Ectopic Humanized Mesenchymal Niche in Mice Enables Robust Engraftment of Myelodysplastic Stem Cells

Overview

Journal Blood Cancer Discov

Specialties Hematology
Oncology

Date 2021 Mar 29

PMID 33778768

Citations 14

Authors

Syed A Mian

Ander Abarrategi

Kar Lok Kong

Kevin Rouault-Pierre

Henry Wood

Caroline A Oedekoven

Alexander E Smith

Antoniana Batsivari

Linda Ariza-McNaughton

Peter Johnson

Thomas Snoeks

Ghulam J Mufti

Dominique Bonnet

Affiliations

Soon will be listed here.

Abstract

Myelodysplastic syndrome (MDS) are clonal stem cell diseases characterized mainly by ineffective hematopoiesis. Here, we present an approach that enables robust long-term engraftment of primary MDS stem cells (MDS-SCs) in mice by implantation of human mesenchymal cell-seeded scaffolds. Critically for modelling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 10 CD34 cells can be engrafted and expanded by this approach with the maintenance of the genetic make-up seen in the patients. Non-invasive high-resolution ultrasound imaging shows that these scaffolds are fully perfused. Our data shows that human microenvironment but not mouse is essential to MDS-SCs homing and engraftment. Notably, the alternative niche provided by healthy donor MSCs enhanced engraftment of MDS-SCs. This study characterizes a new tool to model MDS human disease with the level of engraftment previously unattainable in mice, and offers insights into human-specific determinants of MDS-SC microenvironment.

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