Genetically Engineered Mesenchymal Stem Cells Influence Gene
Expression in Donor Cardiomyocytes and the Recipient Heart
Mary Kearns-Jonker1,4*, Wangde Dai2, Mirja Gunthart1, Tania Fuentes4, Hsiao-Yun Yeh4, Paul Gerczuk2, Martin Pera3, Christine Mummery5 and Robert A Kloner2,3
1Dept of Cardiothoracic Surgery, Childrens Hospital Los Angeles, Los Angeles, CA, USA
2Heart Institute of Good Samaritan Hospital, Los Angeles, CA, USA
3Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern CA Keck School of Medicine, Los Angeles, CA, USA
4Dept of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA
5Dept of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands
- Corresponding Author:
- Mary Kearns-Jonker
Dept of Pathology and Human Anatomy
Loma Linda University School of Medicine
Loma Linda, CA, USA
E-mail: [email protected]
Received Date: April 30, 2012; Accepted Date: June 05, 2012; Published Date: June 07, 2012
Citation: Kearns-Jonker M, Dai W, Gunthart M, Fuentes T, Yeh HY, et al. (2012) Genetically Engineered Mesenchymal Stem Cells Influence Gene Expression in Donor Cardiomyocytes and the Recipient Heart. J Stem Cell Res Ther S1:005. doi:10.4172/2157-7633.S1-005
Copyright: © 2012 Kearns-Jonker M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Aims: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) or mesenchymal stem cells (MSCs) facilitate post-infarct recovery, but the potential benefit of combination therapy using MSCs and hESC-CMs has not been examined. Our objective was to define the gene expression changes in donor and host-derived cells that are induced in vivo after co-transplantation of cardiomyocytes with and without mesenchymal stem cells expressing the prosurvival gene heme oxygenase 1.
Methods and results: Human MSCs were engineered to over-express heme oxygenase-1 (HO-1) following lentiviral vector-mediated transduction. Athymic nude rats were subjected to myocardial infarction and received hESC-CMs alone, hESC-CMs plus human MSCs, hESC-CMs plus MSCs overexpressing HO-1, or saline. Real time PCR identified gene expression changes. Cardiac function was assessed by angiography. Co-transplantation of unmodified MSCs plus hESC-CMs elevated CXCR4, HGF, and IGF expression over levels induced by injection of hESC-derived cardiomyocytes alone. In animals co-transplanted with MSC over-expressing HO-1, the expression of these genes was further elevated. Gene expression levels of VEGF, TGF-β, CCL2, SMAD7, STAT3 and cardiomyocyte transcription factors were highest in the HO-1 MSC plus hESC-CM group at 30 days. Human CD31+, CD34+, isl-1+, NXK2.5 and c-kit+ transcripts were elevated. Rodent genes encoding NKX2.5, troponin T and CD31 were elevated and cell cycle genes were induced. Ejection fraction improved by six to seven percent.
Conclusions: Co-administration of HO-1 MSCs plus hESC-CMs increased expression of pro-survival and angiogenesis-promoting genes in human cells and transcripts of cardiac and endothelial cell markers in rodent cells, consistent with activation of tissue repair in both transplanted hESC-CMs and the host heart.