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Cited by 440

The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.

Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function

Li, Wenzhong, Ma, Nan, Ong, Lee-Lee, Nesselmann, Catharina, Klopsch, Christian, Ladilov, Yury, Furlani, Dario, Piechaczek, Christoph, Moebius, Jeannette M., Lützow, Karola, Lendlein, Andreas, Stamm, Christof, Li, Ren-Ke, Steinhoff, Gustav·2007·Stem Cells
DOI 10.1634/stemcells.2006-0771
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Abstract

Engraftment of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for postinfarction left ventricular dysfunction. However, limited cell viability after transplantation into the myocardium has restricted its regenerative capacity. In this study, we genetically modified MSCs with an antiapoptotic Bcl-2 gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a rat left anterior descending ligation model via intracardiac injection. Rat MSCs were manipulated to overexpress the Bcl-2 gene. In vitro, the antiapoptotic and paracrine effects were assessed under hypoxic conditions. In vivo, the Bcl-2 gene-modified MSCs (Bcl-2-MSCs) were injected after myocardial infarction. The surviving cells were tracked after transplantation. Capillary density was quantified after 3 weeks. The left ventricular function was evaluated by pressure-volume loops. The Bcl-2 gene protected MSCs against apoptosis. In vitro, Bcl-2 overexpression reduced MSC apoptosis by 32% and enhanced vascular endothelial growth factor secretion by more than 60% under hypoxic conditions. Transplantation with Bcl-2-MSCs increased 2.2-fold, 1.9-fold, and 1.2-fold of the cellular survival at 4 days, 3 weeks, and 6 weeks, respectively, compared with the vector-MSC group. Capillary density in the infarct border zone was 15% higher in Bcl-2-MSC transplanted animals than in vector-MSC treated animals. Furthermore, Bcl-2-MSC transplanted animals had 17% smaller infarct size than vector-MSC treated animals and exhibited functional recovery remarkably. Our current findings support the premise that transplantation of antiapoptotic gene-modified MSCs may have values for mediating substantial functional recovery after acute myocardial infarction.

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Metadata

Authors
Li, W., Ma, N., Ong, L.-L., Nesselmann, C., Klopsch, C., Ladilov, Y., Furlani, D., Piechaczek, C., Moebius, J. M., Lützow, K., Lendlein, A., Stamm, C., Li, R.-K., & Steinhoff, G.
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2007-05-03
Volume
25
Issue
8
Pages
2118-2127
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
DOI
10.1634/stemcells.2006-0771
OpenAlex
W1969095342
Cited by
440
References
57
FWCI
16.36
Type
journal article
Language
en
Open access
closed

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