Dual stem cell transplantation in tissue engineered scaffolds for the repair of spinal cord injury
Spinal cord injury (SCI) is a problem that affects approximately 2 million people worldwide. Chronic health problems for patients suffering partial and complete spinal cord injury impose tremendous emotional and financial burdens on patients, families, health care providers, and the health delivery system. There remains no adequate treatment for SCI, but stem cell and regenerative medicine technologies hold substantial promise. Although a handful of early trials involving the implantation of bone marrow derived mesenchymal stem cells (MSCs) are underway, these studies involve the use of cells that appear to support spinal neuron survival and recovery, but do not replace neurons themselves that were lost due to injury.
Much research has focused on generating supportive cells such as oligodendrocytes and glial-like cells which have each been shown to promote the survival and recovery of spinal cord neurons that were not lost due to injury. Unfortunately, the injured spinal cord is an environment that is inhibitory to neurons themselves, and inflammation at the injury site can be hostile to transplanted cells. Recently, however, methods have been developed that hold promise for a strategy in which one type of implanted stem cell may chaperone a second type of stem cell, simultaneously protecting the susceptible cell from the challenging SCI environment while drawing on the strengths of both cells to regenerate the injured spinal cord. Furthermore, if these cells are implanted to the injury site in a tissue-engineered "architectural" matrix that can provide the cells with instructions guiding their behavior towards regeneration, a powerful treatment modality will emerge. This proposal seeks to fabricate such a dual stem cell-seeded implantable matrix, and demonstrate that it is capable of safely improving functional outcome after spinal cord injury.
It is estimated that ten to fifteen thousand new spinal cord injuries (SCI) occur each year, adding to the 2 million chronic sufferers. The physical, emotional, financial, and social burdens of Californians with SCI are tremendous. Because the consequences of SCI, including conditions such as paralysis, are usually lifelong and impact nearly every aspect of a patient's life, the burdens specific to this injury are disproportionately large compared to many chronic health problems. It is the aim of the proposed research to develop a dual stem cell tissue-engineered implant that will improve the recovery of motor function following injury. If successful, the treatment will benefit not only patients, but their families and care givers. By enabling individuals to regain their abilities for activities of daily living (ADLs), a successful treatment would shorten the chronic nature of SCI, reduce the secondary health consequences, and would therefore offer economic benefit to California patients, families, and health care systems. A successful treatment would further benefit the California biotechnology industry by creating jobs that would help bring the technology to clinical reality. Finally, such a treatment modality would create unique learning and career development opportunities for California students and trainees in areas ranging from biomedical research, to physical therapy, bioengineering, and clinical specialties.