A tissue engineered approach to progenitor cell delivery and myocardial repair

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Simpson, David Lemar
Dudley, Samuel C., Jr.
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Heart failure accounts for more deaths in the United States than any other pathology. Unfortunately, repairing the heart after pathological injury has become an overwhelming task for physicians and researchers to overcome. Fortunately, cellular cardiomyoplasty has emerged as a promising solution for sufferers of heart failure. Such a therapy is limited in efficacy due to poor engraftment efficiencies, however. To address this issue, we have developed a tissue engineered vehicle for cell delivery. Use of a "cardiac patch" resulted in localized and efficient delivery of human mesenchymal stem cells (hMSC) to infarcted myocardium. Application of a cardiac patch also attenuated adverse remodeling. Additionally, the culture of stem/progenitor cells within three dimensional collagen constructs led to modulations in cell function, which did not promote enhanced angiogenesis in vitro or in vivo. Despite enhanced neovessel formation, hMSC patches were more beneficial at augmenting myocardial repair compared to directly injected hMSC. Lastly, although hMSC represent an effective cell source option for enhancing cardiac repair they require additional purification and expansion steps which inherently delay the turnover before treatment. Therefore, suitable cell alternative are being sought. Human embryonic stem cell derived mesenchymal (B4) cells display several phenotypic similarities to hMSC. B4 progenitor cells responded similarly to hMSC in 3D culture. In addition B4 progenitor cell patch application to infarcted myocardium resulted in similar indices of repair compared to hMSC. Thus, a tissue engineering approach represents an effective cell delivery strategy and induces modulations in cell function which may demonstrate pathological significance.
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