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Enhancing the Therapeutic Potential of Mesenchymal Stem Cells with the CRISPR-Cas System

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Abstract

Mesenchymal stem cells (MSCs), also known as multipotent mesenchymal stromal stem cells, are found in the perivascular space of several tissues. These cells have been subject of intense research in the last decade due to their low teratogenicity, as well as their ability to differentiate into mature cells and to secrete immunomodulatory and trophic factors. However, they usually promote only a modest benefit when transplanted in experimental disease models, one of the limitations for their clinical application. The CRISPR-Cas system, in turn, is highlighted as a simple and effective tool for genetic engineering. This system was tested in clinical trials over a relatively short period of time after establishing its applicability to the edition of the mammalian cell genome. Similar to the research evolution in MSCs, the CRISPR-Cas system demonstrated inconsistencies that limited its clinical application. In this review, we outline the evolution of MSC research and its applicability, and the progress of the CRISPR-Cas system from its discovery to the most recent clinical trials. We also propose perspectives on how the CRISPR-Cas system may improve the therapeutic potential of MSCs, making it more beneficial and long lasting.

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Funding

This work was supported by National Council for Scientific and Technological Development (CNPq, Brazil).

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Author notes

  1. Daniel Mendes Filho and Patrícia de Carvalho Ribeiro contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

    Daniel Mendes Filho & Ana Luiza Romero Terra dos Santos

  2. Laboratory of Immunology and Experimental Transplantation, São José do Rio Preto Medical School, São José do Rio Preto, São Paulo, Brazil

    Patrícia de Carvalho Ribeiro

  3. Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA

    Patrícia de Carvalho Ribeiro

  4. Department of Physiology, Biological and Natural Sciences Institute, Triangulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil

    Lucas Felipe Oliveira

  5. National Institute of Science and Technology for Regenerative Medicine (INCT-REGENERA-CNPq), Rio de Janeiro, RJ, Brazil

    Lucas Felipe Oliveira

  6. Minas Gerais Network for Tissue Engineering and Cell Therapy (REMETTECFAPEMIG), Belo Horizonte, MG, Brazil

    Lucas Felipe Oliveira

  7. Department of Pharmacology, Biological Sciences Institute, Goias Federal University, Goiania, Goias, Brazil

    Ricardo Cambraia Parreira & Mauro Cunha Xavier Pinto

  8. Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

    Rodrigo Ribeiro Resende

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  1. Daniel Mendes Filho
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  2. Patrícia de Carvalho Ribeiro
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  3. Lucas Felipe Oliveira
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  4. Ana Luiza Romero Terra dos Santos
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Correspondence to Ricardo Cambraia Parreira.

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Filho, D.M., de Carvalho Ribeiro, P., Oliveira, L.F. et al. Enhancing the Therapeutic Potential of Mesenchymal Stem Cells with the CRISPR-Cas System. Stem Cell Rev and Rep 15, 463–473 (2019). https://doi.org/10.1007/s12015-019-09897-0

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