Artificial Bone Marrow Generates Functional Immune Cells

Artificial marrow could enable the in vitro testing of new drugs to ascertain their effect on bone marrow function. This would facilitate drug development and reveal side effects before human drug trials.

Investigators at the University of Michigan (Ann Arbor, USA) constructed three-dimensional scaffolds with inverted colloidal crystal geometry that mimicked the structural topology of actual bone marrow matrix. The scaffolds were made out of a transparent polymer that allowed the easy passage of nutrients. The scaffolds were molded from a polymer that initially contained tiny spheres ordered like billiard balls. The spheres were then dissolved to leave a well-defined geometry of pores in the scaffold material. The scaffolds were then coated with a layer of transparent nanocomposite to facilitate adhesion of hematopoietic stem cells (HSCs).

Results published in the November 29, 2008, issue of the journal Biomaterials revealed that scaffolds seeded with (HSCs) were capable of supporting expansion of CD34+ HSCs with B-lymphocyte differentiation. The B cells produced antibodies when challenged with a flu virus. Functionality of the artificial bone marrow constructs was confirmed by implantation of scaffolds containing human CD34+ cells onto the backs of severe combined immunodeficiency (SCID) mice with subsequent generation of human immune cells.

"This is the first successful artificial bone marrow," said senior author Dr. Nicholas Kotov, professor of biomedical engineering at the University of Michigan. "Certain stem cells that are essential for immunity and blood production are able to grow, divide, and differentiate efficiently in these scaffolds due to the close similarity of the pores in the scaffold and the pores in actual bone marrow. It has two of the essential functions of bone marrow. It can replicate blood stem cells and produce B cells. The latter are the key immune cells producing antibodies that are important to fighting many diseases."

"The geometrical perfection of the polymer molded by spheres is very essential for reproducibility of drug tests and evaluation of potential drug candidates," said Dr. Kotov. "The scaffold for this work had to be designed from scratch closely mimicking real bone marrow because there are no suitable commercial products."

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