Exp Mol Med.  2017 Nov;49(11):e400. 10.1038/emm.2017.189.

Generation of an osteoblast-based artificial niche that supports in vitro B lymphopoiesis

Affiliations
  • 1Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea. jrrho@cnu.ac.kr
  • 2Agency for Defense Development, Daejeon, Korea.

Abstract

B lymphocytes are produced from hematopoietic stem cells (HSCs) through the highly ordered process of B lymphopoiesis, which is regulated by a complex network of cytokines, chemokines and cell adhesion molecules derived from the hematopoietic niche. Primary osteoblasts function as an osteoblastic niche (OBN) that supports in vitro B lymphopoiesis. However, there are significant limitations to the use of primary osteoblasts, including their relative scarcity and the consistency and efficiency of the limited purification and proliferation of these cells. Thus, development of a stable osteoblast cell line that can function as a biomimetic or artificial OBN is necessary. In this study, we developed a stable osteoblastic cell line, designated OBN4, which functions as an osteoblast-based artificial niche that supports in vitro B lymphopoiesis. We demonstrated that the production of a B220⁺ cell population from Lineage⁻ (Lin⁻) Sca-1⁺ c-Kit⁺ hematopoietic stem and progenitor cells (HSPCs) was increased ~1.7-fold by OBN4 cells relative to production by primary osteoblasts and OP9 cells in coculture experiments. Consistently, OBN4 cells exhibited the highest production of B220⁺ IgM⁺ cell populations (6.7±0.6-13.6±0.6%) in an IL-7- and stromal cell-derived factor 1-dependent manner, with higher production than primary osteoblasts (3.7±0.5-6.4±0.6%) and OP9 cells (1.8±0.6-3.9±0.5%). In addition, the production of B220⁺ IgM⁺ IgD⁺ cell populations was significantly enhanced by OBN4 cells (15.4±1.1-18.9±3.2%) relative to production by primary osteoblasts (9.5±0.6-14.6±1.6%) and OP9 cells (9.1±0.5-10.3±1.8%). We conclude that OBN4 cells support in vitro B lymphopoiesis of Lin⁻ Sca-1⁺ c-Kit⁺ HSPCs more efficiently than primary osteoblasts or OP9 stromal cells.


MeSH Terms

B-Lymphocytes
Biomimetics
Cell Adhesion Molecules
Cell Line
Chemokines
Coculture Techniques
Cytokines
Hematopoietic Stem Cells
In Vitro Techniques*
Lymphopoiesis*
Osteoblasts
Stem Cells
Stromal Cells
Cell Adhesion Molecules
Chemokines
Cytokines
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