Differentiation, metabolism and cardioprotective secretory functions of human cardiac stromal cells from ischemic and endocarditis patients

This study investigates the characteristics of cardiac mesenchymal stem cell-like cells (CMSCLCs) isolated from the right atrial appendage of human donors with ischemia and a young patient with endocarditis (NE-CMSCLCs). Typical CMSCLCs from ischemic heart patients were derived from coronary artery bypass grafting procedures, and compared against bone marrow mesenchymal stromal cells (BM-MSCs). NE-CMSCLCs had a normal immunophenotype but exhibited enhanced osteogenic differentiation potential, rapid proliferation, reduced senescence, reduced glycolysis, and lower reactive oxygen species generation after oxidative stress compared to typical ischemic CMSCLCs. These differences suggest a unique functional status of NE-CMSCLCs, influenced by the donor health condition. Despite large variances in their paracrine secretome, NE-CMSCLCs retained therapeutic potential, as indicated by their ability to protect hypoxia/reoxygenation-injured human cardiomyocytes, albeit less effectively than typical CMSCLCs. This research describes a unique cell phenotype and underscores the importance of donor health status in the therapeutic efficacy of autologous cardiac cell therapy

Degradable Biocompatible Porous Microtube Scaffold for Extended Donor Cell Survival and Activity

Cell therapy has significant therapeutic potential but is often limited by poor donor cell retention and viability at the host implantation site. Biomaterials can improve cell retention by providing cells with increased cell–cell and cell–matrix contacts and materials that allow three-dimensional cell culture to better recapitulate native cell morphology and function. In this study, we engineered a scaffold that allows for cell encapsulation and sustained three-dimensional cell culture. Since cell therapy is largely driven by paracrine secretions, the material was fabricated by electrospinning to have a large internal surface area, micrometer-thin walls, and nanoscale surface pores to allow for nutrient exchange without early cell permeation. The material is degradable, which allows for less invasive removal of the implant. Here, a biodegradable poly(lactic-co-glycolic acid) (PLGA) microtube array membrane was fabricated. In vitro testing showed that the material supported the culture of human dermal fibroblasts for at least 21 days, with paracrine secretion of pro-angiogenic FGF2. In vivo xenotransplantation of human cells in an immunocompetent mouse showed that donor cells could be maintained for more than one month and the material showed no obvious toxicity. Analysis of gene expression and tissue histology surrounding the implant showed that the material produced muted inflammatory and immune responses compared to a permanent implant and increased markers of angiogenesis