Differentiation of Pluripotent Stem Cells for Skeletal Regeneration

Bone injuries and bone diseases sometimes require bone grafts for proper treatment. In order to find bone for implantation, orthopedic surgeons often take bone from other locations in the body, use bone from cadavers or synthetic compounds that promote the formation of new bone. Bone grafting is a complex surgical procedure and even though it can replace missing bone, it poses a significant health risk to the patient, and sometimes completely fails to foster proper healing.

Bone has the ability to regenerate, but it requires very small fracture space or some sort of scaffold in order to make new bone. Bone grafts can provide that scaffold. A bone graft can be “autologous,” which simply means that the bone is harvested from the patient’s own body (often from the iliac crest), or the graft can be an allograft, which consists of cadaveric bone usually obtained from a bone bank. Finally, synthetic bone grafts are made from hydroxyapatite or some other naturally occurring, biocompatible substance such as Bioglass, tricalcium phosphate, or calcium sulfate.

Making natural bone from stem cells is one of the goals of regenerative medicine, and work from Irving I. Weissman at Stanford University has shown that this hope is certainly feasible.

Weissman and his colleagues evaluated the ability of embryonic stem cells and induced pluripotent stem cells to form bone in a culture environment known to induce bone formation in most circumstances. This culture system (known as an osteogenic microniche) consisted of a scaffold made of poly – L-lactate coated with hydroxyapatite and stuffed with a growth factor called bone morphogen protein-2 (BMP-2). BMP-2 is a known inducer of bone formation and this scaffold is placed inside the bone of a laboratory animal that has suffered a fracture.

After implanting pluripotent stem cells into these osteogenic microniches, they were very pleasantly surprised to find that both embryonic stem cells and induced pluripotent stem cells embedded themselves into the scaffold and differentiated into bone making cells (osteoblasts). They also made new bone and did so without forming any tumors.

These results suggest that local signals from the implanted scaffold and the genera environment within the bone directed the cells to survive and differentiate into osteoblasts. Thus pluripotent stem cells may have the clinical capacity to regenerate bone, which would, potentially preclude the need for risky bone grafting procedures.

See Levi, B. et al., In vivo directed differentiation of pluripotent stem cells for skeletal regeneration. PNAS November 20, 2012, doi:10.1073/pnas.1218052109.