Nichols Joan E, Cortiella Joaquin, Lee Jungwoo, Niles Jean A, Cuddihy Meghan, Wang Shaopeng, Bielitzki Joseph, Cantu Andrea, Mlcak Ron, Valdivia Esther, Yancy Ryan, McClure Matthew L, Kotov Nicholas A
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA.
Biomaterials. 2009 Feb;30(6):1071-9. doi: 10.1016/j.biomaterials.2008.10.041. Epub 2008 Nov 29.
In vitro replicas of bone marrow can potentially provide a continuous source of blood cells for transplantation and serve as a laboratory model to examine human immune system dysfunctions and drug toxicology. Here we report the development of an in vitro artificial bone marrow based on a 3D scaffold with inverted colloidal crystal (ICC) geometry mimicking the structural topology of actual bone marrow matrix. To facilitate adhesion of cells, scaffolds were coated with a layer of transparent nanocomposite. After seeding with hematopoietic stem cells (HSCs), ICC scaffolds were capable of supporting expansion of CD34+ HSCs with B-lymphocyte differentiation. Three-dimensional organization was shown to be critical for production of B cells and antigen-specific antibodies. Functionality of bone marrow constructs was confirmed by implantation of matrices containing human CD34+ cells onto the backs of severe combined immunodeficiency (SCID) mice with subsequent generation of human immune cells.
骨髓的体外复制品有可能为移植提供持续的血细胞来源，并作为一个实验室模型来研究人类免疫系统功能障碍和药物毒理学。在此，我们报告了一种基于具有倒置胶体晶体（ICC）几何结构的三维支架开发的体外人工骨髓，该支架模仿了实际骨髓基质的结构拓扑。为促进细胞黏附，支架涂覆有一层透明纳米复合材料。在用造血干细胞（HSCs）接种后，ICC支架能够支持CD34+ HSCs的扩增并伴有B淋巴细胞分化。三维结构对于B细胞和抗原特异性抗体的产生至关重要。通过将含有人类CD34+细胞的基质植入重症联合免疫缺陷（SCID）小鼠背部，随后产生人类免疫细胞，证实了骨髓构建体的功能。
