A team of New York Stem Cell Foundation Research Institute scientists report today the generation of patient-specific bone substitutes from skin cells for repair of large bone defects. The study, led by Darja Marolt, PhD, a NYSCF-Helmsley Investigator and Giuseppe Maria de Peppo, PhD, a NYSCF Research Fellow, and published in the Proceedings of the National Academy of Sciences, represents a major advance in personalized reconstructive treatments for patients with bone defects resulting from disease or trauma.
This advance will facilitate the development of customizable, three-dimensional bone grafts on-demand, matched to fit the exact needs and immune profile of a patient. Taking skin cells, the NYSCF scientists utilized an advanced technique called “reprogramming” to revert adult cells into an embryonic-like state. These induced pluripotent stem (iPS) cells carry the same genetic information as the patient and they can become any of the body’s cell types.
The NYSCF team guided these iPS cells to become bone-forming progenitors and seeded the cells onto a scaffold for three-dimensional bone formation. They then placed the constructs into a device called a bioreactor, which provides nutrients, removes waste, and stimulates maturation, mimicking a natural developmental environment.
“Bone is more than a hard mineral composite, it is an active organ that constantly remodels. Blood vessels shuttle important nutrients to healthy cells and remove waste; nerves provide connection to the brain; and, bone marrow cells form new blood and immune cells,” said Marolt.
Previous studies have demonstrated the bone-forming potential from other cell sources, yet serious caveats for clinical translation remain. A patient’s own bone marrow stem cells can form bone and cartilaginous tissue, not the underlying vasculature and nerve compartments; and, embryonic stem cell derived bone may prompt an immune rejection. The NYSCF scientists chose to work with iPS cells to overcome these limitations, comparing iPS sources with embryonic stem cells and bone marrow derived cells.
“No other research group has published work on creating fully-viable, functional, three-dimensional bone substitutes from human iPS cells. These results bring us closer to achieving our ultimate goal, to develop the most promising treatments for patients,” said de Peppo.