The Proangiogenic Potential of Mesenchymal Stem Cells and Their Therapeutic Applications

Abstract

Mesenchymal stem cells (MSCs) can be isolated from many tissue types and following in vitro culture expansion, large numbers of patient-specific or allogenic cells can be produced for clinical applications. MSCs exhibit anti-inflammatory and immunomodulatory properties and are identified as lacking major histocompatibility complex (MHC) class II molecules. Cellular-based approaches using MSCs to enhance new blood vessel formation have shown promise in preclinical models and preliminary clinical trials. Transplantation of MSCs in vivo has significantly enhanced the formation of new blood vessels and promoted the healing of chronic wounds. The proangiogenic potential of MSCs can be further enhanced through gene delivery such as vascular endothelial growth factor (VEGF) or endothelial nitric oxide synthase (eNOS) providing long-term therapeutic expression. In this chapter, we review recent advances on the isolation and characterization of MSCs and in vivo applications for promoting angiogenesis. Enhancement of angiogenesis is also required for improved healing in myocardial infarction and cerebral ischemia, and the use of MSCs in these areas will also be reviewed. Furthermore, the combination of MSCs with biomaterials has greatly improved their survival and potency with improved vascularization of tissue-engineered constructs and integration within the host. In summary, this chapter provides an overview of both the basic science supporting the proangiogenic properties of MSCs and their translational use.

Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

“…The MSCs produce pro-angiogenic cytokines such as hypoxia-inducible factor 1α (HIF-1α), angiogenin, angiopoietin I, angiopoietin II, angiopoietin IV, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), insulin-like growth factor 1 (IGF-1), VEGF, bFGF, PDGF, transforming growth factor-β (TGF-β), monocyte chemoattractant protein-1 (MCP-1), and as well as by triggering the VEGF-A signaling cascade. They are also capable of producing anti-angiogenic factors such as angiostatin and vasohibin ( Bandara et al, 2017 ; Rezaie et al, 2019 ; Maacha et al, 2020 ). Therefore, the balance between autocrine and paracrine secretion of pro-angiogenic and anti-angiogenic factors is responsible for promoting vasculogenesis and stabilizing the newly formed vessels by adjusting the permeability of new vessels through manipulation of cell-to-cell junctions ( Ghajar et al, 2006 ; Sorrell et al, 2009 ; Bussche and Van De Walle, 2014 ).…”

Current Progress in Vascular Engineering and Its Clinical Applications

“…As a result, using MSCs to fabricate TEVGs for clinical applications continues to be extensively investigated and documented. Nevertheless, there is still no MSC-derived TEVG that has reached clinical application from trials [66,74,[80][81][82].…”