Fates of genetically engineered haematopoietic and mesenchymal stem cell grafts in normal and injured rat hearts.
There is an ongoing debate on the potential of adult stem cells as adjuvant therapy for patients with heart disease. The aim of our study was to evaluate the use of bone marrow (BM)-derived stem cells for cardiac cell and gene therapy in normal and ischaemia-injured rat hearts. Haematopoietic (HSCs) and mesenchymal stem cells (MSCs) were purified from the BM of adult rats and labelled by: (a) genetic transduction of the green fluorescent protein (GFP) using an oncoretroviral vector; (b) incorporation of the fluorescent dye PKH26 into the cell membrane; and (c) incorporation of bromodeoxyuridine into the chromosomal nucleic acid. Cells were directly injected into the beating heart (normal and shortly after coronary ligation). Retention of HSCs was--irrespective of the ischaemic injury--about 5% on day 3, and < 1% on days 10 and 28. Survival of MSCs was approximately 10-15% on day 3, but also < 5% at the later time points. Vector-mediated GFP expression was rapidly silenced after day 3. There was considerable tissue damage around the injection site. Transplanted cells did not migrate from the injection site. We did not observe phenotypical changes of the transplanted stem cells into cardiac or vascular cells.
Schierling
W
W
Department of Internal Medicine II, Regensburg University Medical Centre, Germany.
Kunz-Schughart
L A
LA
Muders
F
F
Riegger
G A J
GA
Griese
D P
DP
D000818:Animals; D015415:Biomarkers; D001853:Bone Marrow; D001973:Bromodeoxyuridine; D018929:Cell Culture Techniques; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D005818:Genetic Engineering; D006085:Graft Survival; D006331:Heart Diseases / Q000378:metabolism / Q000601:surgery; D006335:Heart Injuries / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009930:Organic Chemicals; D051381:Rats
D015415:Biomarkers; D009930:Organic Chemicals; C070080:PKH 26; D001973:Bromodeoxyuridine