Porous nanofibrous poly(l-lactic acid) scaffolds supporting cardiovascular progenitor cells for cardiac tissue engineering

Abstract

Myocardial infarction (MI) is the irreversible necrosis of heart with approximately 1.5 million cases every year in the United States. Tissue engineering offers a promising strategy for cardiac repair after MI. However, the optimal cell source for heart tissue regeneration and the ideal scaffolds to support cell survival, differentiation, and integration, remain to be developed. To address these issues, we developed the technology to induce cardiovascular progenitor cells (CPCs) derived from mouse embryonic stem cells (ESCs) towards desired cardiomyocytes as well as smooth muscle cells and endothelial cells. We fabricated extracellular matrix (ECM)-mimicking nanofibrous poly(l-lactic acid) (PLLA) scaffolds with porous structure of high interconnection for cardiac tissue formation. The CPCs were seeded into the scaffolds to engineer cardiac constructs in vitro. Fluorescence staining and RT-PCR assay showed that the scaffolds facilitated cell attachment, extension, and differentiation. Subcutaneous implantation of the cell/scaffold constructs in a nude mouse model showed that the scaffolds favorably supported survival of the grafted cells and their commitment to the three desired lineages in vivo. Thus, our study suggested that the porous nanofibrous PLLA scaffolds support cardiac tissue formation from CPCs. The integration of CPCs with the nanofibrous PLLA scaffolds represents a promising tissue engineering strategy for cardiac repair.

Polyethylenimine: A new differentiation factor to endothelial/cardiac tissue

“…Polyethylenimine due to the presence of amine structural units is categorized as a polyamine. It is demonstrated that polyamines such as arginine, putrescine, spermidine, and spermine can interact with cellular components such as DNA which will enhance cell growth, endothelial gene expression, such as an increase in expression of VEGF, and angiogenesis similar to angiogenesis in cancer . In this experiment, scaffolds have been fabricated using the electrospinning technique.…”

Biodegradable Nanofibrous Temperature‐Responsive Gelling Microspheres for Heart Regeneration

“…Consistent with this notion, we previously showed porous and nanofibrous scaffolds to enhance cardiac differentiation over control non‐nanofibrous scaffolds. [ 29 ] CM delivery using NF microspheres without gelling property resulted in significantly lower enhancement in CM engraftment (3,4‐fold enhancement over CM only, unpublished data) compared to the approximately tenfold CM engraftment increase using the NF‐GMS hydrogel. Various hydrogels were reported to improve CM retention or protection, [ 28,30 ] but their improvements were not at the same level as NF‐GMS in this work.…”

Reconstruction of structure and function in tissue engineering of solid organs: Toward simulation of natural development based on decellularization

“…Despite the regenerative potential of certain cardiac cell types such as cardiomyocytes and cardiac progenitors, they are not appropriate for heart tissue engineering due to scarce sources, difficult isolation, and low proliferation rate (Ptaszek, Mansour, Ruskin, & Chien, ). Therefore, stem or progenitor cells including ESCs (Liu et al, ), iPSCs (Tan et al, ), and adult stem cells (Golpanian, Wolf, Hatzistergos, & Hare, ) are promising cell sources for producing cardiomyocytes. The addition of other cell types such as vascular and connective tissue elements, compared with constructs based on single‐cell culture, can enhance the survival and maturation of cardiomyocytes, promote the formation of vascular network, and strengthen the mechanical integrity (Caspi et al, ).…”