Effect of hypoxia on human adipose-derived mesenchymal stem cells and its potential clinical applications

Abstract

Human adipose-derived mesenchymal stem cells (hASCs) are an ideal cell source for regenerative medicine due to their capabilities of multipotency and the readily accessibility of adipose tissue. They have been found residing in a relatively low oxygen tension microenvironment in the body, but the physiological condition has been overlooked in most studies. In light of the escalating need for culturing hASCs under their physiological condition, this review summarizes the most recent advances in the hypoxia effect on hASCs. We first highlight the advantages of using hASCs in regenerative medicine and discuss the influence of hypoxia on the phenotype and functionality of hASCs in terms of viability, stemness, proliferation, differentiation, soluble factor secretion, and biosafety. We provide a glimpse of the possible cellular mechanism that involved under hypoxia and discuss the potential clinical applications. We then highlight the existing challenges and discuss the future perspective on the use of hypoxic-treated hASCs.

Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering

“…In fact, our chondrospheroid viability studies revealed larger numbers of dead cells in chondrospheroids cultured in normoxia than in those cultured in hypoxia. These results are in line with those of other authors, who have shown that hASC populations cultured in hypoxia exhibited better growth and survival [39][40][41], with few apoptotic events [17].…”

“…In line with this, the microenvironment of hASCs in vivo is also characterized by low oxygen pressure. It has been suggested that hypoxia reduces their potential for osteogenic differentiation [16] while promoting chondral extracellular matrix (ECM) formation [17]. In fact, chondrocyte markers such as SOX9, collagen type II (COL2A1) and aggrecan are positively regulated by hypoxic conditions [18].…”

Reduced culture temperature attenuates oxidative stress and inflammatory response facilitating expansion and differentiation of adipose-derived stem cells

“…Consequently, MSC culture at drastically higher atmospheric oxygen levels (21%), most commonly employed in culture protocols, leads to ROS overproduction, DNA damage, and genetic instability compared to culture under physiological oxygen levels (2-8%) [10][11][12][13][14]. Culture under physiological oxygen conditions also leads to increased proliferation and stem cell potency of both pluripotent [15][16][17] and adult stem cells [18][19][20][21][22][23][24]. Although adaptation of culture conditions to physiological oxygen levels to prevent excess ROS is appealing, reducing oxygen levels from atmospheric levels is demanding and pricy and requires specialized equipment.…”

Implications of Extracellular Matrix Production by Adipose Tissue-Derived Stem Cells for Development of Wound Healing Therapies

“…In particular, the use of hypoxic culture appears interesting, as several of the wound healing properties of ASCs appear to be enhanced [64,65]. Significantly, it was recently found that hypoxic culture of ASCs altered their expression profile of several proteins related to ECM structure and function [66].…”