Reconstructing the human hematopoietic niche in immunodeficient mice: Opportunities for studying primary multiple myeloma

R.W.J. Groen, W.A. van Noort, R.A. Raymakers, H.J. Prins, L. Aalders, F.M. Hofhuis, P. Moerer, J.F. van Velzen, A.C. Bloem, B. van Kessel, H. Rozemuller, E. van Binsbergen, A. Buijs, Huipin Yuan, Joost Dick de Bruijn, M. de Weers, P.W.H.I. Parren, J.J. Schuringa, H.M. Lokhorst, T. Mutis & 1 others ACM Martens

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Abstract

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.
Original languageEnglish
Pages (from-to)e9-e16
JournalBlood
Volume120
Issue number3
DOIs
Publication statusPublished - 2012

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Multiple Myeloma
Bone
Oncology
Chemotherapy
Therapeutics
Bone and Bones
Stem cells
Luciferases
Tumors
Hematologic Neoplasms
Genes
Neoplasms
Imaging techniques
Stem Cells
Maintenance
Technology
Drug Therapy
Pharmaceutical Preparations

Keywords

  • METIS-288455
  • IR-81834

Cite this

Groen, R. W. J., van Noort, W. A., Raymakers, R. A., Prins, H. J., Aalders, L., Hofhuis, F. M., ... Martens, ACM. (2012). Reconstructing the human hematopoietic niche in immunodeficient mice: Opportunities for studying primary multiple myeloma. Blood, 120(3), e9-e16. https://doi.org/10.1182/blood-2012-03-414920
Groen, R.W.J. ; van Noort, W.A. ; Raymakers, R.A. ; Prins, H.J. ; Aalders, L. ; Hofhuis, F.M. ; Moerer, P. ; van Velzen, J.F. ; Bloem, A.C. ; van Kessel, B. ; Rozemuller, H. ; van Binsbergen, E. ; Buijs, A. ; Yuan, Huipin ; de Bruijn, Joost Dick ; de Weers, M. ; Parren, P.W.H.I. ; Schuringa, J.J. ; Lokhorst, H.M. ; Mutis, T. ; Martens, ACM. / Reconstructing the human hematopoietic niche in immunodeficient mice: Opportunities for studying primary multiple myeloma. In: Blood. 2012 ; Vol. 120, No. 3. pp. e9-e16.
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abstract = "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.",
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author = "R.W.J. Groen and {van Noort}, W.A. and R.A. Raymakers and H.J. Prins and L. Aalders and F.M. Hofhuis and P. Moerer and {van Velzen}, J.F. and A.C. Bloem and {van Kessel}, B. and H. Rozemuller and {van Binsbergen}, E. and A. Buijs and Huipin Yuan and {de Bruijn}, {Joost Dick} and {de Weers}, M. and P.W.H.I. Parren and J.J. Schuringa and H.M. Lokhorst and T. Mutis and ACM Martens",
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doi = "10.1182/blood-2012-03-414920",
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Groen, RWJ, van Noort, WA, Raymakers, RA, Prins, HJ, Aalders, L, Hofhuis, FM, Moerer, P, van Velzen, JF, Bloem, AC, van Kessel, B, Rozemuller, H, van Binsbergen, E, Buijs, A, Yuan, H, de Bruijn, JD, de Weers, M, Parren, PWHI, Schuringa, JJ, Lokhorst, HM, Mutis, T & Martens, ACM 2012, 'Reconstructing the human hematopoietic niche in immunodeficient mice: Opportunities for studying primary multiple myeloma' Blood, vol. 120, no. 3, pp. e9-e16. https://doi.org/10.1182/blood-2012-03-414920

Reconstructing the human hematopoietic niche in immunodeficient mice: Opportunities for studying primary multiple myeloma. / Groen, R.W.J.; van Noort, W.A.; Raymakers, R.A.; Prins, H.J.; Aalders, L.; Hofhuis, F.M.; Moerer, P.; van Velzen, J.F.; Bloem, A.C.; van Kessel, B.; Rozemuller, H.; van Binsbergen, E.; Buijs, A.; Yuan, Huipin; de Bruijn, Joost Dick; de Weers, M.; Parren, P.W.H.I.; Schuringa, J.J.; Lokhorst, H.M.; Mutis, T.; Martens, ACM.

In: Blood, Vol. 120, No. 3, 2012, p. e9-e16.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Reconstructing the human hematopoietic niche in immunodeficient mice: Opportunities for studying primary multiple myeloma

AU - Groen, R.W.J.

AU - van Noort, W.A.

AU - Raymakers, R.A.

AU - Prins, H.J.

AU - Aalders, L.

AU - Hofhuis, F.M.

AU - Moerer, P.

AU - van Velzen, J.F.

AU - Bloem, A.C.

AU - van Kessel, B.

AU - Rozemuller, H.

AU - van Binsbergen, E.

AU - Buijs, A.

AU - Yuan, Huipin

AU - de Bruijn, Joost Dick

AU - de Weers, M.

AU - Parren, P.W.H.I.

AU - Schuringa, J.J.

AU - Lokhorst, H.M.

AU - Mutis, T.

AU - Martens, ACM

PY - 2012

Y1 - 2012

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 - METIS-288455

KW - IR-81834

U2 - 10.1182/blood-2012-03-414920

DO - 10.1182/blood-2012-03-414920

M3 - Article

VL - 120

SP - e9-e16

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -