Ann Arbor-based U-M Researchers Create Cell Therapy Designed to Heal Bone Fractures

Researchers at Ann Arbor’s University of Michigan are reprogramming adult stem cells from bone marrow so they can be injected directly into a wound and grow into bone.
Bone regeneration supplies
U-M researchers are growing and programming adult stem cells to grow into bone after a break. // Photo by Robert Coelius, courtesy of the University of Michigan

Researchers at Ann Arbor’s University of Michigan are reprogramming adult stem cells from bone marrow so they can be injected directly into a wound and grow into bone.

Jan Stegemann, a U-M professor of biomedical engineering, is using marrow-derived progenitor cells, which maintain the ability to differentiate into several different cell types. Testing in mice has shown that the therapy can accelerate the bone regeneration process after injury.

The therapy is designed to target large, complex defects, where a lot of bone has been lost and the tissue around it has been damaged. The wounds don’t always heal. A current treatment for this is to take bone from another part of the patient’s body, crush it, and put it in the wound to help it regenerate. However, this requires a second surgery and creates two spots for the body to heal.

In Stegemann’s therapy, progenitor cells are taken from the patient, grown outside the body, and stimulated to be very effective at creating bone tissue. They are delivered directly to where they need to be, and the process makes the cells more likely to survive and regenerate bone.

“(Progenitor cells) can be derived from the bone marrow or other tissues. You can even get them from liposuctioned fat,” says Stegemann. “You can isolate those cells and then expand their number until you have many multiples of the initial number of cells that you took from the body. You can also treat them so that they form the type of tissue you are interested in.

“In our case, we treat them with specific biological factors in order to help them differentiate into bone cells. We also use carefully selected biomaterials, materials that cells recognize and can bind to. Through this binding, these materials also give the progenitor cells specific cues to form bone. Therefore, by combining the biological stimulation with the appropriate physical environment, we are able to get the cells to really potently regenerate new tissue.”

Because large bone wounds don’t have much blood supply and there is lots of inflammation, there isn’t much healing, and injected cells will likely die or migrate away from the site. To combat this, Stegemann’s team created microtissues, which are small protein beads that have up to hundreds of cells inside each one. The beads have the physical and biochemical cues that allow the cells to survive and function after they are transplanted.

The cells in the microtissues are injected into the bone through a needle as a paste. In some instances, there’s no need for surgery.

The team thinks it has developed a platform technology through this process that could be used for other types of tissue regeneration. For example, Type I diabetes is caused when a cell type dies, so replacing the cell type with a new population could be an effective treatment.

An article about the work, titled “Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects,” has been published in the journal Biomaterials.

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