IFATS Collection: The Role of Human Adipose-Derived Stromal Cells in Inflammatory Microvascular Remodeling and Evidence of a Perivascular Phenotype

Abstract

A growing body of literature suggests that human adiposederived stromal cells (hASCs) possess developmental plasticity both in vitro and in vivo, and might represent a viable cell source for therapeutic angiogenesis and tissue engineering. We investigate their phenotypic similarity to perivascular cell types, ability to contribute to in vivo microvascular remodeling, and ability to modulate vascular stability. We evaluated hASC surface expression of vascular and stem/ progenitor cell markers in vitro, as well as any effects of platelet-derived growth factor B chain (PDGF-BB) and vascular endothelial growth factor 165 on in vitro hASC migration. To ascertain in vivo behavior of hASCs in an angiogenic environment, hASCs were isolated, expanded in culture, labeled with a fluorescent marker, and injected into adult nude rat mesenteries that were stimulated to undergo microvascular remodeling. Ten, 30, and 60 days after injection, tissues from anesthetized animals were harvested and processed with immunohistochemical techniques to determine hASC quantity, positional fate in relation to microvessels, and expression of endothelial and perivascular cell markers. After 60 days, 29% of hASCs exhibited perivascular morphologies compared with 11% of injected human lung fibroblasts. hASCs exhibiting perivascular morphologies also expressed markers characteristic of vascular pericytes: smooth muscle ␣-actin (10%) and neuron-glia antigen 2 (8%). In tissues treated with hASCs, vascular density was significantly increased over age-matched controls lacking hASCs. This study demonstrates that hASCs express pericyte lineage markers in vivo and in vitro, exhibit increased migration in response to PDGF-BB in vitro, exhibit perivascular morphology when injected in vivo, and contribute to increases in microvascular density during angiogenesis by migrating toward vessels. STEM CELLS

Concise Review: Adipose-Derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation

“…Some have used the protein Pref1, first identified on murine 3T3-L1 preadipocytes, as a putative ASC marker [24]. Others have reported the use of pericytic markers such as plateletderived growth factor receptor b and 3G5 [23,[25][26][27][28]. Finally, combinatorial phage display approaches have associated the presence of a 5 b 1 integrin with ASCs [29].…”

Modeling early stage bone regeneration with biomimetic electrospun fibrinogen nanofibers and adipose-derived mesenchymal stem cells

“…Furthermore, ASCs, as with MSCs from other tissue sources, secrete numerous growth factors implicated in tissue development and regeneration [18]. As progenitor cells of a perivascular origin (such as in the periosteum) are major contributors to primary bone healing, the putative pericyte origin for ASCs, as well as their association with a perivascular niche [19][20][21][22][23], suggests a role for ASCs as a model for osteoblastogenesis.…”

Isolation of endothelial progenitor cells from human adipose tissue

“…However, some studies have rejected this notion, and refute that ADSCs can differentiate into ECs/EPCs (Kondo et al, 2009). Several recent studies have indicated that adipose-derived regenerative cells (ADRCs) can differentiate into pericytes in vitro and in vivo (Amos et al, 2008;Traktuev et al, 2008;Zannettino et al, 2008). However, transplantation of ADSCs, as well as SVFs, have demonstrated neoangiogenesis and vasculogenesis in vivo (Guo et al, 2016;Zhong et al, 2016).…”