Insulin-like growth factor 1 stimulates the angiogenic activity of adipose tissue–derived microvascular fragments

Abstract

Angiogenesis in adipose tissue is promoted by insulin-like growth factor 1 signaling. We analyzed whether this regulatory mechanism also improves the angiogenic activity of adipose tissue–derived microvascular fragments. Murine adipose tissue–derived microvascular fragments were cultivated for 24 h in the University of Wisconsin (UW) solution supplemented with vehicle, insulin-like growth factor 1, or a combination of insulin-like growth factor 1 and insulin-like growth factor–binding protein 4. Subsequently, we assessed their cellular composition, viability, proliferation, and growth factor expression. Moreover, cultivated adipose tissue–derived microvascular fragments were seeded onto collagen–glycosaminoglycan scaffolds, which were implanted into dorsal skinfold chambers to study their vascularization and incorporation. Insulin-like growth factor 1 increased the viability and growth factor expression of adipose tissue–derived microvascular fragments without affecting their cellular composition and proliferation. Accordingly, scaffolds containing insulin-like growth factor 1–stimulated adipose tissue–derived microvascular fragments exhibited an enhanced in vivo vascularization and incorporation. These positive insulin-like growth factor 1 effects were reversed by additional exposure of adipose tissue–derived microvascular fragments to insulin-like growth factor–binding protein 4. Our findings indicate that insulin-like growth factor 1 stimulation of adipose tissue–derived microvascular fragments is suitable to improve their vascularization capacity.

Engineering pericyte-supported microvascular capillaries in cell-laden hydrogels using stem cells from the bone marrow, dental pulp and dental apical papilla

“…However, understanding and controlling the complex heterotypic interactions that are required to establish a functional vasculature in engineered tissues remains a challenge. Much has been learned about the process of endothelial cell morphogenesis during angiogenesis and vasculogenesis, both during tissue development and remodeling [5][6][7][8] . However, control over the myriad interactions occurring between endothelial cells and other mural cells that contribute to the formation of functional vascular capillaries remains poorly understood.…”

Systemic low-dose erythropoietin administration improves the vascularization of collagen-glycosaminoglycan matrices seeded with adipose tissue-derived microvascular fragments

“…[35][36][37][38][39] Of interest, recent studies have shown that the vascularization capacity of MVF can be further enhanced by exposure to growth factors. 11,40 In fact, we found that a 24-h precultivation in medium supplemented with EPO improves the viability of MVF and promotes their reassembly into new microvascular networks after seeding onto CGAG matrices and in vivo implantation. 11 In the present follow-up study, we demonstrate that a systemically applied low dose of EPO induces similar effects without the necessity of a time-consuming pre-cultivation phase of MVF.…”

Engineering Functional Vascularized Beige Adipose Tissue from Microvascular Fragments of Models of Healthy and Type II Diabetes Conditions

“…In the case of obesity, network formation may lag adipose tissue enlargement, leading to lower vascular densities and hypoxia. 34,61 This hypoxic environment is thought to lead to an unbalance and overexpression of pro-angiogenic 62,63 and pro-inflammatory stimuli that can contribute to insulin resistance and diabetes development. 64 Overall, we demonstrate through histological and angiogenic gene expression analysis that Db-MVF have a reduced vascularization capacity.…”

“…64 Overall, we demonstrate through histological and angiogenic gene expression analysis that Db-MVF have a reduced vascularization capacity. Future work should explore this phenomenon further and investigate tools, such as the co-culture of MVF with supporting cells, 65,66 the preconditioning of MVFs, 43,55,62,63 changes to the seeding density, 67 or modification of the surrounding matrix 68,69 to help improve their performance, from an angiogenic standpoint when coming from a compromised source.…”