Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine.

Patricia Kauanna Fonseca Damasceno,Girlaine Café Santos,Massimo Dominici,Milena Botelho Pereira Soares,Iasmim Diniz Orge,Giulia Grisendi,Giulia Golinelli,Daniela Nascimento Silva,Ricardo Ribeiro Dos Santos,Massimo Pinelli,Thaís Alves De Santana,Juliana Fonseca Albuquerque

doi:10.3389/fcell.2020.00737

Abstract

Mesenchymal stem/stromal cells (MSCs) have been widely studied in the field of regenerative medicine for applications in the treatment of several disease settings. The therapeutic potential of MSCs has been evaluated in studies in vitro and in vivo, especially based on their anti-inflammatory and pro-regenerative action, through the secretion of soluble mediators. In many cases, however, insufficient engraftment and limited beneficial effects of MSCs indicate the need of approaches to enhance their survival, migration and therapeutic potential. Genetic engineering emerges as a means to induce the expression of different proteins and soluble factors with a wide range of applications, such as growth factors, cytokines, chemokines, transcription factors, enzymes and microRNAs. Distinct strategies have been applied to induce genetic modifications with the goal to enhance the potential of MCSs. This review aims to contribute to the update of the different genetically engineered tools employed for MSCs modification, as well as the factors investigated in different fields in which genetically engineered MSCs have been tested.

Highlights

In the field of stem cell therapy, mesenchymal stem/stromal cells (MSCs) have been widely used in a large number of in vitro and in vivo studies, as well as in approximately 1000 clinical trials
Some studies have shown that transplanted Mesenchymal stem/stromal cells (MSCs) presented a poor survival rate and proliferation (Shi and Li, 2008; Park J.S. et al, 2015; Li et al, 2016; Silva et al, 2018c; Zhao et al, 2019), possibly due to the hostile microenvironment of lesioned tissues, which could lead to nutrient deprivation and cell death (Moya et al, 2018)
Confirmation of the efficacy of MSC-TNF-related apoptosis-inducing ligand (TRAIL) in vivo were shown by Spano et al (2019), which tested Ad-MSC-TRAIL in pancreatic cancer, finding a 37% reduction in tumor size in Ad-MSC-TRAIL group compared to non-modified Ad-MSCs, a result which was similar to the that found in the group treated with recombinant TRAIL

Summary

Introduction

In the field of stem cell therapy, mesenchymal stem/stromal cells (MSCs) have been widely used in a large number of in vitro and in vivo studies, as well as in approximately 1000 clinical trials. These are multipotent stem cells that must meet minimum criteria, such as plastic adherence, expression of specific surface markers and the ability to differentiate in adipocytes, chondrocytes and osteocytes (Dominici et al, 2006). Approaches aiming to enhance the efficacy of MSC transplantation are needed in order to achieve the suitable results

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