Artificial bone marrow that continuously can make red and white blood cells has been created in a U-M lab. This development could lead to simpler pharmaceutical drug testing, closer study of immune system defects and a continuous supply of blood for transfusions.
The substance grows on a 3-D scaffold that mimics the tissues supporting bone marrow in the body, says Nicholas Kotov, a professor in the Department of Chemical Engineering, Department of Materials Science and Engineering, and Department of Biomedical Engineering.
The marrow is not made to be implanted in the body, as are most 3-D biomedical scaffolds. It is designed to function in a test-tube.
Kotov, principal investigator, is an author of a paper about the research currently published online in the journal Biomaterials. Joan Nichols, professor from the University of Texas Medical Branch, collaborated on many aspects of this project.
“This is the first successful artificial bone marrow,” Kotov says. “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.”
Blood stem cells give rise to blood as well as several other types of cells. B cells, a type of white blood cell, battle colds, bacterial infections and other foreign or abnormal cells including cancers.
Cancer-fighting chemotherapy drugs strongly can suppress bone marrow function, leaving the body more susceptible to infection. The new artificial marrow could allow researchers to test how a new drug at certain potencies would affect bone marrow function, Kotov says. This could assist in drug development and catch severe side effects before human drug trials.
Bone marrow is a complicated organ to replicate, Kotov says. Vital to the success of this new development is the three-dimensional scaffold on which the artificial marrow grows. This lattice had to have a high number of precisely sized pores to stimulate cellular interaction.
The scaffolds are made out of a transparent polymer that nutrients easily can pass through. To create the scaffolds, scientists made a mold of the polymer with tiny spheres ordered like billiard balls. Then they dissolved the spheres to leave the perfect geometry of pores in the scaffold.
The scaffolds then were seeded with bone marrow stromal cells and osteoblasts, another type of bone marrow cell.
The researchers demonstrated that the artificial marrow gives a human-like response to an infectious New Caledonia/99/H1N1 flu virus. This is believed to be a first.
To determine whether the substance behaves like real bone marrow, the scientists implanted it in mice with immune deficiencies. The mice produced human immune cells and blood vessels grew through the substance.
The paper is called “In vitro analog of human bone marrow from 3D scaffolds with Biomimetic inverted colloidal crystal geometry.”
