Characterization of hematopoietic stem cell-derived microglia-like cells in nonhuman primates.

Authors

Nicholas E Petty, Carl B Wolf, Greta Kanestrom, Mark Mendoza, Kyle Swing, Robert D Murnane, Alvin Tong, Marlena Starrs, Emily Fields, Ravishankar Madhu, Veronica Nelson, Frederick C Bennett, Scott N Furlan, Keith R Loeb, Stefan Radtke, Hans-Peter Kiem

Published in

Blood advances. Jun 18, 2026. Epub Jun 18, 2026.

Abstract

Hematopoietic stem cell transplantation (HSCT) is the current standard of care for a number of neurotrophic lysosomal storage disorders. The therapeutic mechanism of HSCT is believed to be mediated by engraftment of HSC progeny to the brain as microglia-like cells (MLCs). However, the engraftment of MLCs and their transcriptomic identity relative to endogenous microglia is poorly understood. Here, we utilize the autologous nonhuman primate (NHP) HSCT model to investigate the engraftment of MLCs after gene-modified autologous HSCT. We observed engraftment of gene-marked MLCs across a cohort of five NHPs. MLCs engrafted through diverse brain regions; adopted a homeostatic, ramified morphology, and upregulated core microglial transcripts. We then utilized single cell RNA sequencing to more rigorously evaluate the transcriptome of MLCs, revealing a border-associated macrophage-like phenotype. Our findings offer critical insights into the engraftment and behavior of MLCs post-HSCT, laying the groundwork for their future utilization as a directed therapeutic.

PMID:
42314036
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.