Donor cell engineering with GSK3 inhibitor–loaded nanoparticles enhances engraftment after in utero transplantation

Stavros P. Loukogeorgakis, Camila G. Fachin, Andre I.B.S. Dias, Haiying Li, Li Tang, Aimee G. Kim, Jesse D. Vrecenak, John D. Stratigis, Nicholas J. Ahn, Ilana Nissim, Izhtak Nissim, Antonio F. Moron, Jose L. Martins, William H. Peranteau, Paolo de Coppi, Darrell J. Irvine, Alan W. Flake

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)1983-1995
Number of pages13
JournalBlood
Volume134
Issue number22
DOIs
StatePublished - 2019

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