Ectopic human mesenchymal stem cell-coated scaffolds in NOD/SCID mice: an in vivo model of the leukemia niche.
Human mesenchymal stem cells form the supportive structure in which the functional cells of a differentiated tissue reside. We describe the creation of ectopic niches within polyurethane scaffolds coated with human mesenchymal stem cells. When implanted subcutaneously in NOD/SCID mice, these niches supported engraftment of primary human acute myeloid leukemia cells. The scaffolds showed vascularization and presence of osteoclasts and adipocytes, suggestive of an organizing human bone marrow microenvironment in the murine host. The chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are critical for homing and migration of acute myeloid leukemia. We found that a CXCR4 antagonist could disrupt homing to the ectopic niches, possibly by modulation of the mesenchymal stroma. We believe that these scaffold niches provide a new and powerful tool to study the leukemia stem cell microenvironment and may be useful for identification of novel drug targets.
Vaiselbuh
Sarah R
SR
Department of Pediatric Hemato/Oncology, Cohen Children's Medical Center, New Hyde Park, New York, USA. smeeus@nshs.edu
Edelman
Morris
M
Lipton
Jeffrey M
JM
Liu
Johnson M
JM
D000818:Animals; D002478:Cells, Cultured; D002828:Choristoma / Q000473:pathology*; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000473:pathology; D055153:Stem Cell Niche / Q000166:cytology / Q000473:pathology*; D054457:Tissue Scaffolds / Q000737:chemistry; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000502:physiology
D020099:Coated Materials, Biocompatible