Tissue engineered models of healthy and malignant human bone marrow

Abstract

Tissue engineering is becoming increasingly successful in providing in vitro models of human tissues that can be used for ex vivo recapitulation of functional tissues as well as predictive testing of drug efficacy and safety. From simple tissue models to microphysiological platforms comprising multiple tissue types connected by vascular perfusion, these "tissues on a chip" are emerging as a fast track application for tissue engineering, with great potential for modeling diseases and supporting the development of new drugs and therapeutic targets. We focus here on tissue engineering of the hematopoietic stem and progenitor cell compartment and the malignancies that develop in the human bone and bone marrow. Our overall goal is to demonstrate the utility and interconnectedness of improvements in bioengineering methods developed in one area of bone marrow studies for the remaining, seemingly disparate, bone marrow fields.

The extracellular matrix of hematopoietic stem cell niches

“…Bringing crucial parameters of the natural HSC niche — found in in vitro and in vivo studies — in this way together into one system is the basis for creating so-called artificial HSC niches. The number of studies trying to recreate the HSC niche by mimicking these factors and parameters to a certain extent is constantly rising and for a complete overview the reader is referred to other excellent recent reviews focusing on this topic [510] , [532] . Many different approaches including different cell types, scaffolds, 3D culture techniques and bioreactors were taken, and, so far, none of these approaches became dominant in the field [532] .…”

“…The number of studies trying to recreate the HSC niche by mimicking these factors and parameters to a certain extent is constantly rising and for a complete overview the reader is referred to other excellent recent reviews focusing on this topic [510] , [532] . Many different approaches including different cell types, scaffolds, 3D culture techniques and bioreactors were taken, and, so far, none of these approaches became dominant in the field [532] . Currently, these artificial HSC niches are mainly used for HSC multiplication for potential future application of such expanded cells in cellular therapies.…”

Tissue Engineering for Mimics and Modulations of Immune Functions

“…HSCs develop into common myeloid precursors and common lymphoid precursors in bone marrow. [ 14 ] Common myeloid precursors further develop into antigen‐presenting cells including DCs and macrophages. Common lymphoid precursors develop into T precursors, which migrate to and mature in the thymus, and B lymphocytes, the majority of which migrate to SLOs, while the rest are deleted or edited.…”

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

“…Nonetheless, the development of a functionally effective model capable of showing BMN diversity and dynamism with the translational potential for disease modeling is still challenging. No single approach has been adopted as the standard in the field [ 63 , 64 , 65 ], however, different models have succeeded in reproducing some particular and restricted aspects of specific BM contexts. For example, the first attempts at reproducing cell-cell interactions started with the co-culture of HSCs and different BMN-forming cells, such as ECs, OBs or MSCs [ 66 , 67 , 68 ].…”