The tissue microenvironment regulates such stem cell behaviors as self-renewal and differentiation. Attempts to mimic components of these microenvironments could provide new strategies for culturing and directing the behavior of stem cells. The aim of the present study was to mimic cardiac and umbilical cord tissue microenvironments in vitro and compare the resulting bone marrow-derived mesenchymal stem cell (BM-MSC) behaviors. We generated tissue microenvironments using conditioned medium (CM) and extracellular matrix (ECM) samples obtained from human heart and umbilical cord tissue explant cultures and by tissue decellularization. Mass spectrometry and immunostaining were used to characterize and determine the specific protein profiles of the ECMs and CMs. We demonstrated that the ECMs and CMs were not cytotoxic to BM-MSCs and could thus be tested via cell culture. The BM-MSCs showed a higher proliferation rate when cultured with umbilical cord-derived CM compared with the other analyzed conditions. Furthermore, the ECMs increased cell adhesion and migration. However, although the conditions tested in this work were able to maintain the viability and affect the proliferation, adhesion and migration of BM-MSCs in vitro, mimicking tissue microenvironments using ECM and CM was not sufficient to induce the cardiomyogenic differentiation of BM-MSCs. The present study provides a thorough characterization of the biological activity of these ECMs and CMs in human BM-MSC cultures.

1.
Bianco, P., P.G. Robey, P.J. Simmons (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2: 313-319.
2.
Celiz, A.D., J.G. Smith, R. Langer, D.G. Anderson, D.A. Winkler, D.A. Barrett, M.C. Davies, L.E. Young, C. Denning, M.R. Alexander (2014) Materials for stem cell factories of the future. Nat Mater 13: 570-579.
3.
Cox, J., M. Mann (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 26: 1367-1372.
4.
Cox, J., N. Neuhauser, A. Michalski, R.A. Scheltema, J.V. Olsen, M. Mann (2011) Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res 10: 1794-1805.
5.
Crapo, P.M., T.W. Gilbert, S.F. Badylak (2011) An overview of tissue and whole organ decellularization processes. Biomaterials 32: 3233-3243.
6.
Cuddihy, M.J., Y. Wang, C. Machi, J.H. Bahng, N.A. Kotov (2013) Replication of bone marrow differentiation niche: comparative evaluation of different three-dimensional matrices. Small 9: 1008-1015.
7.
de Castro Bras, L.E., T.A. Ramirez, K.Y. DeLeon-Pennell, Y.A. Chiao, Y. Ma, Q. Dai, G.V. Halade, K. Hakala, S.T. Weintraub, M.L. Lindsey (2013) Texas 3-step decellularization protocol: looking at the cardiac extracellular matrix. J Proteomics 86: 43-52.
8.
DeQuach, J.A., V. Mezzano, A. Miglani, S. Lange, G.M. Keller, F. Sheikh, K.L. Christman (2010) Simple and high yielding method for preparing tissue specific extracellular matrix coatings for cell culture. PLoS One 5: e13039.
9.
Dominici, M., K. Le Blanc, I. Mueller, I. Slaper-Cortenbach, F. Marini, D. Krause, R. Deans, A. Keating, D. Prockop, E. Horwitz (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8: 315-317.
10.
Eitan, Y., U. Sarig, N. Dahan, M. Machluf (2010) Acellular cardiac extracellular matrix as a scaffold for tissue engineering: in vitro cell support, remodeling, and biocompatibility. Tissue Eng Part C Methods 16: 671-683.
11.
Friedl, P., K. Wolf (2010) Plasticity of cell migration: a multiscale tuning model. J Cell Biol 188: 11-19.
12.
Li, L., T. Xie (2005) Stem cell niche: structure and function. Annu Rev Cell Dev Biol 21: 605-631.
13.
Lindner, U., J. Kramer, J. Behrends, B. Driller, N.O. Wendler, F. Boehrnsen, J. Rohwedel, P. Schlenke (2010) Improved proliferation and differentiation capacity of human mesenchymal stromal cells cultured with basement-membrane extracellular matrix proteins. Cytotherapy 12: 992-1005.
14.
Martin-Rendon, E., D. Sweeney, F. Lu, J. Girdlestone, C. Navarrete, S.M. Watt (2008) 5-azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies. Vox Sang 95: 137-148.
15.
Murphy, K.C., S.Y. Fang, J.K. Leach (2014) Human mesenchymal stem cell spheroids in fibrin hydrogels exhibit improved cell survival and potential for bone healing. Cell Tissue Res 357: 91-99.
16.
Pathan, M., S. Keerthikumar, C.S. Ang, L. Gangoda, C.Y. Quek, N.A. Williamson, D. Mouradov, O.M. Sieber, R.J. Simpson, A. Salim, A. Bacic, A.F. Hill, D.A. Stroud, M.T. Ryan, J.I. Agbinya, J.M. Mariadason, A.W. Burgess, S. Mathivanan (2015) FunRich: an open access standalone functional enrichment and interaction network analysis tool. Proteomics 15: 2597-2601.
17.
Rebelatto, C.K., A.M. Aguiar, M.P. Moretão, A.C. Senegaglia, P. Hansen, F. Barchiki, J. Oliveira, J. Martins, C. Kuligovski, F. Mansur, A. Christofis, V.F. Amaral, P.S. Brofman, S. Goldenberg, L.S. Nakao, A. Correa (2008) Dissimilar differentiation of mesenchymal stem cells from bone marrow, umbilical cord blood, and adipose tissue. Exp Biol Med (Maywood) 233: 901-913.
18.
Scanu, M., L. Mancuso, G. Cao (2011) Evaluation of the use of human mesenchymal stem cells for acute toxicity tests. Toxicol In Vitro 25: 1989-1995.
19.
Schittini, A.V., P.F. Celedon, M.A. Stimamiglio, M. Krieger, P. Hansen, F.D. da Costa, S. Goldenberg, B. Dallagiovanna, A. Correa (2010) Human cardiac explant-conditioned medium: soluble factors and cardiomyogenic effect on mesenchymal stem cells. Exp Biol Med (Maywood) 235: 1015-1024.
20.
Spradling, A., D. Drummond-Barbosa, T. Kai (2001) Stem cells find their niche. Nature 414: 98-104.
21.
Sreejit, P., R.S. Verma (2013) Natural ECM as biomaterial for scaffold based cardiac regeneration using adult bone marrow derived stem cells. Stem Cell Rev 9: 158-171.
22.
Veevers-Lowe, J., S.G. Ball, A. Shuttleworth, C.M. Kielty (2011) Mesenchymal stem cell migration is regulated by fibronectin through α5β1-integrin-mediated activation of PDGFR-β and potentiation of growth factor signals. J Cell Sci 124: 1288-1300.
23.
Wang, L., K. Hirayasu, M. Ishizawa, Y. Kobayashi (1994) Purification of genomic DNA from human whole blood by isopropanol-fractionation with concentrated Nal and SDS. Nucleic Acids Res 22: 1774-1775.
24.
Watt, F.M., W.T. Huck (2013) Role of the extracellular matrix in regulating stem cell fate. Nat Rev Mol Cell Biol 14: 467-473.
25.
Zhang, Y., Y. He, S. Bharadwaj, N. Hammam, K. Carnagey, R. Myers, A. Atala, M. van Dyke (2009) Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotype. Biomaterials 30: 4021-4028.
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