biostudies-literatureColletti EJNHLBI NIH HHS125-38https://www.ebi.ac.uk/biostudies/studies/S-EPMC3969729biostudies-literatureUnknown2(2)Human mesenchymal stem cells (MSC) hold great promise for cellular replacement therapies. Despite their contributing to phenotypically distinct cells in multiple tissues, controversy remains regarding whether the phenotype switch results from a true differentiation process. Here, we studied the events occurring during the first 120 h after human MSC transplantation into a large animal model. We demonstrate that MSC, shortly after engrafting different tissues, undergo proliferation and rapidly initiate the differentiative process, changing their phenotype into tissue-specific cells. Thus, the final level of tissue-specific cell contribution is not determined solely by the initial level of engraftment of the MSC within that organ, but rather by the proliferative capability of the ensuing tisStem cell researchGeneration of tissue-specific cells from MSC does not require fusion or donor-to-host mitochondrial/membrane transfer.PMC3969729R01 HL070566HL70566R01 HL073737HL73737Airey JAAlmeida-Porada GSimmons PJPorada CDZanjani EDColletti EJLiu WfalseGeneration of tissue-specific cells from MSC does not require fusion or donor-to-host mitochondrial/membrane transfer.Human mesenchymal stem cells (MSC) hold great promise for cellular replacement therapies. Despite their contributing to phenotypically distinct cells in multiple tissues, controversy remains regarding whether the phenotype switch results from a true differentiation process. Here, we studied the events occurring during the first 120 h after human MSC transplantation into a large animal model. We demonstrate that MSC, shortly after engrafting different tissues, undergo proliferation and rapidly initiate the differentiative process, changing their phenotype into tissue-specific cells. Thus, the final level of tissue-specific cell contribution is not determined solely by the initial level of engraftment of the MSC within that organ, but rather by the proliferative capability of the ensuing tis2009-01-01T00:00:00Z2009 Mar2025-04-18T12:46:16.396Z2019-03-27T01:24:11ZS-EPMC39697291938341810.1016/j.scr.2008.08.002