MSC Pretreatment for Improved Transplantation Viability Results in Improved Ventricular Function in Infarcted Hearts.

Mark F Pittenger,Saman Eghtesad,Pablo G Sanchez,Xiaoyan Liu,Bartley P Griffith,Ling Chen,Zhongjun Wu

doi:10.3390/ijms23020694

Mark F Pittenger, Saman Eghtesad + Show 5 more

Open Access

https://doi.org/10.3390/ijms23020694

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Abstract

Many clinical studies utilizing MSCs (mesenchymal stem cells, mesenchymal stromal cells, or multipotential stromal cells) are underway in multiple clinical settings; however, the ideal approach to prepare these cells in vitro and to deliver them to injury sites in vivo with maximal effectiveness remains a challenge. Here, pretreating MSCs with agents that block the apoptotic pathways were compared with untreated MSCs. The treatment effects were evaluated in the myocardial infarct setting following direct injection, and physiological parameters were examined at 4 weeks post-infarct in a rat permanent ligation model. The prosurvival treated MSCs were detected in the hearts in greater abundance at 1 week and 4 weeks than the untreated MSCs. The untreated MSCs improved ejection fraction in infarcted hearts from 61% to 77% and the prosurvival treated MSCs further improved ejection fraction to 83% of normal. The untreated MSCs improved fractional shortening in the infarcted heart from 52% to 68%, and the prosurvival treated MSCs further improved fractional shortening to 77% of normal. Further improvements in survival of the MSC dose seems possible. Thus, pretreating MSCs for improved in vivo survival has implications for MSC-based cardiac therapies and in other indications where improved cell survival may improve effectiveness.

Highlights

While it was once thought that the heart had no ability to repair or regenerate, studies have provided evidence of cardiomyocyte replacement in the normal heart as well as during post-injury remodeling that involve new cells migrating into the heart or provided from the cardiac tissue itself [1,2,3], and mouse cardiomyocytes are known to experience significant proliferation during adolescence [4,5]
The green fluorescent protein (GFP)-rat MSCs (rMSCs) used in these studies (Figure 1) were characterized by flow cytometry chondrocytes
GFP expressing rMSCs have notand been studied and for their newly ability to differentiate into adipocytes, osteoblasts, chondrocytes

Summary

Introduction

While it was once thought that the heart had no ability to repair or regenerate, studies have provided evidence of cardiomyocyte replacement in the normal heart as well as during post-injury remodeling that involve new cells migrating into the heart or provided from the cardiac tissue itself [1,2,3], and mouse cardiomyocytes are known to experience significant proliferation during adolescence [4,5]. Current strategies for cellular heart repair include identifying appropriate cell type(s); efficient delivery methods; local tissue conditions receptive to the cellular therapy (peri-infarct); improved engraftment; graft survival; and clinical translation and appropriate patient selection. A variety of stem/progenitor cells are under study that may have the appropriate characteristics to augment or replace cardiac cells lost following infarction. Such potential replacement cells include mesenchymal stem cells (MSCs) [7,8,9,10,11,12], c-kit+ cardiac progenitor cells [13,14,15], as well as embryonic stem cells (ESCs) [16,17,18,19,20] and induced pluripotent stem cells (iPSCs) [21,22,23,24,25,26,27]. The in vivo infarcted tissue is dramatically different from the in vitro culture environment used for cell expansion [30,31]

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