Overcoming hypoxia to improve tissue-engineering approaches to regenerative medicine

Abstract

The current clinical successes of tissue engineering are limited primarily to low-metabolism, acellular, pre-vascularized or thin tissues. Mass transport has been identified as the primary culprit, limiting the delivery of nutrients (such as oxygen and glucose) and removal of wastes, from tissues deep within a cellular scaffold. While strategies to develop sufficient vasculature to overcome hypoxia in vitro are promising, inconsistencies between the in vitro and the in vivo environments may still negate the effectiveness of large-volume tissue-engineered scaffolds. While a common theme in tissue engineering is to maximize oxygen supply, studies suggest that moderate oxygenation of cellular scaffolds during in vitro conditioning is preferable to high oxygen levels. Aiming for moderate oxygen values to prevent hypoxia while still promoting angiogenesis may be obtained by tailoring in vitro culture conditions to the oxygen environment the scaffold will experience upon implantation. This review discusses the causes and effects of tissue-engineering hypoxia and the optimization of oxygenation for the minimization of in vivo hypoxia.

Mesenchymal stem cell-derived CCL-9 and CCL-5 promote mammary tumor cell invasion and the activation of matrix metalloproteinases

“…[40][41][42] We, and others, have also investigated parameters from the local oxygen concentrations, the density of the ECM to the formation of chemokine heterodimers that can modulate cancer progression in in vitro models. [43][44][45] Furthermore, normal murine mammary gland (NMuMG) cells formed acini only in the presence of murine D1 mesenchymal stem cells whereas 4T1 murine tumor cells did not. 46 To determine whether chemokines present within the breast tumor microenvironment, especially CCL5 and CCL9, promoted the invasion of mammary tumor cells, we first determined the effects of molecules secreted by epithelial (NMuMG), tumor (4T1) cells, and mesenchymal D1 stem cells on NMuMG and 4T1 cell invasions using 2D and 3D culture conditions.…”

Females transplanted with ovaries subjected to hypoxic preconditioning show impair of ovarian function

“…Our study was based on the assumption that an in vitro hypoxia preconditioned ovary would respond better than an ovary exposed to hypoxia following transplantation, because it would have released environmental growth factors and free radicals, thus inducing early neoangiogenesis [30-33], which is crucial for preservation of the follicle pool. Our data, however, showed that overnight in vitro hypoxia before transplantation compromised graft viability with pronounced reduction in the number of viable ovarian follicles and functional corpora lutea.…”

Fibrotic Response to Biomaterials and all Associated Sequence of Fibrosis

“…In tissue engineering, this is a major design concern that is known to affect viability of cells within large constructs (Bland et al, 2013). In tissue engineering, this is a major design concern that is known to affect viability of cells within large constructs (Bland et al, 2013).…”