title: Adipose-derived aldehyde dehydrogenase-expressing cells promote dermal regenerative potential with collagen-glycosaminoglycan scaffold.
abstract: Aldehyde dehydrogenase (ALDH) is an enzyme that plays an important role in retinoid metabolism and highly expressed in stem cells. This study isolated ALDH-expressing cells from subcutaneous adipose tissue and investigated their potential to enhance healing in a full-thickness skin wound in rats by co-implanting them with collagen-glycosaminoglycan (c-GAG) scaffolds. ALDH-positive cells were isolated by a fluorescence-activated cell sorting technique from Lewis rat's stromal-vascular-fraction (SVF) and transplanted with c-GAG scaffolds in a rat full-thickness skin wound model. At 7 days after surgery, the microscopic appearance of c-GAG scaffolds seeded with ALDH-positive was compared with those of uncultured-SVF, and cultured-SVF adipose-derived stromal cells (ASCs). The thickness of cellular ingrowth in the ASC group (630 ± 180 μm) was significantly thicker than that in the control (390 ± 120 μm) or SVF (380 ± 140 μm) groups, but non-significantly thicker than that in the ALDH-positive group (570 ± 220 μm). The thickness of regenerated collagen layer was significantly thicker in the ALDH-positive group (160 ± 110 μm) than in the ASCs (81 ± 41 μm), the control (65 ± 24 μm), or SVF (64 ± 34 μm) groups. Immunofluorescent staining with CD31 proved that transplanted ALDH-positive cells differentiated into vascular endothelial cells in c-GAG scaffolds. Combined transplantation with c-GAG scaffolds and adipose-derived ALDH-positive cells promoted dermal regeneration, giving a possibility that ALDH-positive cells would greatly shorten the waiting period before secondary autologous skin grafting was possible.
authors.affiliation: The Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School.
authors.forename: Hajime
authors.initials: H
authors.lastname: Matsumine
authors.affiliation: The Department of Pathology, Brigham and Women's Hospital, Harvard Medical School.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Numakura
authors.affiliation: Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsunoda
authors.affiliation: The Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Rui
authors.initials: R
authors.lastname: Matsumine
authors.affiliation: The Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School.
authors.forename: Mihail
authors.initials: M
authors.lastname: Climov
authors.affiliation: The Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giatsidis
authors.affiliation: Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vikas P
authors.initials: VP
authors.lastname: Sukhatme
authors.affiliation: The Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School.
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D020405:Dermis / Q000503:physiopathology*; D006025:Glycosaminoglycans / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000502:physiology*; D016038:Skin Transplantation; D050151:Subcutaneous Fat / Q000166:cytology / Q000378:metabolism*; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000503:physiopathology
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen; D000444:Aldehyde Dehydrogenase