Significance of Cellular Cross-Talk in Stromal Vascular Fraction of Adipose Tissue in Neovascularization

Abstract

Adult stem cell-based therapy has been regarded as a promising treatment for tissue ischemia because of its ability to promote new blood vessel formation. Bone marrow-derived mesenchymal stem cells are the most used angiogenic cells for therapeutic neovascularization, yet the side effects and low efficacy have limited their clinical application. Adipose stromal vascular fraction is an easily accessible, heterogeneous cell system comprised of endothelial, stromal, and hematopoietic cell lineages, which has been shown to spontaneously form robust, patent, and functional vasculatures in vivo. However, the characteristics of each cell population and their specific roles in neovascularization remain an area of ongoing investigation. In this review, we summarize the functional capabilities of various stromal vascular fraction constituents during the process of neovascularization and attempt to analyze whether the cross-talk between these constituents generates a synergetic effect, thus contributing to the development of new potential therapeutic strategies to promote neovascularization.

Keywords: adipose tissue; adult stem cell; endothelial progenitor cell; ischemia; mesenchymal stem cell; myeloid cell; neovascularization, physiologic.

Figure 1:

The possible mechanisms underlying neovascularization induced by SVF implantation:

1. ECFCs can proliferate and differentiate into ECs and supply “building blocks” for tube network formation.

2. ADSCs promote ECFC proliferation differentiation by secreting VEGF, HGF, placental growth factor (PGF), FGF-2, TGF-β, and angiopoietin-1 and through cell-cell contact.

3. ADSCs and ECs co-produce ECM proteins; ADSCs can differentiate into pericytes, both of which stabilize the newly formed vessel structure.

4. MACs enhance angiogenesis tubulogenesis assay through the release of IL-8, MCP1, MMP9, and VEGF2; correspondingly, ECFCs showed significantly higher expressions of the receptors for VEGF (KDR) and IL-8 (CXCR-1).

5. Cytokines may induce the resident or circulating ECFCs to aggregate in the ischemic area and promote neovascularization; the angiogenic factor gradient could induce EC tip cell proliferation and migration.