Early cell loss associated with mesenchymal stem cell cardiomyoplasty

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Maria C.,Moore,Joel L. Jr,Burrows,Brian J.,Kypson,Alan Collins (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Background: Human mesenchymal stem cells (hMSCs) show potential for therapeutic cellular cardiomyoplasty. However, a range of delivery methods, including direct intramyocardial injection, have resulted in poor engraftment in vivo. We used the in vivo rat heart model to study hMSC engraftment and retention in a normal beating heart. Materials and Methods: HMSCs transfected with green fluorescent protein were injected into the left ventricle (LV) of immunocompetent rats. Hearts were cryopreserved 30 minutes (Group A), 24 hours (Group B), and 5 days (Group C) post hMSC delivery. HMSC retention was estimated using confocal fluorescence microscopy and immunohistochemistry. Measured values were compared to projected GFP-positive cellular volumes. Immunohistochemical analyses probed for the presence of human cells with human prolyl hydroxylase beta (p4hβ) and an immune response with murine monocyte/macrophage antigen (CD68). Results: HMSC retention decreased significantly from 30 minutes to 5 days(p<0.05). In Group A the projected GFP positive cellular volume of 31% correlated with measured values and was significantly greater than the 1% predicted cellular volume in Group C. Moreover, human p4hβ was detected in Groups A and B, and not in Group C. Conversely, CD68 was detected in Groups B and C and not in Group A. Conclusions: In immunocompetent rats, engraftment and retention of hMSCs delivered intramyocardially significantly declines over a five day period. The influx of monocytes/macrophages suggests an unfavorable micro-environment for exogenous stem cell survival, confirmed by the absence of human cells detected five days post injection.

Additional Information

Publication

Other

Language: English

Date: 2012

Keywords

Mesenchymal stem cells, cardiomyoplasty, engraftment, intramyocardial injection, cardiac

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