In vitro analog of human bone marrow from 3D scaffolds with biomimetic inverted colloidal crystal geometry.
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.
Nichols
Joan E
JE
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA. jnichols@utmb.edu
Cortiella
Joaquin
J
Lee
Jungwoo
J
Niles
Jean A
JA
Cuddihy
Meghan
M
Wang
Shaopeng
S
Bielitzki
Joseph
J
Cantu
Andrea
A
Mlcak
Ron
R
Valdivia
Esther
E
Yancy
Ryan
R
McClure
Matthew L
ML
Kotov
Nicholas A
NA
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D040761:Biomimetic Materials; D001853:Bone Marrow / Q000033:anatomy & histology*; D002454:Cell Differentiation; D002460:Cell Line; D003102:Colloids; D003460:Crystallization; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D013234:Stem Cells / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D003102:Colloids