Enhancing Stem Cells With Oxygen and Forming Them Into Spheroids Leads to Better Bone Repair

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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 in STEM CELLS.

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 in STEM CELLS.

The study was led by Kent Leach, Ph.D., a professor of Biomedical Engineering and Orthopaedic Surgery at the University of California, Davis. “Cell-based approaches for musculoskeletal tissue repair are limited by poor cell survival and engraftment,” he 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 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.”

To test their theory, the researchers exposed a single-layered culture of human MSCs to 1 percent oxygen for three days, while a control group of cells was limited to ambient air only. Both groups were then formed into spheroids trapped in an engineered hydrogel carrier. As anticipated, 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 animals – in this instance, rats. This time, not only did they test spheroids of cells deprived of oxygen against those that were not deprived, they also looked at how the spheroids of cells performed compared to oxygen-restricted single cells (that is, cells working alone rather than in a spheroid group.)

“Once again, the oxygen-deprived, spheroid-containing gels induced significantly more bone healing than did gels containing either preconditioned individual MSCs or acellular gels,” Dr. Leach said.

“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,” he concluded.

“Mesenchymal Stem/Stromal Cells have great potential, and are in numerous clinical trials for different disorders and injuries.” said Jan A. Nolta, PhD, Editor-in-Chief of STEM CELLS and director of the Stem Cell Program and Institute for Regenerative Cures at UC Davis School of Medicine, “A key factor for improving bone repair is to maintain the cells in place long enough to promote matrix deposition and healing. Dr. Leach and team are leaders in MSC spheroid technology and have further improved it to extend in vivo survival and bone repair, in the current study. This is an important advance for the field.”

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The full article, “Hypoxic Preconditioning of Mesenchymal Stem Cells with Subsequent Spheroid Formation Accelerates Repair of Segmental Bone Defects,” can be accessed at http://www.stemcells.com.

About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® (http://www.StemCells.com) is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST® (http://www.TheOncologist.com) is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® (http://www.StemCellsTM.com) is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www.wiley.com.

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