title: Rescue of the mucocutaneous manifestations by human cord blood derived nonhematopoietic stem cells in a mouse model of recessive dystrophic epidermolysis bullosa.
abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin blistering disease caused by mutations in COL7A1-encoding type VII collagen (C7). Currently, there is no curative therapy for patients with RDEB. Our previous studies demonstrated that human umbilical cord blood (HUCB) derived unrestricted somatic stem cells (USSCs) express C7 and facilitate wound healing in a murine wounding model. The primary objective of this study is to investigate the therapeutic functions of USSCs in the C7 null (Col7a1(-/-) ) C57BL6/J mice, a murine model of RDEB. We demonstrated that intrahepatic administration of USSCs significantly improved the blistering phenotype and enhanced the life span in the recipients. The injected USSCs trafficked to the sites of blistering and were incorporated in short-term in the recipients' skin and gastrointestinal tract. Consistent with an overall histological improvement in the epidermal-dermal adherence following USSC treatment, the expression of C7 at the basement membrane zone was detected and the previously disorganized integrin α6 distribution was normalized. We also demonstrated that USSCs treatment induced an infiltration of macrophages with a regenerative "M2" phenotype. Our data suggest that HUCB-derived USSCs improved the RDEB phenotype through multiple mechanisms. This study has warranted future clinical investigation of USSCs as a novel and universal allogeneic stem cell donor source in selected patients with RDEB.
authors: Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
authors: Yanling
authors: Y
authors: Liao
authors: Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
authors: Larisa
authors: L
authors: Ivanova
authors: Department of Surgery, Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin, People's Republic of China.
authors: Hongwen
authors: H
authors: Zhu
authors: Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
authors: Ashlin
authors: A
authors: Yahr
authors: Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
authors: Janet
authors: J
authors: Ayello
authors: Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
authors: Carmella
authors: C
authors: van de Ven
authors: Department of Pediatrics, New York Medical College, Valhalla, New York, USA.
authors: Ahmed
authors: A
authors: Rashad
authors: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors: Jouni
authors: J
authors: Uitto
authors: Department of Dermatology, Columbia University Medical Center, New York, New York, USA.
authors: Angela M
authors: AM
authors: Christiano
authors: Department of Pediatrics, New York Medical College, Valhalla, New York, USA.|Department of Medicine, New York Medical College, Valhalla, New York, USA.|Department of Pathology, New York Medical College, Valhalla, New York, USA.|Department of Immunology and Microbiology, New York Medical College, Valhalla, New York, USA.|Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, USA.
authors: Mitchell S
authors: MS
authors: Cairo
mesh_terms: D000818:Animals; D024143:Collagen Type VII / Q000172:deficiency / Q000378:metabolism; D004195:Disease Models, Animal; D016108:Epidermolysis Bullosa Dystrophica / Q000628:therapy*; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D012867:Skin / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D014945:Wound Healing / Q000502:physiology
chemical_list: C583886:Col7a1 protein, mouse; D024143:Collagen Type VII
keywords: Cytotherapy; Human cord blood stem cells; Inherited diseases; Skin blistering diseases; Stem cell transplantation