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2017 ; 8
(4
): 977-990
Nephropedia Template TP
gab.com Text
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Efficient Ex Vivo Engineering and Expansion of Highly Purified Human
Hematopoietic Stem and Progenitor Cell Populations for Gene Therapy
#MMPMID28330619
Zonari E
; Desantis G
; Petrillo C
; Boccalatte FE
; Lidonnici MR
; Kajaste-Rudnitski A
; Aiuti A
; Ferrari G
; Naldini L
; Gentner B
Stem Cell Reports
2017[Apr]; 8
(4
): 977-990
PMID28330619
show ga
Ex vivo gene therapy based on CD34(+) hematopoietic stem cells (HSCs) has shown
promising results in clinical trials, but genetic engineering to high levels and
in large scale remains challenging. We devised a sorting strategy that captures
more than 90% of HSC activity in less than 10% of mobilized peripheral blood
(mPB) CD34(+) cells, and modeled a transplantation protocol based on highly
purified, genetically engineered HSCs co-infused with uncultured progenitor
cells. Prostaglandin E(2) stimulation allowed near-complete transduction of HSCs
with lentiviral vectors during a culture time of less than 38 hr, mitigating the
negative impact of standard culture on progenitor cell function. Exploiting the
pyrimidoindole derivative UM171, we show that transduced mPB CD34(+)CD38(-) cells
with repopulating potential could be expanded ex vivo. Implementing these
findings in clinical gene therapy protocols will improve the efficacy, safety,
and sustainability of gene therapy and generate new opportunities in the field of
gene editing.