Loukogeorgakis, SP;
Fachin, CG;
Santos Dias, A;
Li, H;
Tang, L;
Kim, AG;
Vrecenak, JD;
... Flake, AW; + view all
(2019)
Donor cell engineering with GSK3 inhibitor–loaded nanoparticles enhances engraftment after in utero transplantation.
Blood
, 134
(22)
pp. 1983-1995.
10.1182/blood.2019001037.
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Abstract
Host cell competition is a major barrier to engraftment after in utero hematopoietic cell transplantation (IUHCT). Here we describe a cell-engineering strategy using glycogen synthase kinase-3 (GSK3) inhibitor–loaded nanoparticles conjugated to the surface of donor hematopoietic cells to enhance their proliferation kinetics and ability to compete against their fetal host equivalents. With this approach, we achieved remarkable levels of stable, long-term hematopoietic engraftment for up to 24 weeks post-IUHCT. We also show that the salutary effects of the nanoparticle-released GSK3 inhibitor are specific to donor progenitor/stem cells and achieved by a pseudoautocrine mechanism. These results establish that IUHCT of hematopoietic cells decorated with GSK3 inhibitor–loaded nanoparticles can produce therapeutic levels of long-term engraftment and could therefore allow single-step prenatal treatment of congenital hematological disorders.
| Type: | Article |
|---|---|
| Title: | Donor cell engineering with GSK3 inhibitor–loaded nanoparticles enhances engraftment after in utero transplantation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1182/blood.2019001037 |
| Publisher version: | https://doi.org/10.1182/blood.2019001037 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | donors, engineering, engraftment, glycogen synthase kinase 3, hematological diseases, nanoparticles, transplantation, hematopoietic stem cell transplantation, prenatal care, host (organism) |
| UCL classification: | UCL 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 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-pp.ucl.ac.uk/id/eprint/10086553 |
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