Oxygen-Deprived Stem Cells More Effective at Making Bone

Depriving stem cells of oxygen and forming them into spheroids before using them to treat bone defects increases their ability to form new bone and repair existing bone, according to a new study led by Kent Leach, Ph.D., a professor of Biomedical Engineering and Orthopaedic Surgery at the University of California, Davis.

The periodical Stem Cells published the study (“Hypoxic Preconditioning of Mesenchymal Stem Cells with Subsequent Spheroid Formation Accelerates Repair of Segmental Bone Defects”) and is the source for the information in this article.

“Cell-based approaches for musculoskeletal tissue repair are limited by poor cell survival and engraftment,” Leach said. “Cells are initially delivered to harsh environments that lack oxygen. We already knew that short-term hypoxic (low oxygen levels) preconditioning of mesenchymal stem cells (MSCs) can prolong cell viability in lab culture, while forming the MSCs [mesenchymal stem cells] into spheroids increases cell survival, trophic factor secretion and tissue formation in vivo.

“So, we hypothesized that preconditioning the MSCs in hypoxia culture before being formed into spheroids might boost the cells’ survival rate and help them to perform better.”

He was right.

To test their theory, the researchers exposed a single-layered culture of human MSCs to 1% oxygen for three days. A control group of cells was limited to ambient air only. Both groups were then formed into spheroids in an engineered hydrogel carrier. The researchers found that the oxygen-deprived cells had a better survival rate than the control group—a factor that increased with the amount of time the cells were exposed to the hypoxic preconditioning.

The next step was to test how the spheroids performed in treating bone defects in rats. They tested spheroids of cells deprived of oxygen against those that were not deprived. They also examined how the spheroids of cells performed compared to oxygen-restricted single cells. “Once again, the oxygen-deprived, spheroid-containing gels induced significantly more bone healing than did gels containing either preconditioned individual MSCs or acellular gels,” Leach said.

He added, “We believe these data demonstrate that preconditioning the cells with a low level of oxygen represents a simple approach for enhancing the therapeutic potential of MSC spheroids when used for bone healing.”