Dataset Information

Elderly Patient-Derived Endothelial Cells for Vascularization of Engineered Muscle.

ABSTRACT: In vitro prevascularization of engineered tissue constructs promises to enhance their clinical applicability. We hypothesize that adult endothelial cells (ECs), isolated from limb veins of elderly patients, bear the vasculogenic properties required to form vascular networks in vitro that can later integrate with the host vasculature upon implantation. Here, we show that adult ECs formed vessel networks that were more developed and complex than those formed by human umbilical vein endothelial cells (HUVECs) seeded with various supporting cells on three-dimensional (3D) biodegradable polymer scaffolds. In parallel, secreted levels of key proangiogenic cytokines were significantly higher in adult EC-bearing scaffolds as compared to HUVEC scaffolds. As a proof of concept for applicability of this model, adult ECs were co-seeded with human myoblasts as well as supporting cells and successfully formed a branched network, which was surrounded by aligned human myotubes. The vascularized engineered muscle tissue implanted into a full-thickness defect in immunodeficient mice remained viable and anastomosed with the host vasculature within 9 days of implantation. Functional "chimeric" blood vessels and various types of anastomosis were observed. These findings provide strong evidence of the applicability of adult ECs in construction of clinically relevant autologous vascularized tissue.

SUBMITTER: Perry L

PROVIDER: S-EPMC5383646 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Elderly Patient-Derived Endothelial Cells for Vascularization of Engineered Muscle.

Perry Luba L Flugelman Moshe Y MY Levenberg Shulamit S

Molecular therapy : the journal of the American Society of Gene Therapy 20170306 4

In vitro prevascularization of engineered tissue constructs promises to enhance their clinical applicability. We hypothesize that adult endothelial cells (ECs), isolated from limb veins of elderly patients, bear the vasculogenic properties required to form vascular networks in vitro that can later integrate with the host vasculature upon implantation. Here, we show that adult ECs formed vessel networks that were more developed and complex than those formed by human umbilical vein endothelial cel ...[more]

PMID: 28279644

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Project description:BackgroundHemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner.ResultsIn this study, we constructed a hemostatic sponge OBNC-DFO by fermentation of Komagataeibacter xylinus combined with TEMPO oxidation to obtain oxidized bacterial nanocellulose (OBNC). Then angiogenetic drug desferrioxamine (DFO) was grafted through an amide bond, and it promoted clot formation and activated coagulation reaction by rapid blood absorption due to the high total pore area (approximately 42.429 m2/g measured by BET). The further release of DFO stimulated the secretion of HIF-1α and the reconstruction of blood flow, thus achieving rapid hemostasis and vascularization in damaged tissue. This new hemostatic sponge can absorb water at a rate of approximate 1.70 g/s, rapidly enhancing clot formation in the early stage of hemostasis. In vitro and in vivo coagulation experiments (in rat tail amputation model and liver trauma model) demonstrated superior pro-coagulation effects of OBNC and OBNC-DFO to clinically used collagen hemostatic sponges (COL). They promoted aggregation and activation of red blood cells and platelets with shorter whole blood clotting time, more robust activation of endogenous coagulation pathways and less blood loss. In vitro cellular assays showed that OBNC-DFO prevailed over OBNC by promoting the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the release of DFO enhanced the secretion of HIF-1α, further strengthening vascularization in damaged skin. In the rat skin injury model, 28 days after being treated with OBNC-DFO, skin appendages (e.g., hair follicles) became more intact, indicating the achievement of structural and functional regeneration of the skin.ConclusionThis hemostatic and vascularization-promoting oxidized bacterial nanocellulose hemostatic sponge, which rapidly activates coagulation pathways and enables skin regeneration, is a highly promising hemostatic and pro-regenerative repair biomaterial.

Dataset Information

Elderly Patient-Derived Endothelial Cells for Vascularization of Engineered Muscle.

Publications

Elderly Patient-Derived Endothelial Cells for Vascularization of Engineered Muscle.

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