Culturing patient-derived malignant hematopoietic stem cells in engineered and fully humanized 3D niches.

Autor:	García-García A; Tissue Engineering, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland; andres.garcia-garcia@unibas.ch ivan.martin@usb.ch., Klein T; Tissue Engineering, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland., Born G; Tissue Engineering, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.; Technologies for Tissue Engineering, Department of Biomedical Engineering, University of Basel, 4123 Allschwil, Switzerland., Hilpert M; Tissue Engineering, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland., Scherberich A; Tissue Engineering, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.; Technologies for Tissue Engineering, Department of Biomedical Engineering, University of Basel, 4123 Allschwil, Switzerland., Lengerke C; Stem Cells and Hematopoiesis, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland., Skoda RC; Experimental Hematology, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland., Bourgine PE; Laboratory for Cell, Tissue, and Organ Engineering, Department of Clinical Sciences, Wallenberg Center for Molecular Medicine, Lund University, 22100 Lund, Sweden.; Stem Cell Center, Lund University, 221 00 Lund, Sweden., Martin I; Tissue Engineering, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland; andres.garcia-garcia@unibas.ch ivan.martin@usb.ch.; Technologies for Tissue Engineering, Department of Biomedical Engineering, University of Basel, 4123 Allschwil, Switzerland.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Oct 05; Vol. 118 (40).
DOI:	10.1073/pnas.2114227118
Abstrakt:	Human malignant hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) niches, which remain challenging to explore due to limited in vivo accessibility and constraints with humanized animal models. Several in vitro systems have been established to culture patient-derived HSPCs in specific microenvironments, but they do not fully recapitulate the complex features of native bone marrow. Our group previously reported that human osteoblastic BM niches (O-N), engineered by culturing mesenchymal stromal cells within three-dimensional (3D) porous scaffolds under perfusion flow in a bioreactor system, are capable of maintaining, expanding, and functionally regulating healthy human cord blood-derived HSPCs. Here, we first demonstrate that this 3D O-N can sustain malignant CD34 + cells from acute myeloid leukemia (AML) and myeloproliferative neoplasm patients for up to 3 wk. Human malignant cells distributed in the bioreactor system mimicking the spatial distribution found in native BM tissue, where most HSPCs remain linked to the niches and mature cells are released to the circulation. Using human adipose tissue-derived stromal vascular fraction cells, we then generated a stromal-vascular niche and demonstrated that O-N and stromal-vascular niche differentially regulate leukemic UCSD-AML1 cell expansion, immunophenotype, and response to chemotherapy. The developed system offers a unique platform to investigate human leukemogenesis and response to drugs in customized environments, mimicking defined features of native hematopoietic niches and compatible with the establishment of personalized settings. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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