Three dimensionalde novomicro bone marrow and its versatile application in drug screening and regenerative medicine

Abstract

The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field.

A parallelized, perfused 3D triculture model of leukemia for in vitro drug testing of chemotherapeutics

“…Here, the effectivity of the chemotherapeutics CPA and 5-FU on the survival of KG-1a cells was greater in standard 2D cultures than in the biomimetic perfused 3D system, indicating that such effects could be overestimated in 2D cultures. This is in line with previous studies showing that the resistance of LCs is increased in biomimetic 3D systems [19,[56][57][58][59]. Similar to HSPCs, LCs may reside in a quiescent state resulting in resistance against chemotherapeutics [12,60].…”

In Situ Articular Cartilage Regeneration through Endogenous Reparative Cell Homing Using a Functional Bone Marrow-Specific Scaffolding System

“…The activated stem cells then migrate into the injury site and play an important role during tissue repair process . Despite tissue-specific stem cells that are critical for tissue homeostasis and repair, the bone marrow, which harbors multiple distinct types of multipotent cells, has been proven to be a potential cell source reservoir that contributes to the regenerative capacity of other tissues. − Therefore, it is worthwhile to target bone marrow-derived multipotent cells to be effectively homing into the site of injury. As such, microfracture that works by drilling into subchondral bone to mobilize bone marrow has been applied to facilitate cartilage repair.…”

The extracellular matrix of hematopoietic stem cell niches

“…The next level of complexity can be added by introducing supporting cells such as osteoblasts or MSCs into the systems and/or by working with primary leukemic cells. Such studies showed the supportive character of the microenvironment for leukemic cells which leads to enhanced resistance to the investigated chemotherapeutics [551] , [552] . 3D co-culture systems were also applied to investigate the importance of the CXCL12/CXCR4 axis as a target during leukemia treatment.…”