title: Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair.
abstract: Tissue regeneration from transplanted mesenchymal stromal cells (MSC) either through transdifferentiation or cell fusion was originally proposed as the principal mechanism underlying their therapeutic action. However, several studies have now shown that both these mechanisms are very inefficient. The low MSC engraftment rate documented in injured areas also refutes the hypothesis that MSC repair tissue damage by replacing cell loss with newly differentiated cells. Indeed, despite evidence of preferential homing of MSC to the site of myocardial ischemia, exogenously administered MSC show poor survival and do not persist in the infarcted area. Therefore, it has been proposed that the functional benefits observed after MSC transplantation in experimental models of tissue injury might be related to the secretion of soluble factors acting in a paracrine fashion. This hypothesis is supported by pre-clinical studies demonstrating equal or even improved organ function upon infusion of MSC-derived conditioned medium (MSC-CM) compared with MSC transplantation. Identifying key MSC-secreted factors and their functional role seems a reasonable approach for a rational design of nextgeneration MSC-based therapeutics. Here, we summarize the major findings regarding both different MSC-mediated paracrine actions and the identification of paracrine mediators.
authors.affiliation: Department of Molecular Medicine, Unit of Cardiology, University of Pavia, Pavia, Italy. m.gnecchi@unipv.it.|Department of Cardiothoracic and Vascular Sciences - Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. m.gnecchi@unipv.it.|Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. m.gnecchi@unipv.it.|Department of Medicine, University of Cape Town, Cape Town, South Africa. m.gnecchi@unipv.it.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gnecchi
authors.affiliation: Department of Molecular Medicine, Unit of Cardiology, University of Pavia, Pavia, Italy.|Department of Cardiothoracic and Vascular Sciences - Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Danieli
authors.affiliation: Department of Molecular Medicine, Unit of Cardiology, University of Pavia, Pavia, Italy.|Department of Cardiothoracic and Vascular Sciences - Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Malpasso
authors.affiliation: Department of Molecular Medicine, Unit of Cardiology, University of Pavia, Pavia, Italy.|Department of Cardiothoracic and Vascular Sciences - Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Ciuffreda
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D048091:Guided Tissue Regeneration; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019899:Paracrine Communication
keywords: Angiogenesis; Cell therapy; Conditioned medium; Cytoprotection; Mesenchymal stem cells; Paracrine mechanisms; Rigenerative medicine; Soluble factors; Tissue regeneration; Tissue repair