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Engineered humanized bone organs maintain human hematopoiesis in vivo

Fritsch, Kristin ; Pigeot, Sébastien ; Feng, Xiaomin ; Bourgine, Paul E. LU orcid ; Schroeder, Timm ; Martin, Ivan ; Manz, Markus G. and Takizawa, Hitoshi (2018) In Experimental Hematology 61. p.5-51
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... (More)
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. (Less)
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author
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publishing date
type
Contribution to journal
publication status
published
in
Experimental Hematology
volume
61
pages
5 - 51
publisher
Elsevier
external identifiers
  • scopus:85042403420
ISSN
1873-2399
DOI
10.1016/j.exphem.2018.01.004
language
English
LU publication?
no
id
05d366f3-5124-43e6-9dc0-f35edce8afa5
date added to LUP
2022-02-09 18:59:55
date last changed
2022-04-28 00:05:36
@article{05d366f3-5124-43e6-9dc0-f35edce8afa5,
  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.}},
  author       = {{Fritsch, Kristin and Pigeot, Sébastien and Feng, Xiaomin and Bourgine, Paul E. and Schroeder, Timm and Martin, Ivan and Manz, Markus G. and Takizawa, Hitoshi}},
  issn         = {{1873-2399}},
  language     = {{eng}},
  pages        = {{5--51}},
  publisher    = {{Elsevier}},
  series       = {{Experimental Hematology}},
  title        = {{Engineered humanized bone organs maintain human hematopoiesis in vivo}},
  url          = {{http://dx.doi.org/10.1016/j.exphem.2018.01.004}},
  doi          = {{10.1016/j.exphem.2018.01.004}},
  volume       = {{61}},
  year         = {{2018}},
}