Efficacy of Human Placental-Derived Stem Cells in Collagen VII Knockout (Recessive Dystrophic Epidermolysis Bullosa) Animal Model

Abstract

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

Cord Blood-Derived Stem Cells Suppress Fibrosis and May Prevent Malignant Progression in Recessive Dystrophic Epidermolysis Bullosa

“…We recently showed that repeated injection of dextran/human serum albumin (D/HSA) buffer were able to extend the survival of some col7a1 −/− mice, most likely by adjusting fluid balance, although it had no significant effect on the median life span . The mice that survived enabled the current investigation on the dynamic development of TGFβ signaling in this animal model.…”

Innovations in Human Stem Cell Research: A Holy Grail for Regenerative Medicine

“…Recently Celgene Cellular Therapeutics, Inc. manufactured human placental-derived stem cells (HPDSCs) from full-term donor placentas following saline perfusion, red blood cell depletion, and volume reduction. The overall cell types as determined by flow cytometry analysis are similar between HPDSCs and CB [127]. However, HPDSCs contain a significantly higher level of both hematopoietic and non-hematopoietic stem and progenitor cells than CB.…”

“…A pilot clinical study demonstrated that adding HPDSCs as universal donor cells with CB transplantation in patients with malignant and nonmalignant diseases had no adverse effects and may reduce the incidence of aGvHD [128]. Administration of HPDSCs in a mouse model of RDEB, in the absence of any conditioning regimen, also resulted in significant improvement on the survival and disease manifestation of the recipient mice [127]. [125].…”

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“…21 In a subsequent STEM CELLS Translational Medicine article, Liao et al explored the potential direct regenerative properties of HPDSCs by evaluating their efficacy in a mouse model of RDEB. 12 The authors demonstrated that a single intrahepatic administration of HPDSCs in the absence of any preconditioning or immunosuppression significantly increased the median life span of RDEB model mice (from 2 to 7 days) and alleviated hemorrhagic blistering. Encouragingly, an additional HPDSC administration further extended the median life span to 18 days.…”