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Engineered humanized bone organs maintain human hematopoiesis in vivo


Fritsch, Kristin; Pigeot, Sébastien; Feng, Xiaomin; Bourgine, Paul E; Schroeder, Timm; Martin, Ivan; Manz, Markus G; Takizawa, Hitoshi (2018). Engineered humanized bone organs maintain human hematopoiesis in vivo. Experimental Hematology, 61:45-51.e5.

Abstract

Hematopoietic stem cells (HSCs) are maintained in a specialized bone marrow (BM) environment, the so-called HSC niche, that provides pivotal factors for their maintenance. Although the cellular and molecular components of the mouse BM HSC niche have been extensively studied using genetically modified animals, relatively little is known about the counterpart human BM niche components. We previously illustrated, with a developmental tissue engineering approach, that human adult BM-derived mesenchymal stromal cells (MSCs) can develop into human bone organs (so-called ossicles) through endochondral ossification in vivo and that these human ossicles are able to maintain functional mouse HSCs. We here report that human ossicles in immunodeficient mice maintain human immature and mature hematopoiesis in vivo. Moreover, a higher percentage of human stem and progenitor cells are kept in quiescence in human ossicles as compared with mouse BM. These findings indicate that the human MSC-derived ossicles function as a hematopoietic niche and may potentially serve as a re-engineerable platform to study normal and diseased human hematopoiesis in a physiologically optimized environment.

Abstract

Hematopoietic stem cells (HSCs) are maintained in a specialized bone marrow (BM) environment, the so-called HSC niche, that provides pivotal factors for their maintenance. Although the cellular and molecular components of the mouse BM HSC niche have been extensively studied using genetically modified animals, relatively little is known about the counterpart human BM niche components. We previously illustrated, with a developmental tissue engineering approach, that human adult BM-derived mesenchymal stromal cells (MSCs) can develop into human bone organs (so-called ossicles) through endochondral ossification in vivo and that these human ossicles are able to maintain functional mouse HSCs. We here report that human ossicles in immunodeficient mice maintain human immature and mature hematopoiesis in vivo. Moreover, a higher percentage of human stem and progenitor cells are kept in quiescence in human ossicles as compared with mouse BM. These findings indicate that the human MSC-derived ossicles function as a hematopoietic niche and may potentially serve as a re-engineerable platform to study normal and diseased human hematopoiesis in a physiologically optimized environment.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology and Hematology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Molecular Biology
Health Sciences > Hematology
Life Sciences > Genetics
Life Sciences > Cell Biology
Life Sciences > Cancer Research
Uncontrolled Keywords:Genetics, Cell Biology, Cancer Research, Molecular Biology, Hematology
Language:English
Date:May 2018
Deposited On:08 May 2018 15:49
Last Modified:29 Jul 2020 07:12
Publisher:Elsevier
ISSN:0301-472X
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.exphem.2018.01.004
PubMed ID:29410245

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