responses to ROS-induced DNA damage and aging. Biol Chem. 2008;389:211–220. doi: 10.1515/BC.2008.031.
    1. Grayson WL, Zhao F, Bunnell B, Ma T. Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells. Biochem Biophys Res Comm. 2007;358:948–953. doi: 10.1016/j.bbrc.2007.05.054.
    1. Dos Santos F, Andrade PZ, Boura JS, Abecasis MM, da Silva CL, Cabral JM. Ex vivo expansion of human mesenchymal stem cells: a more effective cell proliferation kinetics and metabolism under hypoxia. J Cell Physiol. 2010;223:27–35.
    1. Wagner W, Ho AD, Zenke M. Different facets of aging in human mesenchymal stem cells. Tissue Eng Part B Rev. 2010;16:445–453. doi: 10.1089/ten.teb.2009.0825.
    1. Rosova I, Dao M, Capoccia B, Link D, Nolta JA. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells. 2008;26:2173–2182. doi: 10.1634/stemcells.2007-1104.
    1. Mohyeldin A, Garzón-Muvdi T, Quiñones-Hinojosa A. Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell. 2010;7:150–161. doi: 10.1016/j.stem.2010.07.007.
    1. Potier E, Ferreira E, Meunier A, Sedel L, Logeart-Avramoglou D, Petite H. Prolonged hypoxia concomitant with serum deprivation induces massive human mesenchymal stem cell death. Tissue Eng. 2007;13:1325–1331. doi: 10.1089/ten.2006.0325.
    1. Forsyth NR, Kay A, Hampson K, Downing A, Talbot R, McWhir J. Transcriptome alterations due to physiological normoxic (2% O2) culture of human embryonic stem cells. Regen Med. 2008;3:817–833. doi: 10.2217/17460751.3.6.817.
    1. Malladi P, Xu Y, Chiou M, Giaccia AJ, Longaker MT. Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells. Am J Physiol Cell Physiol. 2006;290:C1139–C1146.
    1. Markway BD, Tan GK, Brooke G, Hudson JE, Cooper-White JJ, Doran MR. Enhanced chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in low oxygen environment micropellet cultures. Cell Transplant. 2010;19:29–42. doi: 10.3727/096368909X478560.
    1. Lavrentieva A, Majore I, Kasper C, Hass R. Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells. Cell Communication and Signaling. 2010;8:18. doi: 10.1186/1478-811X-8-18.
    1. Das R, Jahr H, van Osch GJ, Farrell E. The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng Part B Rev. 2010;16:159–168. doi: 10.1089/ten.teb.2009.0296.
    1. Nagano M, Kimura K, Yamashita T, Ohneda K, Nozawa D, Hamada H, Yoshikawa H, Ochiai N, Ohneda O. Hypoxia responsive mesenchymal stem cells derived from human umbilical cord blood are effective for bone repair. Stem Cells Dev. 2010;19:1195–1210. doi: 10.1089/scd.2009.0447.
    1. Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E, Genrich K, Mehrotra S, Setty S, Smith B, Bartholomew A. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. European journal of immunology. 2008;38:1745–1755. doi: 10.1002/eji.200738129.
    1. Ge W, Jiang J, Baroja ML, Arp J, Zassoko R, Liu W, Bartholomew A, Garcia B, Wang H. Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2009;9:1760–1772.
    1. Casiraghi F, Azzollini N, Cassis P, Imberti B, Morigi M, Cugini D, Cavinato RA, Todeschini M, Solini S, Sonzogni A, Perico N, Remuzzi G, Noris M. Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells. Journal of immunology (Baltimore, Md: 1950) 2008;181:3933–3946.
    1. Popp FC, Eggenhofer E, Renner P, Slowik P, Lang SA, Kaspar H, Geissler EK, Piso P, Schlitt HJ, Dahlke MH. Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate. Transplant immunology. 2008;20:55–60. doi: 10.1016/j.trim.2008.08.004.
    1. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Experimental hematology. 2002;30:42–48. doi: 10.1016/S0301-472X(01)00769-X.
    1. Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439–141. doi: 10.1016/S0140-6736(04)16104-7.
    1. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O. Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371:1579–1586. doi: 10.1016/S0140-6736(08)60690-X.
    1. Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE. Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood. 2006;108:2114–2120. doi: 10.1182/blood-2005-11-011650.
    1. Ren G, Su J, Zhang L, Zhao X, Ling W, L'Huillie A, Zhang J, Lu Y, Roberts AI, Ji W, Zhang H, Rabson AB, Shi Y. Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem cells (Dayton, Ohio) 2009;27:1954–1962. doi: 10.1002/stem.118.
