Preservation of the cardiac function in infarcted rat hearts by the transplantation of adipose-derived stem cells with injectable fibrin scaffolds

Abstract

Cell-based therapy can improve cardiac function but is limited by the low cell retention and survival within ischemic tissues. Injectable cardiac tissue engineering aims to support cell-based therapies and enhance their efficacy for cardiac diseases. So far, no research has been devoted to studying the usefulness of the combination of fibrin glue (as scaffold) and adipose-derived stem cells (ADSCs) to treat myocardial infarction. In our study, the rat ADSCs were isolated from subcutaneous adipose tissues. The surface phenotype of these cells was analyzed by flow cytometry. The fibrin glue was then co-injected with ADSCs into the left ventricular wall of rat infarction models. The structure and functional consequences of transplantation were determined by detailed histological analysis and echocardiography. Most cultured ADSCs expressed CD105 and CD90, and were negative for CD34 and CD45. After injection, both the 24-h cell retention and four-week graft size were significantly higher and larger in the Fibrin + ADSCs group than those of the ADSCs group alone (P < 0.01). The heart function improved significantly in the Fibrin + ADSCs group compared with that of the ADSCs group four weeks after transplantation (P < 0.01). In addition, the arteriole densities within the infarcted area improved significantly in the Fibrin + ADSCs group compared with those in the ADSCs group four weeks after transplantation (P < 0.01). In conclusion, the ADSCs with the fibrin glue has the therapeutic potential to improve the function of infarcted hearts. The method of in situ injectable tissue engineering combining fibrin glue with ADSCs is promising clinically.

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…Conditioned media from hypoxia-treated ASCs can also improve cardiac function following infarction, possibly through their specific paracrine section of VEGF-A, bFGF, and TGF 1 [245]. Increased capillary densities/angiogenesis have also been reported using mouse ASCs injected into murine infarcts, with the ASCs taking up residence in the infarct area and EKGs showing stability of LVEF [246]; murine ASCs [247] or rat ASCs transplanted into rat infarcts resulting in significant improvement in heart function and tissue viability [248]; and human ASCs into rat infarcts, where not only increased peri-infarct capillary density is noted but increased numbers of nerve sprouts [249]. Finally, endothelial cells created from induced pluripotent ASCs (iPSCs) and injected into murine infarcts are found localized specifically around, but not directly integrated into, newly formed microvessels near the regenerating infarct region, suggesting paracrine action of these cells on the host vasculature [250].…”

Fibrin Glue Improves the Therapeutic Effect of MSCs by Sustaining Survival and Paracrine Function

“…Despite many animal and clinical studies, previous studies 19,21,22 have focused on the effect of fibrin glue on 1 proliferation and differentiation potential of MSCs, and consequential replacement of damaged tissue. However, the contribution of fibrin glue to the paracrine effects of MSCs has not been examined.…”

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart

“…17,20 Previous studies have also demonstrated that fibrin glue could improve the survival of injectable skeletal myoblasts, bone marrow cells, marrowderived cardiac stem cells, adipose-derived stem cells, and human induced pluripotent stem cell-derived cardiomyocytesin MI hearts. [21][22][23][24][25][26] Furthermore, injection of fibrin alone (without cells) could preserve cardiac function after MI and prevent negative LV remodeling. 27 Also, our previous report has demonstrated the positive role of platelet fibrin gel in cardiac repair after MI.…”