An engineered multicomponent bone marrow niche for the recapitulation of hematopoiesis at ectopic transplantation sites

Journal of Hematology & Oncology
Mónica S Ventura FerreiraRebekka K Schneider

Abstract

Bone marrow (BM) niches are often inaccessible for controlled experimentation due to their difficult accessibility, biological complexity, and three-dimensional (3D) geometry. Here, we report the development and characterization of a BM model comprising of cellular and structural components with increased potential for hematopoietic recapitulation at ectopic transplantation sites. Cellular components included mesenchymal stromal cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs). Structural components included 3D β-tricalcium phosphate (β-TCP) scaffolds complemented with Matrigel or collagen I/III gels for the recreation of the osteogenic/extracellular character of native BM. In vitro, β-TCP/Matrigel combinations robustly maintained proliferation, osteogenic differentiation, and matrix remodeling capacities of MSCs and maintenance of HSPCs function over time. In vivo, scaffolds promoted strong and robust recruitment of hematopoietic cells to sites of ectopic transplantation, vascularization, and soft tissue formation. Our tissue-engineered BM system is a powerful tool to explore the regulatory mechanisms of hematopoietic stem and progenitor cells for a better understanding of hematopoiesis in health and disease.

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Citations

May 10, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yu-Ru ShihShyni Varghese
Jan 4, 2017·Experimental Hematology & Oncology·Ningfei AnYubin Kang
Jun 24, 2017·American Journal of Hematology·Alexandre JanelMarc G Berger
Feb 7, 2018·Stem Cell Research & Therapy·Mónica S Ventura FerreiraSabine Neuss
Apr 4, 2019·Advanced Healthcare Materials·Maaike V J BrahamJacqueline Alblas
Jul 6, 2017·Scientific Reports·Lisa RödlingCornelia Lee-Thedieck
Jan 23, 2017·Journal of Hematology & Oncology·Fang YeGuoji Guo
Jan 7, 2020·Nature Reviews. Materials·Sungwoong KimAnkur Singh
Apr 8, 2020·Journal of Hematology & Oncology·Xia LiHe Huang
Apr 25, 2018·Disease Models & Mechanisms·Jacqui Anne McGovernDietmar Werner Hutmacher
Dec 28, 2019·Biomaterials·Daniel Naveed TavakolThomas Braschler
Mar 9, 2021·Tissue Engineering. Part B, Reviews·Cláudia S OliveiraJoão F Mano
Aug 5, 2020·Advanced Drug Delivery Reviews·Alexander J Najibi, David J Mooney
Sep 9, 2021·Biochemical Society Transactions·Yuen Ting LamSteven G Wise

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Methods Mentioned

BETA
transgenic
genetic modification
flow cytometry
scanning electron microscopy
transmission electron microscopy
PCR

Software Mentioned

GraphPad Prism
GraphPad
FlowJo

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