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Human Chorionic Stem Cells: Podocyte Differentiation and Potential for the Treatment of Alport Syndrome

Moschidou, D; Corcelli, M; Hau, K-L; Ekwalla, VJ; Behmoaras, JV; De Coppi, P; David, AL; ... Guillot, PV; + view all (2016) Human Chorionic Stem Cells: Podocyte Differentiation and Potential for the Treatment of Alport Syndrome. Stem Cells and Development , 25 (5) pp. 395-404. 10.1089/scd.2015.0305. Green open access

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Abstract

Alport syndrome (AS) is a hereditary glomerulopathy caused by a mutation in type IV collagen genes, which disrupts glomerular basement membrane, leading to progressive glomerulosclerosis and end-stage renal failure. There is at present no cure for AS, and cell-based therapies offer promise to improve renal function. In this study, we found that human first trimester fetal chorionic stem cells (CSC) are able to migrate to glomeruli and differentiate down the podocyte lineage in vitro and in vivo. When transplanted into 7-week-old Alport 129Sv-Col4α3tm1Dec/J (−/−) mice, a single intraperitoneal injection of CSC significantly lowered blood urea and urine proteinuria levels over the ensuing 2 weeks. In addition, nearly two-thirds of transplanted −/− mice maintained their weight above the 80% welfare threshold, with both males and females weighing more than age-matched nontransplanted −/− mice. This was associated with less renal cortical fibrosis and interstitial inflammation compared to nontransplanted mice as shown by reduction in murine CD4, CD68, and CD45.2 cells. Transplanted CSC homed to glomeruli, where they expressed CR1, VEGFA, SYNAPTOPODIN, CD2AP, and PODOCIN at the RNA level and produced PODOCIN, CD2AP, and COLIVα3 proteins in nontransplanted −/− mice, indicating that CSC have adopted a podocyte phenotype. Together, these data indicate that CSC may be used to delay progression of renal pathology by a combination of anti-inflammatory effects and replacement of the defective resident podocytes.

Type: Article
Title: Human Chorionic Stem Cells: Podocyte Differentiation and Potential for the Treatment of Alport Syndrome
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/scd.2015.0305
Publisher version: http://dx.doi.org/10.1089/scd.2015.0305
Language: English
Additional information: Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/scd.2015.0305.
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell & Tissue Engineering, Hematology, Medicine, Research & Experimental, Transplantation, Cell Biology, Research & Experimental Medicine, Mouse Model, Kidney-Disease, Renal-Disease, Mice, Progression, Defects, Bone, Transplantation, Regeneration, Fibrosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1483727
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