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Updated: May 3, 2026
In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Human cardiosphere-derived cells from advanced heart failure patients exhibit augmented functional potency in
Ke Cheng1, Konstantinos Malliaras1, Rachel Ruckdeschel Smith1,2
1Cedars-Sinai Heart Institute, Los Angeles, California.
Insights
Cardiosphere-derived cells (CDCs) from advanced heart failure patients show enhanced regenerative capacity after myocardial infarction (MI). These cells, possibly via SDF-1, improve heart function and reduce scar tissue more effectively than those from healthy or recently infarcted hearts.
Area of Science:
- Cardiology
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Pre-clinical studies and the CADUCEUS trial suggest cardiosphere-derived cells (CDCs) from healthy or recently infarcted hearts can regenerate cardiac tissue post-myocardial infarction (MI).
- The regenerative potential of CDCs from patients with advanced heart failure (HF) remains unexplored.
Purpose of the Study:
- To compare the regenerative potency and functional benefits of CDCs derived from non-failing (NF), MI, and advanced HF human hearts in a mouse model of acute MI.
Main Methods:
- CDCs were isolated from three donor groups: NF, MI (9-35 days post-MI), and HF (advanced cardiomyopathy).
- The regenerative potential and functional benefits of these CDCs were assessed in a mouse model of acute MI.
Main Results:
- Cell growth and phenotype were consistent across all groups.
- CDCs from advanced HF patients demonstrated the greatest therapeutic benefit in mice, significantly improving left ventricular ejection fraction and reducing infarct scar.
- HF CDCs secreted higher levels of SDF-1, correlating with enhanced angiogenesis, myocyte survival, and better engraftment, while also recruiting endogenous stem cells.
Conclusions:
- CDCs from advanced HF patients possess augmented potency in improving ventricular function post-MI.
- SDF-1-mediated mechanisms are likely involved in the enhanced regenerative capacity of HF CDCs.
Objectives:
This study sought to compare the regenerative potency of cells derived from healthy and diseased human hearts.
Background:
Results from pre-clinical studies and the CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial support the notion that cardiosphere-derived cells (CDCs) from normal and recently infarcted hearts are capable of regenerating healthy heart tissue after myocardial infarction (MI). It is unknown whether CDCs derived from advanced heart failure (HF) patients retain the same regenerative potency.
Methods:
In a mouse model of acute MI, we compared the regenerative potential and functional benefits of CDCs derived from 3 groups: 1) non-failing (NF) donor: healthy donor hearts post-transplantation; 2) MI: patients who had an MI 9 to 35 days before biopsy; and 3) HF: advanced cardiomyopathy tissue explanted at cardiac transplantation.
Results:
Cell growth and phenotype were identical in all 3 groups. Injection of HF CDCs led to the greatest therapeutic benefit in mice, with the highest left ventricular ejection fraction, thickest infarct wall, most viable tissue, and least scar 3 weeks after treatment. In vitro assays revealed that HF CDCs secreted higher levels of stromal cell-derived factor (SDF)-1, which may contribute to the cells' augmented resistance to oxidative stress, enhanced angiogenesis, and improved myocyte survival. Histological analysis indicated that HF CDCs engrafted better, recruited more endogenous stem cells, and induced greater angiogenesis and cardiomyocyte cell-cycle re-entry. CDC-secreted SDF-1 levels correlated with decreases in scar mass over time in CADUCEUS patients treated with autologous CDCs.
Conclusions:
CDCs from advanced HF patients exhibit augmented potency in ameliorating ventricular dysfunction post-MI, possibly through SDF-1–mediated mechanisms.
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