    1. Montesinos JJ, Flores-Figueroa E, Castillo-Medina S, Flores-Guzman P, Hernandez-Estevez E, Fajardo-Orduna G, Orozco S, Mayani H. Human mesenchymal stromal cells from adult and neonatal sources: comparative analysis of their morphology, immunophenotype, differentiation patterns and neural protein expression. Cytotherapy. 2009;11:163–176. doi: 10.1080/14653240802582075.
    1. Zeddou M, Briquet A, Relic B, Josse C, Malaise MG, Gothot A, Lechanteur C, Beguin Y. The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood. Cell biology international. 2010;34:693–701. doi: 10.1042/CBI20090414.
    1. Hatlapatka T, Moretti P, Lavrentieva A, Hass R, Marquardt N, Jacobs R, Kasper C. Optimization of Culture Conditions for the Expansion of Umbilical Cord-Derived Mesenchymal Stem or Stromal Cell-Like Cells Using Xeno-Free Culture Conditions. Tissue Eng Part C Methods. 2011;4:485–493.
    1. Moretti P, Hatlapatka T, Marten D, Lavrentieva A, Majore I, Hass R, Kasper C. Mesenchymal stromal cells derived from human umbilical cord tissues: primitive cells with potential for clinical and tissue engineering applications. Advances in Biochemical Engineering/Biotechnology. 2010;123:29–54.
    1. Casiraghi F, Noris M, Remuzzi G. Immunomodulatory effects of mesenchymal stromal cells in solid organ transplantation. Current opinion in organ transplantation. 2010. in press .
    1. Haynesworth SE, Baber MA, Caplan AI. Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. Journal of cellular physiology. 1996;166:585–592. doi: 10.1002/(SICI)1097-4652(199603)166:3<585::AID-JCP13>;2-6.
    1. Albini A, Melchiori A, Santi L, Liotta LA, Brown PD, Stetler-Stevenson WG. Tumor cell invasion inhibited by TIMP-2. Journal of the National Cancer Institute. 1991;83:775–779. doi: 10.1093/jnci/83.11.775.
    1. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838–3843. doi: 10.1182/blood.V99.10.3838.
    1. Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P. Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. Journal of immunology (Baltimore, Md: 1950) 2010;184:5885–5894.
    1. Lama VN, Smith L, Badri L, Flint A, Andrei AC, Murray S, Wang Z, Liao H, Toews GB, Krebsbach PH. et al.Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. The Journal of clinical investigation. 2007;117:989–996. doi: 10.1172/JCI29713.
    1. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell stem cell. 2008;2:141–150. doi: 10.1016/j.stem.2007.11.014.
    1. Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 2004;103:4619–4621. doi: 10.1182/blood-2003-11-3909.
    1. Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. The Journal of experimental medicine. 2002;196:459–468. doi: 10.1084/jem.20020121.
    1. Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood. 2008;111:1327–1333.
    1. Gieseke F, Bohringer J, Bussolari R, Dominici M, Handgretinger R, Muller I. Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cells. Blood. 2010;116:3770–3779. doi: 10.1182/blood-2010-02-270777.
    1. Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, Borg C, Saas P, Tiberghien P, Rouas-Freiss N, Carosella ED, Deschaseaux F. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem cells (Dayton, Ohio) 2008;26:212–222. doi: 10.1634/stemcells.2007-0554.
    1. Maccario R, Podesta M, Moretta A, Cometa A, Comoli P, Montagna D, Daudt L, Ibatici A, Piaggio G, Pozzi S, Frassoni F, Locatelli F. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica. 2005;90:516–525.
    1. Pevsner-Fischer M, Morad V, Cohen-Sfady M, Rousso-Noori L, Zanin-Zhorov A, Cohen S, Cohen IR, Zipori D. Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood. 2007;109:1422–1432. doi: 10.1182/blood-2006-06-028704.
    1. Liotta F, Angeli R, Cosmi L, Fili L, Manuelli C, Frosali F, Mazzinghi B, Maggi L, Pasini A, Lisi V, Santarlasci V, Consoloni L, Angelotti ML, Romagnani P, Parronchi P, Krampera M, Maggi E, Romagnani S, Annunziato F. Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling. Stem cells (Dayton, Ohio) 2008;26:279–289. doi: 10.1634/stemcells.2007-0454.
    1. Tomchuck SL, Zwezdaryk KJ, Coffelt SB, Waterman RS, Danka ES, Scandurro AB. Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem cells (Dayton, Ohio) 2008;26:99–107. doi: 10.1634/stemcells.2007-0563.
