Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis.

Details

Serval ID
serval:BIB_C4E7399073B7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis.
Journal
Biomaterials
Author(s)
Tavakol D.N., Tratwal J., Bonini F., Genta M., Campos V., Burch P., Hoehnel S., Béduer A., Alessandrini M., Naveiras O., Braschler T.
ISSN
1878-5905 (Electronic)
ISSN-L
0142-9612
Publication state
Published
Issued date
02/2020
Peer-reviewed
Oui
Volume
232
Pages
119665
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Modeling the interaction between the supportive stroma and the hematopoietic stem and progenitor cells (HSPC) is of high interest in the regeneration of the bone marrow niche in blood disorders. In this work, we present an injectable co-culture system to study this interaction in a coherent in vitro culture and in vivo transplantation model. We assemble a 3D hematopoietic niche in vitro by co-culture of supportive OP9 mesenchymal cells and HSPCs in porous, chemically defined collagen-coated carboxymethylcellulose microscaffolds (CCMs). Flow cytometry and hematopoietic colony forming assays demonstrate the stromal supportive capacity for in vitro hematopoiesis in the absence of exogenous cytokines. After in vitro culture, we recover a paste-like living injectable niche biomaterial from CCM co-cultures by controlled, partial dehydration. Cell viability and the association between stroma and HSPCs are maintained in this process. After subcutaneous injection of this living artificial niche in vivo, we find maintenance of stromal and hematopoietic populations over 12 weeks in immunodeficient mice. Indeed, vascularization is enhanced in the presence of HSPCs. Our approach provides a minimalistic, scalable, biomimetic in vitro model of hematopoiesis in a microcarrier format that preserves the HSPC progenitor function, while being injectable in vivo without disrupting the cell-cell interactions established in vitro.
Keywords
Bone marrow niche, Extramedullary hematopoiesis, Hematopoietic stem cells, Minimally invasive, Scaffold, Stroma
Pubmed
Web of science
Create date
03/01/2020 22:43
Last modification date
08/12/2020 7:24
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