Patient-specific bone substitutes have been produced by a team of scientists from the New York Stem Cell Foundation. Darja Marolt and Giuseppe Maria de Peppo from the New York Stem Cell Foundation (NYSCF) led the study that demonstrated that customizable, three-dimensional bone grafts that can be produced on-demand for patients from their own cells.
Marolt and de Peppo and their co-workers used skin grafts from their patients to isolate skin fibroblasts that were reprogrammed to induced pluripotent stem cells (iPSCs). Because iPSCs are made from the patient’s own cells, they have the same profile of cell surface proteins as the patient’s own tissues. Therefore, they are very unlikely to be rejected by the patient’s immune system. Also, iPSCs have the ability to differentiate into any cell type found in the adult body, and therefore, can be used to form bone cells.
After deriving iPSCs from patient skin cells, de Peppo, Marolt, and colleagues coaxed the cells to form osteoblasts (the cells that form bone), and seeded them onto a scaffold that mimicked three-dimensional bone structure. These structures were grown in a bioreactor that fed the cells oxygen and nutrients.
According to Marolt, “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.”
Previous studies have demonstrated that cells from other sources also possess bone-forming potential. However, these same studies have revealed serious shortcomings of the clinical potential of such cells. A patient’s own bone marrow stem cells can form bone and cartilaginous tissue, but not the accompanying underlying vasculature and nerve compartments. Also, embryonic stem cell derived bone may prompt an immune rejection. Therefore, the use of iPSCs can overcome many of these limitations.
As de Peppo noted: “No other research group has published work on creating fully viable functional three-dimensional bone substitutes from humans iPS cells. These results bring us closer to achieving our ultimate goal, to develop the most promising treatments.”
Since bone injuries and defects are often treated with bone grafts that are taken from other parts of the body or a tissue bank. Alternatively, synthetic alternatives can also be used, but none of these possibilities provide the means for complex reconstruction and they may also be rejected by the immune system, or fail to integrate with surrounding connective tissue. n the case of trauma patients who suffer from shrapnel wounds or vehicular injuries , the traditional treatments provide only limited functional and cosmetic improvements.
To access the integrity of the bioreactor-made bone, the NYSCF team implanted them into animals. Implantation of undifferentiated iPSCs formed tumors, but transplantation of the iPSC-derived bone produced no tumors, but also produced grafts that effectively integrated into the bones, connective tissues and blood vessels of the animals.
Susan Solomon, CEO of NYSCF, said of this work, “Following from these findings, we will be able to create tailored bone grafts, on demand, for patients without any immune rejection issues. She continued: “it is the best approach to repair devastating damage or defects.”
The therapeutic relevance of this work aside, these adaptive bone substitutes can also serve as models for bone development and various bone pathologies. Such bone exemplars could serve as models for drug testing and drug development.