TY - JOUR
T1 - Reconstructing the human hematopoietic niche in immunodeficient mice
T2 - opportunities for studying primary multiple myeloma
AU - Groen, Richard W J
AU - Noort, Willy A
AU - Raymakers, Reinier A
AU - Prins, Henk-Jan
AU - Aalders, Linda
AU - Hofhuis, Frans M
AU - Moerer, Petra
AU - van Velzen, Jeroen F
AU - Bloem, Andries C
AU - van Kessel, Berris
AU - Rozemuller, Henk
AU - van Binsbergen, Ellen
AU - Buijs, Arjan
AU - Yuan, Huipin
AU - de Bruijn, Joost D
AU - de Weers, Michel
AU - Parren, Paul W H I
AU - Schuringa, Jan Jacob
AU - Lokhorst, Henk M
AU - Mutis, Tuna
AU - Martens, Anton C M
PY - 2012/7/19
Y1 - 2012/7/19
N2 - Interactions within the hematopoietic niche in the BM microenvironment are essential for maintenance of the stem cell pool. In addition, this niche is thought to serve as a sanctuary site for malignant progenitors during chemotherapy. Therapy resistance induced by interactions with the BM microenvironment is a major drawback in the treatment of hematologic malignancies and bone-metastasizing solid tumors. To date, studying these interactions was hampered by the lack of adequate in vivo models that simulate the human situation. In the present study, we describe a unique human-mouse hybrid model that allows engraftment and outgrowth of normal and malignant hematopoietic progenitors by implementing a technology for generating a human bone environment. Using luciferase gene marking of patient-derived multiple myeloma cells and bioluminescent imaging, we were able to follow pMM cells outgrowth and to visualize the effect of treatment. Therapeutic interventions in this model resulted in equivalent drug responses as observed in the corresponding patients. This novel human-mouse hybrid model creates unprecedented opportunities to investigate species-specific microenvironmental influences on normal and malignant hematopoietic development, and to develop and personalize cancer treatment strategies.
AB - Interactions within the hematopoietic niche in the BM microenvironment are essential for maintenance of the stem cell pool. In addition, this niche is thought to serve as a sanctuary site for malignant progenitors during chemotherapy. Therapy resistance induced by interactions with the BM microenvironment is a major drawback in the treatment of hematologic malignancies and bone-metastasizing solid tumors. To date, studying these interactions was hampered by the lack of adequate in vivo models that simulate the human situation. In the present study, we describe a unique human-mouse hybrid model that allows engraftment and outgrowth of normal and malignant hematopoietic progenitors by implementing a technology for generating a human bone environment. Using luciferase gene marking of patient-derived multiple myeloma cells and bioluminescent imaging, we were able to follow pMM cells outgrowth and to visualize the effect of treatment. Therapeutic interventions in this model resulted in equivalent drug responses as observed in the corresponding patients. This novel human-mouse hybrid model creates unprecedented opportunities to investigate species-specific microenvironmental influences on normal and malignant hematopoietic development, and to develop and personalize cancer treatment strategies.
KW - Animals
KW - DNA-Binding Proteins/genetics
KW - Disease Models, Animal
KW - Ear Ossicles/cytology
KW - Hematopoietic Stem Cell Transplantation/methods
KW - Hematopoietic Stem Cells/cytology
KW - Humans
KW - Immunologic Deficiency Syndromes/genetics
KW - Mice
KW - Mice, Mutant Strains
KW - Multiple Myeloma/immunology
KW - Neoplasm Transplantation
KW - Osteolysis/immunology
KW - Stem Cell Niche/immunology
KW - Tissue Scaffolds
KW - Transplantation Chimera/immunology
KW - Transplantation, Heterologous
KW - Tumor Microenvironment/immunology
U2 - https://doi.org/10.1182/blood-2012-03-414920
DO - https://doi.org/10.1182/blood-2012-03-414920
M3 - Article
C2 - 22653974
SN - 0006-4971
VL - 120
SP - e9-e16
JO - Blood
JF - Blood
IS - 3
ER -