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Mesenchymal Stem Cells pp 123–146Cite as

Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1416))

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.

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Acknowledgments

We acknowledge Laurene Kelly for expert editorial support. This work was supported by the Ministero Italiano della Sanità [Grant number GR-2008-1142781 and GR-2010-2320533], the Fondazione Cariplo [Grant number 2007-5984], and the Ministero Italiano degli Affari Esteri [Grant number ZA11GR2].

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Authors and Affiliations

  1. Department of Molecular Medicine, Unit of Cardiology, University of Pavia, Pavia, Italy

    Massimiliano Gnecchi M.D., Ph.D., F.E.S.C., Patrizia Danieli Ph.D., Giuseppe Malpasso Ph.D. & Maria Chiara Ciuffreda

  2. Department of Cardiothoracic and Vascular Sciences – Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Massimiliano Gnecchi M.D., Ph.D., F.E.S.C., Patrizia Danieli Ph.D., Giuseppe Malpasso Ph.D. & Maria Chiara Ciuffreda

  3. Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Massimiliano Gnecchi M.D., Ph.D., F.E.S.C., Patrizia Danieli Ph.D., Giuseppe Malpasso Ph.D. & Maria Chiara Ciuffreda

  4. Department of Medicine, University of Cape Town, Cape Town, South Africa

    Massimiliano Gnecchi M.D., Ph.D., F.E.S.C.

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  1. Massimiliano Gnecchi M.D., Ph.D., F.E.S.C.
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  2. Patrizia Danieli Ph.D.
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  3. Giuseppe Malpasso Ph.D.
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  4. Maria Chiara Ciuffreda
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Correspondence to Massimiliano Gnecchi M.D., Ph.D., F.E.S.C. .

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  1. Dept of Molecular Med,Unit of Cardiology, University of Pavia, PAVIA, Italy

    Massimiliano Gnecchi

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Gnecchi, M., Danieli, P., Malpasso, G., Ciuffreda, M.C. (2016). Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair. In: Gnecchi, M. (eds) Mesenchymal Stem Cells. Methods in Molecular Biology, vol 1416. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3584-0_7

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  • DOI: https://doi.org/10.1007/978-1-4939-3584-0_7

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