Year 1

Background: unsuccessful bone repair
Most organs can regenerate cells lost to ageing, exposure to adverse conditions, ephemeral lifespan, disease or injury. Regenerative systems are complex combinations of growth factors and anchorage molecules which support, guide and control the maturation of specialized stem cells. The regenerative process may still fail, for multiple reasons. Bone fractures will sometimes not heal spontaneously because parts of the broken bone do not join anymore, or because bone regeneration itself is impaired, like in osteoporosis, a frequent condition that affects post-menopause females and elderly people of both genders.

A novel class of bone-healing stem cells
Since specialized bone-forming cells have not been identified, which stem cells could be used for the cell therapy of bone fractures? We have identified and purified novel stem cells, localized around blood vessels and therefore named perivascular stem cells (PSCs). We have also demonstrated that Nell-1, a potent osteogenic growth factor we have developed, efficiently turns PSCs into bone cells. In 2011, we have been granted support by the California Institute for Regenerative Medicine to develop a product to heal critically fractured bones in osteoporotic – or not – patients or to perform spine fusion in order to correct skeletal defects. PSCs will be purified from the patient’s own fat tissue, a well-documented, rich source of these cells, and embedded in a biocompatible scaffold in the presence of the bone forming growth factor. The resulting compound, inserted at the site of the fracture, will provide bone-forming stem cells 1-precisely characterized in terms of origin and identity; 2- derived from the patient, hence not rejected; 3- not cultured, therefore similar to their natural counterparts.

Progress after one year of research supported by CIRM
We are now close to the end of the first year of our CIRM supported studies. In this initial period we have, first, validated the stem cells of use with regard to stringent biologic criteria: how many of these cells can be purified from fat tissue? How viable and pure are these cells after the sorting process? Do stem cell numbers and quality depend on the age, sex and corpulence of the donor? Following analysis of about 80 distinct fat harvests (lipoaspirates) we have determined that robust bone forming PSC can be reliably purified, in sufficient numbers, from male and female donors in all age and weight ranges. We have also shown that PSC are at least as good, in terms of bone forming potential, than conventional mesenchymal stem cells (the candidate stem cells, so far, to be used for cell therapies of bone defects amd injuries), while being significantly superior regarding purity and safety.
Transplantation experiments in mice and rats have revealed that the combination of PSC and the Nell-1 growth factor ensures the most efficient bone regeneration, but that PSC do not give rise to tumors, an important verification in any protocol involving transplantation. These experiments have also demonstrated that PSC stimulate the formation of new blood vessels, an essential requisite for efficient wound healing and tissue repair.
Finally, we have embarked on the development of a larger animal model of bone regeneration, that will be used in the second and third years of the projects.
In summary, we have reached all the milestones and met the deadlines planned in the original project. The next year will see the further validation of the protocol and the beginning of the development of a stem cell/scaffold/growth factor combination product in the perspective of trials in human patients.