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Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
Human Neonatal Thymus Mesenchymal Stem Cells Promote Neovascularization and Cardiac Regeneration
Shuyun Wang1, Shan Huang1, Lianghui Gong1
1Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Insights
Neonatal thymus mesenchymal stem cells (ntMSCs) show promise for treating heart failure in congenital heart disease. These cells promote cardiac regeneration and protect heart tissue, offering a potential new therapy.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Therapy
Background:
- Congenital heart disease (CHD) poses a significant risk for heart failure in newborns.
- Limited treatment options exist for end-stage heart disease in pediatric patients.
- Neonatal thymus tissue, discarded during surgery, is a source of mesenchymal stem cells (MSCs).
Purpose of the Study:
- To evaluate the cardiac regenerative and protective potential of neonatal thymus-derived MSCs (ntMSCs).
- To compare ntMSCs with bone-derived MSCs regarding key regenerative factors.
Main Methods:
- In vitro assessment of ntMSC proangiogenic and regenerative factor secretion (Sonic Hedgehog - Shh).
- Organoid culture of ntMSCs to evaluate Shh expression.
- In vitro cytoprotective assays on neonatal rat cardiomyocytes.
- In vivo study using a rat model of myocardial infarction (left coronary ligation).
Main Results:
- ntMSCs expressed and secreted significantly more Shh than bone-derived MSCs.
- Organoid culture enhanced Shh expression in ntMSCs.
- ntMSCs demonstrated cytoprotective effects on cardiomyocytes against oxidative stress.
- In vivo, ntMSC cell sheets improved cardiac function, vascularization, and reduced scar size and cardiomyocyte death post-infarction.
Conclusions:
- Neonatal thymus MSCs possess significant cardiac regenerative properties.
- ntMSCs secrete proangiogenic factors like Shh, contributing to their therapeutic potential.
- These findings support further investigation of ntMSCs as a cell therapy for heart failure in CHD patients.
Abstract:
Newborns with critical congenital heart disease are at significant risk of developing heart failure later in life. Because treatment options for end-stage heart disease in children are limited, regenerative therapies for these patients would be of significant benefit. During neonatal cardiac surgery, a portion of the thymus is removed and discarded. This discarded thymus tissue is a good source of MSCs that we have previously shown to be proangiogenic and to promote cardiac function in an in vitro model of heart tissue. The purpose of this study was to further evaluate the cardiac regenerative and protective properties of neonatal thymus (nt) MSCs. We found that ntMSCs expressed and secreted the proangiogenic and cardiac regenerative morphogen sonic hedgehog (Shh) in vitro more than patient-matched bone-derived MSCs. We also found that organoid culture of ntMSCs stimulated Shh expression. We then determined that ntMSCs were cytoprotective of neonatal rat cardiomyocytes exposed to H2O2. Finally, in a rat left coronary ligation model, we found that scaffoldless cell sheet made of ntMSCs applied to the LV epicardium immediately after left coronary ligation improved LV function, increased vascular density, decreased scar size, and decreased cardiomyocyte death four weeks after infarction. We conclude that ntMSCs have cardiac regenerative properties and warrant further consideration as a cell therapy for congenital heart disease patients with heart failure.
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