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

Publié dansBiomaterials, vol. 232, 119665
Date de publication2020
Résumé

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.

Mots-clés
  • Bone marrow niche
  • Minimally invasive
  • Stroma
  • Hematopoietic stem cells
  • Extramedullary Hematopoiesis
  • Scaffold
Citation (format ISO)
TAVAKOL, Daniel Naveed et al. Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis. In: Biomaterials, 2020, vol. 232, p. 119665. doi: 10.1016/j.biomaterials.2019.119665
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Article (Accepted version)
Identifiants
ISSN du journal0142-9612
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Informations techniques

Création11.11.2020 13:40:00
Première validation11.11.2020 13:40:00
Heure de mise à jour15.03.2023 23:23:09
Changement de statut15.03.2023 23:23:08
Dernière indexation12.02.2024 13:20:54
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