title: 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.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. scott.hollenbeck@duke.edu
authors.forename: Scott T
authors.initials: ST
authors.lastname: Hollenbeck
authors.forename: Annika
authors.initials: A
authors.lastname: Senghaas
authors.forename: Issei
authors.initials: I
authors.lastname: Komatsu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Detlev
authors.initials: D
authors.lastname: Erdmann
authors.forename: Bruce
authors.initials: B
authors.lastname: Klitzman
mesh_terms: D017667:Adipocytes / Q000473:pathology*; D000273:Adipose Tissue / Q000166:cytology / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002633:Chemotaxis; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007511:Ischemia / Q000473:pathology; D008297:Male; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat