In vitro biomimetic engineering of a human hematopoietic niche with functional properties
Bourgine, Paul LU
; Klein, Thibaut
; Paczulla, Anna M.
; Shimizu, Takafumi
; Kunz, Leo
; Kokkaliaris, Konstantinos D.
; Coutu, Daniel L.
; Lengerke, Claudia
; Skoda, Radek C.
and Schroeder, Timm
, et al.
(2018)
In Proceedings of the National Academy of Sciences
115(25).
p.5688-5695
- Abstract
- In adults, human hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment. Our understanding of human hematopoiesis and the associated niche biology remains limited, due to human material accessibility and limits of existing in vitro culture models. The establishment of an in vitro BM system would offer an experimentally accessible and tunable platform to study human hematopoiesis. Here, we develop a 3D engineered human BM analog by recapitulating some of the hematopoietic niche elements. This includes a bone-like scaffold, functionalized by human stromal and osteoblastic cells and by the extracellular matrix they deposited during perfusion culture in bioreactors. The resulting tissue exhibited... (More)
- In adults, human hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment. Our understanding of human hematopoiesis and the associated niche biology remains limited, due to human material accessibility and limits of existing in vitro culture models. The establishment of an in vitro BM system would offer an experimentally accessible and tunable platform to study human hematopoiesis. Here, we develop a 3D engineered human BM analog by recapitulating some of the hematopoietic niche elements. This includes a bone-like scaffold, functionalized by human stromal and osteoblastic cells and by the extracellular matrix they deposited during perfusion culture in bioreactors. The resulting tissue exhibited compositional and structural features of human BM while supporting the maintenance of HSPCs. This was associated with a compartmentalization of phenotypes in the bioreactor system, where committed blood cells are released into the liquid phase and HSPCs preferentially reside within the engineered BM tissue, establishing physical interactions with the stromal compartment. Finally, we demonstrate the possibility to perturb HSPCs’ behavior within our 3D niches by molecular customization or injury simulation. The developed system enables the design of advanced, tunable in vitro BM proxies for the study of human hematopoiesis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/ad177731-c535-491d-aa82-2a3de59d22e8
- author
- Bourgine, Paul
LU
; Klein, Thibaut
; Paczulla, Anna M.
; Shimizu, Takafumi
; Kunz, Leo
; Kokkaliaris, Konstantinos D.
; Coutu, Daniel L.
; Lengerke, Claudia
; Skoda, Radek C.
and Schroeder, Timm
, et al. (More)
- Bourgine, Paul
LU
; Klein, Thibaut
; Paczulla, Anna M.
; Shimizu, Takafumi
; Kunz, Leo
; Kokkaliaris, Konstantinos D.
; Coutu, Daniel L.
; Lengerke, Claudia
; Skoda, Radek C.
; Schroeder, Timm
and Martin, Ivan
(Less)
- publishing date
- 2018-06-19
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 115
- issue
- 25
- pages
- 8 pages
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:85048931920
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1805440115
- language
- English
- LU publication?
- no
- id
- ad177731-c535-491d-aa82-2a3de59d22e8
- date added to LUP
- 2022-02-09 18:58:35
- date last changed
- 2022-04-12 08:14:27
@article{ad177731-c535-491d-aa82-2a3de59d22e8,
abstract = {{In adults, human hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment. Our understanding of human hematopoiesis and the associated niche biology remains limited, due to human material accessibility and limits of existing in vitro culture models. The establishment of an in vitro BM system would offer an experimentally accessible and tunable platform to study human hematopoiesis. Here, we develop a 3D engineered human BM analog by recapitulating some of the hematopoietic niche elements. This includes a bone-like scaffold, functionalized by human stromal and osteoblastic cells and by the extracellular matrix they deposited during perfusion culture in bioreactors. The resulting tissue exhibited compositional and structural features of human BM while supporting the maintenance of HSPCs. This was associated with a compartmentalization of phenotypes in the bioreactor system, where committed blood cells are released into the liquid phase and HSPCs preferentially reside within the engineered BM tissue, establishing physical interactions with the stromal compartment. Finally, we demonstrate the possibility to perturb HSPCs’ behavior within our 3D niches by molecular customization or injury simulation. The developed system enables the design of advanced, tunable in vitro BM proxies for the study of human hematopoiesis.}},
author = {{Bourgine, Paul and Klein, Thibaut and Paczulla, Anna M. and Shimizu, Takafumi and Kunz, Leo and Kokkaliaris, Konstantinos D. and Coutu, Daniel L. and Lengerke, Claudia and Skoda, Radek C. and Schroeder, Timm and Martin, Ivan}},
issn = {{1091-6490}},
language = {{eng}},
month = {{06}},
number = {{25}},
pages = {{5688--5695}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{In vitro biomimetic engineering of a human hematopoietic niche with functional properties}},
url = {{http://dx.doi.org/10.1073/pnas.1805440115}},
doi = {{10.1073/pnas.1805440115}},
volume = {{115}},
year = {{2018}},
}