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Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Both cultured and freshly isolated adipose tissue-derived stem cells enhance cardiac function after acute myocardial
Xiaowen Bai1, Yasheng Yan, Yao-Hua Song
1Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, SCRB2, Unit 951, 7435 Fannin Street, Houston, TX 77054, USA.
Insights
Freshly isolated adipose tissue-derived cells (fhADCs) and cultured adipose tissue-derived stem cells (hASCs) both improve cardiac function after myocardial infarction. These cells survive long-term, integrate into heart tissue, and promote myocardial repair.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Biology
Background:
- Myocardial infarction (MI) leads to significant cardiac damage and functional decline.
- Adipose tissue-derived cells offer potential for cardiac repair but require comparative analysis.
- Understanding cell survival, differentiation, and mechanisms is crucial for therapeutic development.
Purpose of the Study:
- To compare the efficacy of freshly isolated adipose tissue-derived cells (fhADCs) and cultured adipose tissue-derived stem cells (hASCs) in treating myocardial infarction.
- To evaluate the long-term survival and integration of these cells within the infarcted cardiac tissue.
- To elucidate whether observed therapeutic effects stem from direct cell differentiation or paracrine signaling.
Main Methods:
- Myocardial infarction was induced in immunodeficient mice.
- Mice received injections of fhADCs, hASCs, or a control solution in the peri-infarct region.
- Cardiac function, cell survival (bioluminescence imaging), differentiation (immunofluorescence), vascularization, and apoptosis were assessed.
Main Results:
- Both fhADCs and hASCs significantly improved cardiac function 4 weeks post-MI.
- Injected cells expressed cardiomyogenic markers (connexin 43, troponin I) and integrated into host tissue and vasculature.
- Cells survived up to 4 months, with increased vascular density and reduced apoptosis in treated hearts.
Conclusions:
- This study provides the first systematic comparison of fhADCs and hASCs for myocardial regeneration.
- Both fhADCs and hASCs demonstrate engraftment, long-term survival, and functional improvement in infarcted hearts.
- fhADCs represent a promising alternative cell source for myocardial repair, similar to hASCs.
Aims:
We assessed whether freshly isolated human adipose tissue-derived cells (fhADCs) or cultured human adipose tissue-derived stem cells (hASCs) have beneficial effects on cardiac function after myocardial infarction (MI), whether the injected cells can survive long term, and whether their effects result from direct differentiation or paracrine mechanisms.
Methods And Results:
Myocardial infarction was experimentally induced in severe combined immunodeficient mice, and either fhADCs, cultured hASCs, or phosphate-buffered saline was injected into the peri-infarct region. Myocardial function improved significantly in mice treated with hASCs or fhADCs 4 weeks after MI. Immunofluorescence revealed that grafted hASCs and fhADCs underwent cardiomyogenic differentiation pathway, as indicated by expression of connexin 43 and troponin I in a fusion-independent manner. Some of the injected cells integrated with host cardiomyocytes through connexin 43, and others were incorporated into newly formed vessels. Human adipose tissue-derived stem cells survived in injured hearts up to 4 months, as detected by luciferase-based bioluminescence imaging. Vascular density was significantly increased, and fewer apoptotic cells were present in the peri-infarct region of cell-injected mice.
Conclusion:
This is the first study to systematically compare the effects of fhADCs and hASCs on myocardial regeneration. Both cell types engraft into infarcted myocardium, survive, and improve myocardial function, suggesting that fhADCs, like hASCs, are a promising alternative cell source for myocardial repair after MI.
