A single epidermal stem cell strategy for safe ex vivo gene therapy

EMBO Molecular Medicine
Stéphanie Droz-Georget LathionYann Barrandon

Abstract

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by dete...Continue Reading

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Citations

Sep 24, 2015·The Journal of Investigative Dermatology·Christos GeorgiadisWaseem Qasim
Sep 22, 2016·Stem Cells and Development·Parvaneh MohammadiNasser Aghdami
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Apr 3, 2021·The European Respiratory Journal·Dani Do Hyang LeeChristopher O'Callaghan

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Datasets Mentioned

BETA
SRP050326

Methods Mentioned

BETA
biopsy
PCR
Fluorescence
biopsies
fluorescence-activated cell sorting
FCS
electron microscopy
PCRs

Software Mentioned

LifeScope

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