(P 217) In-Vitro Analog of Human Bone Marrow From 3D Scaffolds with Inverted Colloidal Crystal Topology

• Published in: Tissue engineering. Part A Vol. 14; no. 5; p. 867
• Main Authors: Nichols, JE, Kotov, NA, Niles, JA, Warner, S, Cantu, A, Mlcak, R, Yancy, R, Valdivia, E, Cortiella, J
• Format: Journal Article
• Language: English
• Published: 01.05.2008
• ISSN: 1937-3341; 1937-335X

In-vitro replicas of bone marrow could provide a continuous source of blood cells for transplantation or serve as a laboratory model to examine 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 hemato-poietic stem cells (HSC), ICC scaffolds were capable of supporting expansion of CD34+ HSCs with B-lymphocyte differentiation. 3D organization was shown to be critical for production of B cells and antibody. Functionality of bone marrow constructs was confirmed by implantation of matrices containing human CD34+ cells onto the backs of SCID mice with generation of human immune cells. Animals were sacrificed after 2 weeks and then the implanted matrix, mouse bone marrow and spleens were collected for leukocyte subset phentotyping. Examination of the cells populating the spleens of these mice indicated that the majority of cells (89%) were also of human origin as indicated by evaluation of MHC class I co-staining and the predominant cell type found was CD 19+ IgD+IgM positive. Median engraftment time for bone marrow reconstitution by transplant of bone marrow or cord blood is typically 18-26 days. One can suggest that engraftment of HSCs in the artificial bone marrow construct with continued production of CD34+ cells is similar to that seen in human or murine reconstitution of irradiated marrow.