Endosteal and Perivascular Subniches in a 3D Bone Marrow Model for Multiple Myeloma

TY - JOUR

T1 - Endosteal and Perivascular Subniches in a 3D Bone Marrow Model for Multiple Myeloma

AU - Braham, Maaike V J

AU - Ahlfeld, Tilman

AU - Akkineni, A Rahul

AU - Minnema, Monique C

AU - Dhert, Wouter J A

AU - Öner, F Cumhur

AU - Robin, Catherine

AU - Lode, Anja

AU - Gelinsky, Michael

AU - Alblas, Jacqueline

PY - 2018/5

Y1 - 2018/5

N2 - The bone marrow microenvironment is the preferred location of multiple myeloma, supporting tumor growth and development. It is composed of a collection of interacting subniches, including the endosteal and perivascular niche. Current in vitro models mimic either of these subniches. By developing a model combining both niches, this study aims to further enhance the ability to culture primary myeloma cells in vitro. Also, the dependency of myeloma cells on each niche was studied. A 3D bone marrow model containing two subniches was created using 3D bioprinting technology. We used a bioprintable pasty calcium phosphate cement (CPC) scaffold with seeded osteogenic multipotent mesenchymal stromal cells (O-MSCs) to model the endosteal niche, and Matrigel containing both endothelial progenitor cells (EPCs) and MSCs to model the perivascular niche. Within the model containing one or both of the niches, primary CD138+ myeloma cells were cultured and analyzed for both survival and proliferation. The 3D bone marrow model with combined subniches significantly increasing the proliferation of CD138+ myeloma cells compared to both environments separately. The developed model showed an essential role of the perivascular niche over the endosteal niche in supporting myeloma cells. The developed model can be used to study the expansion of primary myeloma cells and their interactions with varying bone marrow subniches.

AB - The bone marrow microenvironment is the preferred location of multiple myeloma, supporting tumor growth and development. It is composed of a collection of interacting subniches, including the endosteal and perivascular niche. Current in vitro models mimic either of these subniches. By developing a model combining both niches, this study aims to further enhance the ability to culture primary myeloma cells in vitro. Also, the dependency of myeloma cells on each niche was studied. A 3D bone marrow model containing two subniches was created using 3D bioprinting technology. We used a bioprintable pasty calcium phosphate cement (CPC) scaffold with seeded osteogenic multipotent mesenchymal stromal cells (O-MSCs) to model the endosteal niche, and Matrigel containing both endothelial progenitor cells (EPCs) and MSCs to model the perivascular niche. Within the model containing one or both of the niches, primary CD138+ myeloma cells were cultured and analyzed for both survival and proliferation. The 3D bone marrow model with combined subniches significantly increasing the proliferation of CD138+ myeloma cells compared to both environments separately. The developed model showed an essential role of the perivascular niche over the endosteal niche in supporting myeloma cells. The developed model can be used to study the expansion of primary myeloma cells and their interactions with varying bone marrow subniches.

U2 - 10.1089/ten.TEC.2017.0467

DO - 10.1089/ten.TEC.2017.0467

M3 - Article

C2 - 29652626

SN - 1937-3384

VL - 24

SP - 300

EP - 312

JO - Tissue Engineering - Part C: Methods

JF - Tissue Engineering - Part C: Methods

IS - 5

ER -