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UC-MSCs – A new Treatment Strategy for Chronic Myocardial Ischemia?

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Review of “\Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia” from Stem Cells Translational Medicine by Stuart P. Atkinson

Current knowledge on stem cell therapies for ischemic heart disease suggests that this strategy is potentially useful in the treatment of chronic stage [1]. However, less is understood about effects in acute ischemic heart disease. 

To this end, researchers from the laboratories of Xiao-Zhong Zhang and Shuang-Hong Lü (Affiliated Hospital of Academy of Military Medical Sciences, PR China) have recently assessed the impact of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) treatment in a large-animal model of chronic myocardial ischemia. Their data, reported in Stem Cells Translational Medicine, suggests that intracoronary stem cell delivery is safe and effective, and explore the potential for clinical translation of this new treatment strategy [2]. 

The study employed the pig as the large animal model and induced chronic myocardial ischemia using total left circumflex coronary artery (LCX) occlusion. Intracoronary UC-MSC transplantation took place at 4 weeks post occlusion, followed by intravenous delivery at 5 and 6 weeks, with final analysis at 8 weeks. Excitingly, transplantation of UC-MSCs mediated an alleviation in left ventricular remodeling and an improvement in systolic function. This also correlated with an increase in myocardial blood flow and the promotion of collateral arterial development. Further improvements included heightened angiogenesis, lowered myocardial apoptosis, and reduced fibrosis.

However, while some UC-MSCs had engrafted and a few expressed the endothelial marker vWF (See Figure - Engraftment of UC-MSCs [Red – left], Endothelial cells differentiation of the engrafted UC-MSCs [Green – Right]), the main regenerative function of UC-MSCs came via the enhancement of proangiogenic cytokine expression which can enhance neovascularization potential.

Overall, these exciting findings suggest the suitability of UC-MSCs as a new treatment strategy for chronic myocardial ischemia. The authors also note that the study employed widely available clinical-grade MSCs and commonly used delivery strategies that will hopefully facilitate future human clinical applications.

References

  • Assmus B, Leistner DM, Schachinger V, et al. Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival. Eur Heart J 2014;35:1275-1283.
  • Liu CB, Huang H, Sun P, et al. Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia. Stem Cells Transl Med 2016;5:1004-1013.