TY - JOUR
T1 - Ectopic Humanized Mesenchymal Niche in Mice Enables Robust Engraftment of Myelodysplastic Stem Cells
AU - Mian, Syed A.
AU - Abarrategi, Ander
AU - Kong, Kar Lok
AU - Rouault-Pierre, Kevin
AU - Wood, Henry
AU - Oedekoven, Caroline A.
AU - Smith, Alexander E.
AU - Batsivari, Antoniana
AU - Ariza-McNaughton, Linda
AU - Johnson, Peter
AU - Snoeks, Thomas
AU - Mufti, Ghulam J.
AU - Bonnet, Dominique
N1 - Publisher Copyright:
©2020 American Association for Cancer Research.
Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Myelodysplastic syndromes (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-SC) in mice by implantation of human mesenchymal cell-seeded scaffolds. Critically for modeling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 104 CD34+ cells can be engrafted and expanded by this approach with the maintenance of the genetic make-up seen in the patients. Noninvasive high-resolution ultrasound imaging shows that these scaffolds are fully perfused. Our data show that the human microenvironment but not mouse is essential to MDS-SC homing and engraftment. Notably, the alternative niche provided by healthy donor mesenchymal stromal cells enhances 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 the MDS-SC microenvironment. SIGNIFICANCE: These findings are significant for understanding the niche dependence of MDS. This report provides the evidence of the migratory behavior of hematopoietic stem cells in myeloid cancers. Our model offers a unique opportunity to study the clonal behavior of the myeloid/lymphoid cancers and delineate how cancer cells interact with different niches.
AB - Myelodysplastic syndromes (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-SC) in mice by implantation of human mesenchymal cell-seeded scaffolds. Critically for modeling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 104 CD34+ cells can be engrafted and expanded by this approach with the maintenance of the genetic make-up seen in the patients. Noninvasive high-resolution ultrasound imaging shows that these scaffolds are fully perfused. Our data show that the human microenvironment but not mouse is essential to MDS-SC homing and engraftment. Notably, the alternative niche provided by healthy donor mesenchymal stromal cells enhances 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 the MDS-SC microenvironment. SIGNIFICANCE: These findings are significant for understanding the niche dependence of MDS. This report provides the evidence of the migratory behavior of hematopoietic stem cells in myeloid cancers. Our model offers a unique opportunity to study the clonal behavior of the myeloid/lymphoid cancers and delineate how cancer cells interact with different niches.
UR - http://www.scopus.com/inward/record.url?scp=85111065175&partnerID=8YFLogxK
U2 - 10.1158/2643-3230.BCD-20-0161
DO - 10.1158/2643-3230.BCD-20-0161
M3 - Article
C2 - 34238759
AN - SCOPUS:85111065175
SN - 2159-8274
VL - 2
SP - 135
EP - 145
JO - Cancer discovery
JF - Cancer discovery
IS - 2
ER -