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.

A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies / 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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019), pp. 366.1-366.14. [10.1038/s41467-018-08166-x]

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

Tebaldi, Toma;
2019-01-01

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.
2019
1
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
A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies / 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. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019), pp. 366.1-366.14. [10.1038/s41467-018-08166-x]
File in questo prodotto:
File Dimensione Formato  
2019_Song_Nat_Commun.pdf

accesso aperto

Tipologia: Versione editoriale (Publisher’s layout)
Licenza: Creative commons
Dimensione 3.16 MB
Formato Adobe PDF
3.16 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/328052
Citazioni
  • ???jsp.display-item.citation.pmc??? 26
  • Scopus 60
  • ???jsp.display-item.citation.isi??? 60
social impact