Tissue engraftment of hypoxic-preconditioned adipose-derived stem cells improves flap viability.

Abstract

Adipose-derived stem cells (ASCs) have the ability to release multiple growth factors in response to hypoxia. In this study, we investigated the potential of ASCs to prevent tissue ischemia. We found conditioned media from hypoxic ASCs had increased levels of vascular endothelial growth factor (VEGF) and enhanced endothelial cell tubule formation. To investigate the effect of injecting rat ASCs into ischemic flaps, 21 Lewis rats were divided into three groups: control, normal oxygen ASCs (10(6) cells), and hypoxic preconditioned ASCs (10(6) cells). At the time of flap elevation, the distal third of the flap was injected with the treatment group. At 7 days post flap elevation, flap viability was significantly improved with injection of hypoxic preconditioned ASCs. Cluster of differentiation-31-positive cells were more abundant along the margins of flaps injected with ASCs. Fluorescent labeled ASCs localized aside blood vessels or throughout the tissue, dependent on oxygen preconditioning status. Next, we evaluated the effect of hypoxic preconditioning on ASC migration and chemotaxis. Hypoxia did not affect ASC migration on scratch assay or chemotaxis to collagen and laminin. Thus, hypoxic preconditioning of injected ASCs improves flap viability likely through the effects of VEGF release. These effects are modest and represent the limitations of cellular and growth factor-induced angiogenesis in the acute setting of ischemia.

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Citation

Published Version (Please cite this version)

10.1111/j.1524-475X.2012.00854.x

Publication Info

Hollenbeck, Scott T, Annika Senghaas, Issei Komatsu, Ying Zhang, Detlev Erdmann and Bruce Klitzman (2012). Tissue engraftment of hypoxic-preconditioned adipose-derived stem cells improves flap viability. Wound Repair Regen, 20(6). pp. 872–878. 10.1111/j.1524-475X.2012.00854.x Retrieved from https://hdl.handle.net/10161/10341.

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Scholars@Duke

Erdmann

Detlev Erdmann

Professor of Surgery
Klitzman

Bruce Klitzman

Associate Professor Emeritus in Surgery

Our overriding interests are in the fields of tissue engineering, wound healing, biosensors, and long term improvement of medical device implantation. My basic research interests are in the area of physiological mechanisms of optimizing substrate transport to tissue. This broad topic covers studies on a whole animal, whole organ, hemorheological, microvascular, cellular, ultrastructural, and molecular level. The current projects include:
1) control of blood flow and flow distribution in the microcirculation,
2) the effects of long-term synthetic and biologic implants on substrate transport to tissues,
3) tissue engineering; combining isolated cells, especially adult stem cells, with biomaterials to form specialized composite structures for implantation, with particular emphasis on endothelial cell physiology and its alteration by isolation and seeding on biomaterials.
4) decreasing the thrombogenicity of synthetic blood vessels and other blood-contacting devices, and improving their overall performance and biocompatibility.
5) reducing tissue damage resulting from abnormal perfusion (e.g., relative ischemia, anoxia, etc.) and therapies which minimize ischemic damage.
6) biosensor function, particularly glucose sensors in normal and diabetics.
7) measurement of tissue blood flow and oxygenation as an indicator of tissue viability and functional potential.
8) development of biocompatible materials for soft tissue reconstruction or augmentation.
9) improving performance of glaucoma drainage devices by directing a more favorable foreign body reaction
10) wound healing; particularly internal healing around foreign materials and the effect and prevention of microbes around implanted devices.


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