Tissue engraftment of hypoxic-preconditioned adipose-derived stem cells improves flap viability.
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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.
Culture Media, Conditioned
Intercellular Signaling Peptides and Proteins
Rats, Inbred Lew
Stem Cell Transplantation
Vascular Endothelial Growth Factor A
Published Version (Please cite this version)10.1111/j.1524-475X.2012.00854.x
Publication InfoHollenbeck, Scott T; Senghaas, Annika; Komatsu, Issei; Zhang, Ying; Erdmann, Detlev; & Klitzman, Bruce (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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Professor of Surgery
Associate Professor of Surgery
Breast Cancer, Adipose Biology, Lower Extremity Reconstruction
Associate Professor of 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 distribu
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