Isolation of tissue-resident endothelial stem cells and their use in regenerative medicine

Abstract

Background During sprouting angiogenesis, stalk cells, localized behind tip cells, generate endothelial cells (ECs) for the elongation of new vessels. We hypothesized that stalk cells may have endothelial progenitor cell properties because of their highly proliferative ability. We conducted Hoechst dye DNA staining in ECs of preexisting blood vessels from hind limb muscle and found that endothelial-side population (E-SP) cells, which efflux Hoechst rapidly with abundant ABC transporters, show highly producing ability of ECs. We previously showed the existence of E-SP cells in hind limb muscle, retina, and liver, but not in other tissues such as adipose tissue, skin, and placenta. Methods We investigated the existence of E-SP cells and analyzed their proliferative ability among CD31 + CD45 − ECs from adipose tissue, skin, and placenta of adult mice. We also analyzed the neovascular formation of E-SP cells from adipose tissue in vivo. Results We detected E-SP cells in all tissues examined. However, by in vitro colony formation analysis on OP9 cells, we found that E-SP cells from adipose tissue and skin, but not from placenta, have highly proliferative ability. Moreover, E-SP cells from adipose tissue could contribute to the neovascular formation in hind limb ischemia model. Conclusion The adipose tissue and skin are available sources to obtain endothelial stem cells for conducting therapeutic angiogenesis in regenerative medicine.

Long-term in vivo survival of 3D-bioprinted human lipoaspirate-derived adipose tissue: proteomic signature and cellular content

“…Recent perception of adipose tissue as merely a passive source of energy and insulation has been challenged and revised. Adipose tissue is now defined as an endocrine organ with extensive networks of auto-paracrine signalling pathways [ 6 , 7 ], as well as a rich variety of cell types, including ASCs and EPCs [ 26 , 27 ]. The reservoir of multipotent adult mesenchymal stem cells found in adipose tissue (i.e.…”

Differential phenotype and behavior in culture of CD34 positive cells from peripheral blood and adipose tissue

“…Adipose tissue has been found to be an abundant source of progenitor cells [ 18 , 20 ]. Pham et al suggested the existence of a distinct EPC phenotype within adipose tissue [ 17 , 19 ]. Where the stromal vascular fraction is isolated from adipose tissue and placed in culture, rapid early appearance of endothelial cells has been noted by our group and by others [ 20 , 23 , 24 , 25 ].…”

“…In recent years, great interest has developed in adipose tissue (AT) as a source of stem and progenitor cells [ 16 ], and there is substantial evidence for the stromal vascular fraction (SVF) from AT to yield cells capable of endothelial differentiation, and to promote angiogenesis in a hindlimb ischemia model [ 17 , 18 , 19 , 20 ]. These findings are supportive of the hypothesis that adipose tissue may be a source of true endothelial progenitor cells.…”

CD157: From Myeloid Cell Differentiation Marker to Therapeutic Target in Acute Myeloid Leukemia

“…The general picture that emerges from studies performed in humans and mice indicates that CD157 expression is not restricted to the myeloid compartment but extends to tissues of different origins, such as gut [34], lung [35], eye [36], blood vascular system [37], and brain [16]. Of note, its expression frequently marks cell stemness [38][39][40].…”

“…Although for a long time CD157 has remained the neglected member of the ARC family, in recent years, it has gained interest as the functional repertoire of CD157 has greatly expanded from immunity to cancer and metabolism, with a common thread of cell adhesion/migration and 'stemness' connecting all functions [16,[37][38][39][40].…”