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Patching up the Heart with Human Umbilical Cord Stem Cells

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Review of “Post-infarction Functional Recovery Driven by a Three-Dimensional Engineered Fibrin Patch Composed of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells” from Stem Cells Translational Medicine by Stuart P. Atkinson

The repair and regeneration of the damaged heart via the direct injection of cells with regenerative potential into the myocardium has met with some success but is generally limited by low cell survival. The construction of scaffolds or patches which combine cells with biological/synthetic materials and supporting factors has boosted cell survival [1, 2], but now researchers must tackle the problem of low angiogenesis and functional repair in the heart [3-5]. 

In a new study in Stem Cells Translational Medicine, researchers from the laboratory of Antoni Bayes-Genis (Hospital Universitari Germans Trias i Pujol, Barcelona) have assessed the potential of human umbilical cord blood multipotent mesenchymal stem cells (UCB-MSCs) within a three-dimensional (3D) engineered fibrin patch to induce vascular connections and improve cardiac function after myocardial infarction (MI) in mice [6].

The authors of the study first generated a homogenous culture of human UCB-MSCs expressing one fluorescent protein as a reporter of cell number and another reporter under the control of the CD31 promoter to assess vascular differentiation. After mixing with fibrin to form a biodegradable patch, the UCB-MSCs remained viable, with little cell death (Red in Figure A and A’) and with no CD31 expression (Absence of Red in Figure B), and so the authors then placed this fibrin-cell patch over the infarcted area of the myocardium in a mouse model of acute MI. Assessment of fluorescence suggested that MI-derived factors induced early proliferation and differentiation of UCB-MSCs within the patch, although at 3 weeks after implantation only an estimated 3% of cells remained viable.

Histological analysis found that patches adhered well to the mouse myocardium, and while no cells migrated into the myocardium, there was evidence of graft-derived CD31+ cells with an endothelial cell morphology which formed vessel-like structures within the patch itself. Morphometric analyses found no significant improvements in left ventricle scar thickness and volume, although the authors did see a significant improvement in cardiac function parameters (left ventricle ejection fraction (LVEF) and fractional shortening (FS)).

Overall, the engineered human UCB-MSCs-fibrin patch here described allows for improved cell viability and maintenance after transplant over a time period which allows for improved cardiac function following experimental MI. While the exact mechanisms which allowed for this improvement are not described, it is likely that the enhanced cell survival time allows for an extended paracrine effect through the release of cell protective factors. Therefore, the use of fibrin as a “glue” to fasten cells to the heart represents a viable option with advantages over other transplantation techniques, such as myocardial injection.

References

  1. Vunjak-Novakovic G, Lui KO, Tandon N, et al. Bioengineering heart muscle: a paradigm for regenerative medicine. Annu Rev Biomed Eng 2011;13:245-267.
  2. Galvez-Monton C, Prat-Vidal C, Roura S, et al. Update: Innovation in cardiology (IV). Cardiac tissue engineering and the bioartificial heart. Rev Esp Cardiol (Engl Ed) 2013;66:391-399.
  3. Drexler H and Hornig B Endothelial dysfunction in human disease. Journal of molecular and cellular cardiology 1999;31:51-60.
  4. Maulik N and Thirunavukkarasu M Growth factors and cell therapy in myocardial regeneration. Journal of molecular and cellular cardiology 2008;44:219-227.
  5. Roura S, Galvez-Monton C, and Bayes-Genis A The challenges for cardiac vascular precursor cell therapy: lessons from a very elusive precursor. J Vasc Res 2013;50:304-323.
  6. Roura S, Soler-Botija C, Bago JR, et al. Postinfarction Functional Recovery Driven by a Three-Dimensional Engineered Fibrin Patch Composed of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells. Stem Cells Transl Med 2015;4:956-966.