    1. Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSC, whereas MSC can inhibit IL-2-induced NK-cell proliferation. Blood. 2006;107:1484–1490. doi: 10.1182/blood-2005-07-2775.
    1. Shiroishi M, Tsumoto K, Amano K, Shirakihara Y, Colonna M, Braud VM, Allan DS, Makadzange A, Rowland-Jones S, Willcox B, Jones EY, van der Merwe PA, Kumagai I, Maenaka K. Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proceedings of the National Academy of Sciences of the United States of America. 2003;100:8856–8861. doi: 10.1073/pnas.1431057100.
    1. Favier B, Lemaoult J, Lesport E, Carosella ED. ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the late but not the early events of the NK-cell activating synapse. The FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2010;24:689–699.
    1. Huang XP, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel RD, Li RK. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation. 2010;122:2419–2429. doi: 10.1161/CIRCULATIONAHA.110.955971.
    1. Chan WK, Lau AS, Li JC, Law HK, Lau YL, Chan GC. MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-gamma challenge. Experimental hematology. 2008;36:1545–1555. doi: 10.1016/j.exphem.2008.06.008.
    1. Deuse T, Stubbendorff M, Tang-Quan K, Phillips N, Kay MA, Eiermann T, Phan TT, Volk HD, Reichenspurner H, Robbins RC, Schrepfer S. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplant. 2010. in press .
    1. Deng W, Han Q, Liao L, You S, Deng H, Zhao RC. Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol. 2005;24:458–463. doi: 10.1089/dna.2005.24.458.
    1. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M, Gualandi F, Mancardi GL, Pistoia V, Uccelli A. Blood. Vol. 107. United States; 2006. Human mesenchymal stem cells modulate B-cell functions; pp. 367–372.
    1. Rasmusson I, Le Blanc K, Sundberg B, Ringden O. Scand J Immunol. Vol. 65. England; 2007. Mesenchymal stem cells stimulate antibody secretion in human B cells; pp. 336–343.
    1. Traggiai E, Volpi S, Schena F, Gattorno M, Ferlito F, Moretta L, Martini A. Stem Cells. Vol. 26. United States; 2008. Bone marrow-derived mesenchymal stem cells induce both polyclonal expansion and differentiation of B cells isolated from healthy donors and systemic lupus erythematosus patients; pp. 562–569.
    1. Tomé M, López-Romero P, Albo C, Sepúlveda JC, Fernández-Gutiérrez B, Dopazo A, Bernad A, González MA. miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ. 2010. in press .
    1. Guo L, Zhao RC, Wu Y. The role of microRNAs in self-renewal and differentiation of mesenchymal stem cells. Exp Hematol. 2011. in press .
    1. Hass R. Rejuvenation in distinct cell populations - what does it mean? Exp Gerontol. 2009;44:634–638. doi: 10.1016/j.exger.2009.07.006.
    1. 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;38:215–224. doi: 10.1093/nar/gkp857.
    1. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massagué J. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451:147–152. doi: 10.1038/nature06487.
    1. Battula VL, Evans KW, Hollier BG, Shi Y, Marini FC, Ayyanan A, Wang RY, Brisken C, Guerra R, Andreeff M, Mani SA. Epithelial-Mesenchymal Transition-Derived Cells Exhibit Multi-Lineage Differentiation Potential Similar to Mesenchymal Stem Cells. Stem Cells. 2010;28:1435–1445. doi: 10.1002/stem.467.
    1. Hass R, Bertram C. Characterization of human breast cancer epithelial cells (HBCEC) derived from long term cultured biopsies. J Exp & Clin Cancer Res. 2009;28:127. doi: 10.1186/1756-9966-28-127.
    1. De Giorgi U, Cohen EN, Gao H, Mego M, Lee BN, Lodhi A, Cristofanilli M, Lucci A, Reuben JM. Mesenchymal stem cells expressing GD2 and CD271 correlate with breast cancer-initiating cells in bone marrow. Cancer Biol Ther. 2011. in press .
    1. Chaturvedi S, Hass R. Extracellular signals in young and aging breast epithelial cells and possible connections to age-associated breast cancer development. Mech Aging Dev. 2011. in press .
    1. Gruenloh W, Kambal A, Sondergaard C, McGee J, Nacey C, Kalomoiris S, Pepper K, Olson S, Fierro F, Nolta JA. Characterization and In Vivo Testing of Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells. Tissue Eng Part A. 2011. in press .
    1. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449:557–63. doi: 10.1038/nature06188.
    1. Hass R. Retrodifferentiation - a mechanism for cellular regeneration? Biol Chem. 2009;390:409–416. doi: 10.1515/BC.2009.050.

Source: PubMed

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