Stem cell‐based therapies for cardiac diseases: The critical role of angiogenic exosomes

Abstract

Finding effective treatments for cardiac diseases is among the hottest subjects in medicine; cell-based therapies have brought great promises for managing a broad range of life-threatening heart complications such as myocardial infarction. After clarifying the critical role of angiogenesis in tissue repair and regeneration, various stem/progenitor cell were utilized to accelerate the healing of injured cardiac tissue. Embryonic, fetal, adult, and induced pluripotent stem cells have shown the appropriate proangiogenic potential for tissue repair strategies. The capability of stem cells for differentiating into endothelial lineages was initially introduced as the primary mechanism involved in improving angiogenesis and accelerated heart tissue repair. However, recent studies have demonstrated the leading role of paracrine factors secreted by stem cells in advancing neo-vessel formation. Genetically modified stem cells are also being applied for promoting angiogenesis regarding their ability to considerably overexpress and secrete angiogenic bioactive molecules. Yet, conducting further research seems necessary to precisely identify molecular mechanisms behind the proangiogenic potential of stem cells, including the signaling pathways and regulatory molecules such as microRNAs. In conclusion, stem cells' pivotal roles in promoting angiogenesis and consequent improved cardiac healing and remodeling processes should not be ignored, especially in the case of stem cellderived extracellular vesicles.

Characterization of Macroporous Polycaprolactone/Silk Fibroin/Gelatin/Ascorbic Acid Composite Scaffolds and In Vivo Results in a Rabbit Model for Meniscus Cartilage Repair

“…The current study assumes that the mixture of gelatin and silk with AA and PCL provides a better biomaterial with appropriate mechanical strength, flexibility, water absorption, biocompatibility, and biological interactions. Among all cell sources, mesenchymal stem cells (MSCs), because of their capability of differentiation to different mesenchymal lineages, anti-inflammatory, and immunomodulatory features [28][29][30][31][32][33][34] are of particular interest. Adipose-derived mesenchymal stem cells (ASCs) obtained from the infrapatellar fat pad of the knee can differentiate into chondrocytes and produce proteoglycans and type II collagen.…”

Stem cell‐mediated angiogenesis in skin tissue engineering and wound healing

“…Angiogenesis is a complicated biological process that comprises several interactions between vascular cells and the extracellular environment. The critical role of stem/progenitor cells in enhancing neovessel formation has been previously identified as they can induce angiogenesis through either direct differentiation towards ECs or secretion of pro‐angiogenic EVs 27–30 . The latter is currently acknowledged as the main biological phenomenon behind promoted angiogenesis and accelerated wound healing 31–33 …”

“…The critical role of stem/progenitor cells in enhancing neovessel formation has been previously identified as they can induce angiogenesis through either direct differentiation towards ECs or secretion of pro-angiogenic EVs. [27][28][29][30] The latter is currently acknowledged as the main biological phenomenon behind promoted angiogenesis and accelerated wound healing. [31][32][33] Prior experiments have shown that stem cells may differentiate into ECs under specific conditions, including co-culturing with an extracellular matrix (ECM), exposure to different GFs (e.g., VEGF), preconditioning in a hypoxic environment, and implementing mechanical stimuli (e.g., shear stress).…”

Islet-1 Mesenchymal Stem Cells-Derived Exosome-Incorporated Angiogenin-1 Hydrogel for Enhanced Acute Myocardial Infarction Therapy

“…13,14 Thus, the therapy based on exosomes derived from MSCs (MSCs-Exo) has emerged as a potential therapeutic strategy for degenerative diseases. 15,16 However, exosomes are quickly eliminated by the blood circulation and only a small amount can be retained at the site of the disease. 17 Therefore, a sustainable method is needed to deliver exosomes and increase retention.…”

“…Transplanted heterogenic cells elicited an innate immune response, which resulted in their fast removal and limited short-term therapeutic delivery. Several studies demonstrated that exosomes generated from MSCs perform similarly favorable activities to the MSCs. , Additionally, as compared to stem cell treatment, exosomes may offer distinct benefits to minimize safety concerns. , Thus, the therapy based on exosomes derived from MSCs (MSCs-Exo) has emerged as a potential therapeutic strategy for degenerative diseases. , However, exosomes are quickly eliminated by the blood circulation and only a small amount can be retained at the site of the disease . Therefore, a sustainable method is needed to deliver exosomes and increase retention.…”