Abstract
Adipose‐derived mesenchymal stromal cells (AdMSC) release numerous soluble factors capable of stimulating angiogenesis. Improved methods for delivering these cells to maximize their potency are now sought that ideally they retain viable cells in the target tissue while promoting the secretion of angiogenic factors. Substrate surface topography is a parameter that can be used to manipulate the behavior of AdMSC but challenges exist with translating this parameter into materials compatible with minimally invasive delivery into tissues for in situ delivery of the angiogenic secretome. The current study investigates three compositions of hierarchically structured, porous biodegradable microcarriers for the culture of AdMSC and the influence of their surface topographies on the angiogenic secretome. All three compositions perform well as cell microcarriers in xeno‐free conditions. The attached AdMSC retain their capacity for subsequent trilineage differentiation. The secretome of AdMSC attached to the microcarriers consists of multiple proangiogenic factors, including significantly elevated levels of vascular endothelial growth factor, which stimulates angiogenesis in vitro. The unique properties of hierarchically structured, porous biodegradable microcarriers investigated in this study offer a radically transformative approach for achieving targeted in vivo delivery of AdMSC and enhancing the potency of their proangiogenic activity to induce neovascularization in ischemic tissue.
Highlights
Introduction their paracrine activitiesphysiological manip ulation, such as exposure to hypoxic conditions, has beenMesenchymal stromal cells (MSC) secrete a plurality of mole shown to increase secretion of certain growth factors, such as cules, collectively called the MSC secretome, which include a vascular endothelial growth factor (VEGF), fibroblast growth heterogeneous pool of soluble proteins, free nucleic acids, lipids factor 2 (FGF-2), hepatocyte growth factor (HGF) and antiinflammatory molecules
The paracrine activity of MSC is affected by the local cellular micro environment, which comprises a plethora carriers investigated in this study offer a radically transformative approach for of biochemical, mechanical and physical achieving targeted in vivo delivery of Adipose-derived mesenchymal stromal cells (AdMSC) and enhancing the potency of their proangiogenic activity to induce neovascularization in ischemic tissue
The current study investigated whether highly porous, biodegradable PLGA thermally induced phase separation (TIPS) microcar riers could be used for culture of AdMSC and manipulation of their secretome toward proangiogenic activity
Summary
Introduction their paracrine activitiesphysiological manip ulation, such as exposure to hypoxic conditions, has beenMesenchymal stromal cells (MSC) secrete a plurality of mole shown to increase secretion of certain growth factors, such as cules, collectively called the MSC secretome, which include a vascular endothelial growth factor (VEGF), fibroblast growth heterogeneous pool of soluble proteins, free nucleic acids, lipids factor 2 (FGF-2), hepatocyte growth factor (HGF) and antiinflammatory molecules (reviewed in ref. [13]). Mesenchymal stromal cells (MSC) secrete a plurality of mole shown to increase secretion of certain growth factors, such as cules, collectively called the MSC secretome, which include a vascular endothelial growth factor (VEGF), fibroblast growth heterogeneous pool of soluble proteins, free nucleic acids, lipids factor 2 (FGF-2), hepatocyte growth factor (HGF) and antiinflammatory molecules Li Department of Chemistry University College London cell culture may influence the MSC secretome. 3D cell culture in the form of multicellular spheroids results in elevated secretion profiles of proangiogenic, anti-inflammatory and/or antiapoptotic factors compared with the secretome derived from conventional monolayer culture.[14] mechanical stimulation (such as bioreactor-mediated mechan ical loading) of MSC results in a significant enhancement of their proangiogenic paracrine activity compared with unstimu lated MSC.[15] Increased understanding of the physicochemical
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