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Int. J. Mol. Sci. 2017, 18(10), 2087; doi:10.3390/ijms18102087

Challenges and Strategies for Improving the Regenerative Effects of Mesenchymal Stromal Cell-Based Therapies

1
Department of Research, Advanced Diagnostic, and Technological Innovation, Regina Elena National Cancer Institute, via E. Chianesi 53, Rome 00144, Italy
2
Stem Cells and Regenerative Medicine Laboratory, Foundation Institute of Pediatric Research “Città della Speranza”, corso Stati Uniti 4, Padova 35127, Italy
3
Department of Women’s and Children’s Health, University of Padova, Via Giustiniani 3, Padova 35128, Italy
*
Author to whom correspondence should be addressed.
Received: 31 August 2017 / Revised: 18 September 2017 / Accepted: 28 September 2017 / Published: 2 October 2017
(This article belongs to the Special Issue Stem Cell Research)
View Full-Text   |   Download PDF [641 KB, uploaded 2 October 2017]   |  

Abstract

Cell-based therapies have the potential to revolutionize current treatments for diseases with high prevalence and related economic and social burden. Unfortunately, clinical trials have made only modest improvements in restoring normal function to degenerating tissues. This limitation is due, at least in part, to the death of transplanted cells within a few hours after transplant due to a combination of mechanical, cellular, and host factors. In particular, mechanical stress during implantation, extracellular matrix loss upon delivery, nutrient and oxygen deprivation at the recipient site, and host inflammatory response are detrimental factors limiting long-term transplanted cell survival. The beneficial effect of cell therapy for regenerative medicine ultimately depends on the number of administered cells reaching the target tissue, their viability, and their promotion of tissue regeneration. Therefore, strategies aiming at improving viable cell engraftment are crucial for regenerative medicine. Here we review the major factors that hamper successful cell engraftment and the strategies that have been studied to enhance the beneficial effects of cell therapy. Moreover, we provide a perspective on whether mesenchymal stromal cell-derived extracellular vesicle delivery, as a cell-free regenerative approach, may circumvent current cell therapy limitations. View Full-Text
Keywords: anoikis; cell survival; cell therapy; cell transplantation; extracellular vesicles; hypoxia; mesenchymal stromal cells; regenerative medicine anoikis; cell survival; cell therapy; cell transplantation; extracellular vesicles; hypoxia; mesenchymal stromal cells; regenerative medicine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Baldari, S.; Di Rocco, G.; Piccoli, M.; Pozzobon, M.; Muraca, M.; Toietta, G. Challenges and Strategies for Improving the Regenerative Effects of Mesenchymal Stromal Cell-Based Therapies. Int. J. Mol. Sci. 2017, 18, 2087.

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