Survival and Development of Neonatal Rat Cardiomyocytes Transplanted into Adult Myocardium
Abstract
Transplantation of neonatal cardiomyocytes is a novel approach for the treatment of heart failure and myocardial infarction, but quantitative information on long-term cell survival and development is limited. Male donor cardiomyocytes were isolated from neonatal Fischer 344 rats (1-2 days), purified, and injected into the left ventricular wall of female syngeneic adult rats. One hour to 12 weeks later, genomic DNA was isolated from recipient hearts. The amount of male DNA per sample was determined by quantitative real-time TaqMan PCR of the male-specific Sry gene. Transplanted cell survival was 57 +/- 9% at 0-1 h, 24 +/- 6% at 24 h, 28 +/- 11% at 7 days, 27 +/- 3% at 14 days, 23 +/- 8% at 4 weeks and 15 +/- 3% at 12 weeks. The caspase inhibitor AcYVADcmk failed to improve transplanted cell survival at 24 h, suggesting that apoptosis did not play a major role in cell loss. Histology revealed that transplanted cells became more elongated over time, developed cross-striations, and that their nuclei increased in size. However, at 12 weeks, transplanted cells and their nuclei were still smaller than those of host myocardium. We established a quantitative survival profile for neonatal cardiomyocytes transplanted into normal adult myocardium. There was significant loss of cells within 24 h, but 15% of transplanted cells survived 12 weeks. Those cells that did survive underwent differentiation and developed visible sarcomeres, suggesting a potential contribution toward ventricular function.
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Studies show that 50-90% of injected cells are lost by extrusion and that ∼90% of remaining cells die within 1 wk of implantation.
“Studies show that 50–90% of injected cells are lost by extrusion (1) and that ∼90% of remaining cells die within 1 wk of implantation (2).”
From Proangiogenic scaffolds as functional templates for cardiac tissue engineering (2010) · cites this paper as [1]
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- Authors
- Müller-Ehmsen, J., Whittaker, P., Kloner, R. A., Dow, J. S., Sakoda, T., Long, T. I., Laird, P. W., & Kedes, L.
- Affiliations
- University of Southern California (US)
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 34
- Issue
- 2
- Pages
- 107-116
- ISSN
- 0022-2828 (ISSN-L)
- OpenAlex
- W2055162584
- Cited by
- 481
- References
- 16
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 14 · 2022: 12 · 2021: 14 · 2020: 8 · 2019: 12 · 2018: 14 · 2017: 24 · 2016: 18 · 2015: 22 · 2014: 20 · 2013: 30 · 2012: 42
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca075090-09, 5r01hl061488-05)
- National Heart, Lung, and Blood Institute (R01-HL61488-01, R01HL152771)
- National Cancer Institute (R01 CA75090)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cell survival, cardiomyocyte differentiation, SRY gene, apoptosis, caspase inhibitors, sarcomere development, heart failure, myocardial infarction, cell engraftment
- MeSH terms
- Age Factors, Animals, Base Sequence, Cell Differentiation, Cell Survival, Female, Graft Survival, Heart, Male, Molecular Sequence Data, Myocardium, Rats, Inbred F344, Stem Cells, Transplantation, Homologous, Signal Transduction, Heart Transplantation, Apoptosis, Stem Cell Transplantation, Rats
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