This work is directly relevant to stem-cell derived therapy that will advance the treatment of a serious injury in humans. This research and product development will provide a novel method for bone graft to address the needs of spinal fusion patients. We will do translational studies to develop bone remodeling therapies.
More than 400,000 Americans require surgery every year for debilitating spinal conditions at an annual cost of more than $3 billion. Spinal fusion surgery is often the only effective procedure for treating pathologic spinal conditions such as scoliosis, degenerative disc disease, spondylolisthesis, or spinal instability, which can cause severe pain by compressing spinal nerves.
The traditional method is to remove the pathology compressing the spinal nerves, and then fuse the spine by removing the disc material and inserting a “cage” between the vertebrae. The current “gold standard” for spine bone replacement is the use of autologous bone harvested from the same patients’ hip. But the patient must undergo two surgeries, one for the hip and one for the spine. Bone chips are harvested from the patient’s hip and inserted into the cage. The bone eventually causes the vertebrae to fuse, which stabilizes the spine. Limitations of harvesting the bone graft from the patient include longer recovery time, increased blood loss, pain and co-morbidities associated with bone harvest from the hip. Patients may be relieved of their spinal conditions, but many end up with chronic hip pain.
With the advancement of minimally invasive surgical techniques the opportunity to identify autograft bone replacements is imperative. The company’s new biomaterial is a synthetic bone graft alternative, which has been shown to stimulate differentiation of stem cells into bone forming osteoblasts. However, the major limitation is that it relies on the patient’s own cells to form new bone. Often, these patients are elderly or have co-morbidities such as diabetes or obesity that has a detrimental effect on their own regenerative potential. Higher yields of bone reformation could be achieved therapeutically by combining human bone marrow-derived stromal cells (hBMSCs) with the synthetic biomaterial. We have shown that stimulation of hBMSCs and differentiation to osteoblasts followed by attachment to the biomaterial enhances the efficacy of this approach. We will clinically evaluate a bone remodeling therapy utilizing a classic tissue-engineering approach that combines sources of cells, signaling factors, and a biomaterial scaffold. The novel cellular bone graft will be elaborated through this work without the need for autologous bone. In the long run this will improve the health of individuals with debilitating spinal conditions.
Statement of Benefit to California:
An estimated 10 million adults suffer from chronic back pain annually, making back pain the number 1 cause of healthcare expenditures in the U.S. with a direct cost of more than $50 billion annually for diagnosis, treatment and rehabilitation. The majority of patients suffer spine problems related to degenerative conditions. These degenerative conditions can result in instability and intrusion into the spinal cord and surrounding nerves, causing back pain and/or radiating pain in the arms or legs. The State of California has approximately 12% of the US population which translates to 1.2 million chronic spine pain individuals with a direct cost of more than $6 billion annually for diagnosis, treatment and rehabilitation. Even for patients that had successful spinal surgery, other problems are associated with bone collection procedures and post-surgical scenarios. Accordingly, an urgent need for a less invasive, more efficient means of doing spinal fusion is needed.
Tissue engineering of bone is important because it has a huge impact on the economy and patient welfare. With an aging population, the needs for improved grafting options that remove the collection of the patient’s own hip bone is necessary to address. Most currently available bone grafts require the patient’s own cells to enter the graft and form bone. Often, these patients are elderly or have co-morbidities such as diabetes or obesity that has a detrimental effect on their own cellular regenerative potential.
Cell implants are a superior alternative for bone repair, particularly for spinal fusion where the endogenous source of progenitor cells is not present in sufficient quantities. This strategy has been brought to clinical trials using stimulated human bone-marrow derived stromal cells (hBMSCs) that have been expanded in cell culture to adopt an osteogenic lineage. By combining novel cell-stimulating technology and FDA-approved hBMSCs and matrix, a robust product will be created. An estimated 5% of the Californian population is expected to be personally impacted with a serious spinal condition at some point in their lives. Of these, 48,000 will be indicated for spinal fusion surgery each year. As such, spinal conditions are one of the most prevalent conditions faced by Californians, and this is only expected to increase as the population continues to age. An estimate of annual revenues for this product is in the $200-$800 million range within the first few years of full commercial launch. Thus, successful completion of this work will not only provide citizens of California much needed advances in bone healing technology of relevance to spinal conditions and improvement in health care but it will also provide high paying jobs and significant tax revenue. This product may also be significantly cheaper to produce than current state of the art technologies, which will result in lower costs to the health care system and increased profitability for the California-based companies.