Bioengineering the Bone Marrow Vascular Niche

Abstract

The bone marrow (BM) tissue is the main physiological site for adult hematopoiesis. In recent years, the cellular and matrix components composing the BM have been defined with unprecedent resolution, both at the molecular and structural levels. With the expansion of this knowledge, the possibility of reproducing a BM-like structure, to ectopically support and study hematopoiesis, becomes a reality. A number of experimental systems have been implemented and have displayed the feasibility of bioengineering BM tissues, supported by cells of mesenchymal origin. Despite being known as an abundant component of the BM, the vasculature has been largely disregarded for its role in regulating tissue formation, organization and determination. Recent reports have highlighted the crucial role for vascular endothelial cells in shaping tissue development and supporting steady state, emergency and malignant hematopoiesis, both pre- and postnatally. Herein, we review the field of BM-tissue bioengineering with a particular focus on vascular system implementation and integration, starting from describing a variety of applicable in vitro models, ending up with in vivo preclinical models. Additionally, we highlight the challenges of the field and discuss the clinical perspectives in terms of adoptive transfer of vascularized BM-niche grafts in patients to support recovering hematopoiesis.

Isolation, Maintenance and Expansion of Adult Hematopoietic Stem/Progenitor Cells and Leukemic Stem Cells

“…Bioreactor is an engineered system that allows culturing large amounts of CD34 + CB-HSCs through automated control over medium supply, waste removal and agitation [ 327 ]. Microfluidic devices mimic the vascular niche by continuously supplying nutrients and oxygen, while generating gradients (e.g., oxygen, calcium ions, cytokines and small molecules) [ 328 , 329 ]. Bone marrow-on-a-chip is an even more complex microfluidic system, where the colonization of the 3D matrix by niche cells takes place in the BM in vivo [ 330 , 331 ].…”

Editorial: The Dynamic Interface Between Vascular Blood Vessels to Blood Forming Hematopoietic Stem Cells in Health and Disease

“…Despite being largely disregarded in the first models, vascular endothelial cells have gradually been included in these constructs. Bessy and colleagues have reviewed the field of bone-tissue bioengineering with a particular focus on vascular implementation and integration (Bessy et al, 2021). The field still faces the big challenge of transitioning from experimental models to translational research.…”

The Mesenchymal Niche in Myelodysplastic Syndromes

“…Bone marrow endothelial cells (BMECs) play a crucial role in the maintenance of HSCs: they form a network of blood vessels that provide angiocrine signals regulating HSC development and homeostasis [ 15 , 16 ]. Under pathological conditions, BMECs also play an important role in the development and progression of diseases [ 17 ]. Indeed, BMECs have been shown to be a fundamental source of angiocrine factors that promote the development and survival of T-cell acute lymphoblastic leukemia (ALL) in the BM niche [ 18 ].…”