Body builders: using stem cells to cultivate organs - Johns Hopkins University

Science News, March 6, 2004 by Alexandra Goho

Langer's team isn't the only one to have demonstrated the power of the scaffold. Snyder, for instance, seeded polymer scaffolds with neural stem cells and then implanted the complexes in the stroke-damaged brains of mice.

Without any chemical cues, the cells spontaneously differentiated into neurons and other brain cells called oligodendrocytes. The cells extended throughout the polymer fibers making up the scaffold. Meanwhile, neuronal fibers and new blood vessels from the mice infiltrated the regenerating brain tissue.

Christopher Chen at Johns Hopkins University conducted a series of experiments to show how mechanical cues alone can trigger stem cells to differentiate. By modifying a plastic chip's surface the researchers created arrays of different-size islands such that a cell placed on an island could not expand beyond its edge. The cells that had little space remained spherical, while those with more area available flattened out.

In December, at the American Society for Cell Biology's annual meeting in San Francisco, the Johns Hopkins team reported that flattened stem cells turned into bone, and cells that remained round turned into fat. "The cells seemed to detect their own structure;' says Chen.

A gene called Rho appears to be at the heart of this phenomenon. Chen and his colleagues determined that when stem cells are stretched out, the gene turns on and causes the cells to build internal structures that increase tension. This tension then steers the cells toward the bone pathway.

MIX AND MATCH By emulating the body's coordinated use of multiple biological cues, researchers are learning how to get stem cells to do even more of their bidding. Tissue engineers can selectively place different growth factors in different parts of a polymer scaffold, for example, to push a population of stem cells to form multiple layers of different tissue types.

Elisseeff and her coworkers at Johns Hopkins have developed an approach for creating such multilayers. Instead of placing cells on a solid scaffold, the researchers mix the cells into a liquid polymer. When exposed to ultraviolet light, a photosensitive chemical in the liquid causes the material to harden and encapsulate the cells.

To create multiple layers, the researchers mix stem cells and a growth factor into a layer of the liquid polymer and then partially solidify the material with a dose of UV light. A second polymer layer is added with the same stem ceils but a different chemical cue. A final beam of light cinches together the two layers. The researchers are striving for implants that have adjacent layers of cartilage and bone.

Because cartilage is slippery, having a layer of bone underneath it could help surgeons anchor the cartilage to a patient's joint. Currently, surgeons have difficulty- integrating replacement cartilage taken from a donor, with the surrounding tissue, says Elisseeff.

Besides the liquid-polymer approach, tissue engineers are pursuing a host of strategies for guiding stem cell differentiation at different points in a scaffold. One tactic encloses growth factors in degradable microspheres and places them in different locations of the polymer material.