A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies

Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient “MISTRG” mice that pro...

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Published inNature communications Vol. 10; no. 1; pp. 366 - 14
Main Authors Song, Yuanbin, Rongvaux, Anthony, Taylor, Ashley, Jiang, Tingting, Tebaldi, Toma, Balasubramanian, Kunthavai, Bagale, Arun, Terzi, Yunus Kasim, Gbyli, Rana, Wang, Xiaman, Fu, Xiaoying, Gao, Yimeng, Zhao, Jun, Podoltsev, Nikolai, Xu, Mina, Neparidze, Natalia, Wong, Ellice, Torres, Richard, Bruscia, Emanuela M., Kluger, Yuval, Manz, Markus G., Flavell, Richard A., Halene, Stephanie
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 21.01.2019
Nature Publishing Group
Nature Portfolio
Subjects
13/100
13/31
45
45/23
631/67/71
64/110
64/60
692/699/1541/1990/1673
Animals
Antigens, CD - genetics
Antigens, CD - immunology
Biomarkers - metabolism
Bone marrow
Catalysis
Chemical properties
Cytokines - genetics
Cytokines - immunology
Disease Models, Animal
DNA repair
Efficiency
Fuel cells
Gene Expression
Gene Knock-In Techniques
Genomics
Graft Survival
Hematology
Hematopoietic Stem Cell Transplantation - methods
Hematopoietic Stem Cells - immunology
Hematopoietic Stem Cells - pathology
Hospitals
Humanities and Social Sciences
Humans
Immunology
Laboratories
Medical research
Medicine
Mice
Mice, Transgenic
multidisciplinary
Myelodysplastic Syndromes - immunology
Myelodysplastic Syndromes - pathology
Oxides
Patients
Science
Science (multidisciplinary)
Stem Cell Niche - immunology
Stem cells
Transplantation, Heterologous
Xenografts
Online AccessGet full text

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Abstract Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient “MISTRG” mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients’ dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample’s genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research. Myelodyplastic hematopoietic stem cells (MDS HSC) have eluded in vivo modeling. Here the authors present a highly efficient MDS patient-derived xenotransplantation model in cytokine-humanized mice with replication of the donors’ genetic complexity and myeloid, erythroid, and megakaryocytic lineage dysplasia.
AbstractList Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient “MISTRG” mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients’ dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample’s genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research. Myelodyplastic hematopoietic stem cells (MDS HSC) have eluded in vivo modeling. Here the authors present a highly efficient MDS patient-derived xenotransplantation model in cytokine-humanized mice with replication of the donors’ genetic complexity and myeloid, erythroid, and megakaryocytic lineage dysplasia.
Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient “MISTRG” mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients’ dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample’s genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.
Myelodyplastic hematopoietic stem cells (MDS HSC) have eluded in vivo modeling. Here the authors present a highly efficient MDS patient-derived xenotransplantation model in cytokine-humanized mice with replication of the donors’ genetic complexity and myeloid, erythroid, and megakaryocytic lineage dysplasia.
Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient “MISTRG” mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients’ dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample’s genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.Myelodyplastic hematopoietic stem cells (MDS HSC) have eluded in vivo modeling. Here the authors present a highly efficient MDS patient-derived xenotransplantation model in cytokine-humanized mice with replication of the donors’ genetic complexity and myeloid, erythroid, and megakaryocytic lineage dysplasia.
Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.
ArticleNumber 366
Author Song, Yuanbin
Balasubramanian, Kunthavai
Flavell, Richard A.
Kluger, Yuval
Gao, Yimeng
Bagale, Arun
Manz, Markus G.
Neparidze, Natalia
Podoltsev, Nikolai
Bruscia, Emanuela M.
Jiang, Tingting
Tebaldi, Toma
Torres, Richard
Wong, Ellice
Rongvaux, Anthony
Wang, Xiaman
Zhao, Jun
Halene, Stephanie
Terzi, Yunus Kasim
Taylor, Ashley
Fu, Xiaoying
Xu, Mina
Gbyli, Rana
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  organization: Section of Hematology, Department of Internal Medicine and Yale Comprehensive Cancer Center, Yale University School of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30664659$$D View this record in MEDLINE/PubMed
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Snippet Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current...
Myelodyplastic hematopoietic stem cells (MDS HSC) have eluded in vivo modeling. Here the authors present a highly efficient MDS patient-derived...
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StartPage 366
SubjectTerms 13/100
13/31
45
45/23
631/67/71
64/110
64/60
692/699/1541/1990/1673
Animals
Antigens, CD - genetics
Antigens, CD - immunology
Biomarkers - metabolism
Bone marrow
Catalysis
Chemical properties
Cytokines - genetics
Cytokines - immunology
Disease Models, Animal
DNA repair
Efficiency
Fuel cells
Gene Expression
Gene Knock-In Techniques
Genomics
Graft Survival
Hematology
Hematopoietic Stem Cell Transplantation - methods
Hematopoietic Stem Cells - immunology
Hematopoietic Stem Cells - pathology
Hospitals
Humanities and Social Sciences
Humans
Immunology
Laboratories
Medical research
Medicine
Mice
Mice, Transgenic
multidisciplinary
Myelodysplastic Syndromes - immunology
Myelodysplastic Syndromes - pathology
Oxides
Patients
Science
Science (multidisciplinary)
Stem Cell Niche - immunology
Stem cells
Transplantation, Heterologous
Xenografts
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Title A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies
URI https://link.springer.com/article/10.1038/s41467-018-08166-x
https://www.ncbi.nlm.nih.gov/pubmed/30664659
https://www.proquest.com/docview/1915326860
https://www.proquest.com/docview/2179426370
https://pubmed.ncbi.nlm.nih.gov/PMC6341122
https://doaj.org/article/bcd8edb0cae9459b894b2cf494c1bf39
Volume 10
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