Open AccessEfficacy of Human Placental‐Derived Stem Cells in Collagen VII Knockout (Recessive Dystrophic Epidermolysis Bullosa) Animal Model
Author(s) -
Liao Yanling,
Ivanova Larisa,
Sivalenka Rajarajeswari,
Plumer Trevor,
Zhu Hongwen,
Zhang Xiaokui,
Christiano Angela M.,
McGrath John A.,
Gurney Jodi P.,
Cairo Mitchell S.
Publication year - 2018
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.17-0182
Subject(s) - anchoring fibrils , stem cell , epidermolysis bullosa , cord blood , progenitor cell , haematopoiesis , epidermolysis bullosa dystrophica , umbilical cord , pathology , immunology , biology , medicine , cancer research , basement membrane , microbiology and biotechnology
Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating inherited skin blistering disease caused by mutations in the COL7A1 gene that encodes type VII collagen (C7), a major structural component of anchoring fibrils at the dermal‐epidermal junction (DEJ). We recently demonstrated that human cord blood‐derived unrestricted somatic stem cells promote wound healing and ameliorate the blistering phenotype in a RDEB ( col7a1 −/− ) mouse model. Here, we demonstrate significant therapeutic effect of a further novel stem cell product in RDEB, that is, human placental‐derived stem cells (HPDSCs), currently being used as human leukocyte antigen‐independent donor cells with allogeneic umbilical cord blood stem cell transplantation in patients with malignant and nonmalignant diseases. HPDSCs are isolated from full‐term placentas following saline perfusion, red blood cell depletion, and volume reduction. HPDSCs contain significantly higher level of both hematopoietic and nonhematopoietic stem and progenitor cells than cord blood and are low in T cell content. A single intrahepatic administration of HPDSCs significantly elongated the median life span of the col7a1 −/− mice from 2 to 7 days and an additional intrahepatic administration significantly extended the median life span to 18 days. We further demonstrated that after intrahepatic administration, HPDSCs engrafted short‐term in the organs affected by RDEB, that is, skin and gastrointestinal tract of col7a1 −/− mice, increased adhesion at the DEJ and deposited C7 even at 4 months after administration of HPDSCs, without inducing anti‐C7 antibodies. This study warrants future clinical investigation to determine the safety and efficacy of HPDSCs in patients with severe RDEB. Stem Cells Translational Medicine 2018;7:530–542