Using Nell-1 to harness the osteogenic potential of adult stem cells

Funding Type: 
Disease Team Research I
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Traumatic injuries are responsible for over 15% of the global health burden. Many are musculoskeletal injuries that, if untreated, can cause long-term disability. Bone regeneration is a natural process that is critical for fracture repair and for the healing of bone grafts used during skeletal reconstruction. However, aging and metabolic bone diseases like osteoporosis can negatively affect the bone regeneration capacity by reducing stem cell numbers and cell activity. The failure to heal fractures in osteoporotic patients, for instance, has been reported to be as high as 50%. Osteoporosis is by far the most common systemic disease of skeletal fragility. Up to 50% women and 20% men over age 50 will suffer an osteoporosis-related fracture in their remaining lifetime. Furthermore, osteoporosis is frequently associated with other diseases like i] spinal cord injury, in which fractures are the result of limb disuse, ii] Parkinson’s disease and multiple sclerosis, in which there is an increased risk of life threatening fractures from falls, iii] malignant neoplasms invading bone that increase pathologic fracture risk and iv] organ transplant patients on chronic steroid-mediated immunosuppression. Due to changing demographics and increased life expectancy, annual osteoporotic fracture costs are projected to increase from $20 to $240 billion worldwide by 2040.

Bone regeneration therapies can be cell- or non-cell based. Cell-based therapies either take the patient’s own cells (which causes significant pain and discomfort) or use cells from deceased donors. The latter requires extensive processing to remove immune components, and do not work as well as the patient’s own bone and stem cells. Non-cell based therapies are either less effective (deceased donor bone with no cells) or have undesirable effects (e.g., bone morphogenetic proteins can cause life threatening neck swelling). Current therapies also do not address the needs of osteoporotic populations where the healing environment is suboptimal and/or bone harvest from the patient’s own hip can further damage already weak bone.

To address the unmet medical need, our team has developed an adult stem cell product that exceeds the efficacy and safety of current bone repair therapies. Stem cells hold great promise in their ability to regenerate damaged tissues. However, until now, stem cells have been difficult to identify and isolate in numbers sufficient for medical use without cumbersome cell culture. We have developed a highly effective and reproducible method to isolate and purify high numbers of a person’s own stem cells from fat tissues obtained through liposuction, a relatively safe and common cosmetic surgery procedure. In addition, we have developed a highly potent and bone-specific growth factor to help these stem cells form bone. Combined, the stem cell-growth factor product forms an environment that can significantly regenerate bone in normal as well as osteoporotic patients.

Statement of Benefit to California: 

This well developed proposal aims to enable IND submission for the use a novel growth factor to direct the differentiation of human perivascular stem cells within a osteogenic carrier for bone regeneration. This highly multi-disciplinary project has many near-term and long-term benefits to the State of California.

1. California’s climate is attractive to people all ages, particularly the elderly. Unfortunately, a large fraction of the aged population suffers from osteoporosis. In 1998, the health care burden for osteoporosis exceeded $2.4 billion in California alone. A whopping 64% of the $2.4 billion was caused by hip fracture. By promoting the repair of both normal and healing-impaired bone in a safe and effective manner, our mature technology will reduce the long term health care burden for California’s public health insurance program.

2. Besides direct health cost, bone injuries and diseases can result in hospitalizations and long term disabilities that can lead to sick days and lost productivity. The hard working Californians are responsible for California’s annual gross domestic product of $1.8 trillion, which rank our state among the top eight largest economies in the world. By promoting the repair of both normal and healing-impaired bone in a safe and effective manner, our mature technology will reduce the loss of work productivity at the front end, reduce work disability costs, and reduce the loss of state income tax.

3. California boasts a highly diverse population with numerous ethnic groups. While this diversity offers amazing opportunities for cross cultural discoveries, some ethnic groups (e.g. Latino and some Asian descents) may be disadvantaged in terms of donor matches for traditional stem cell sources. Our stem cell therapy can benefit these minorities and reduce the long term health care burden for California’s public health insurance program.

4. This project directly adds jobs at {REDACTED} and at the California-based companies that are involved in this project.

5. This project will procure supplies and equipment from strategic California-based companies.

6. This project will produce intellectual property that is owned by the {REDACTED}.

7. This mature project is precisely the type of cutting-edge, ethical, multi-disciplinary stem cell project that Californians imagined when they approved proposition 71 in 2004. The establishment of CIRM has transformed the research infrastructure at {REDACTED}, increased our ability to recruit world class stem cell scientists, and attracted the attention of superb scientists from other disciplines to this new field. Working together, our team has compiled an impressive list of accomplishments and we are confident in our abilities to take this project to IND submission in a timely fashion. Funding of this project will fulfill the promise of proposition 71.