Hans S. Keirstead
Professor of Anatomy and Neurobiology, and Neurological Surgery, Anatomy & Neurobiology
|Regeneration, degeneration, spinal cord, injury, myelin, demyelination, axon, growth cone, and plasticity|
|URLs||Reeve-Irvine Research Center|
|Sue and Bill Gross Stem Cell Research Center|
|Anatomy and Neurobiology|
|Appointments||Postdoctoral Study in Neurobiology, University of Cambridge, England 1995-1999|
1. Preventing the phase of secondary degeneration that follows an initial trauma
2. Removing growth-inhibitory myelin from the vicinity of an injury site, facilitating axonal regeneration
3. Transplanting human stem cell derivatives into regions of spinal cord injury
The focus of the Keirstead laboratory is the development of strategies to limit degeneration and enhance regeneration after spinal cord injury, of both axons and myelin. Currently, the laboratory has three primary research areas, 1) preventing the phase of secondary degeneration that follows an initial trauma; secondary degeneration normally occurs after a traumatic injury, increasing the size of the lesion and the resulting functional deficit, 2) removing growth-inhibitory myelin from the vicinity of an injury site, which allows axons to regenerate, and 3) transplanting growth-permissive cell populations into regions of spinal cord injury in order to repair lost myelin and provide an environment that favors axon regeneration. These therapies are often combined in an effort to further enhance repair.
For treatment of acute SCI, the Keirstead laboratory is investigating strategies to reduce or eliminate the posttraumatic enlargement of spinal cord injury sites that normally occurs after traumatic injury. This process is largely mediated by the immune system, and the laboratory has developed methods of inhibiting the deleterious components of the immune response to CNS injury. These methods of reducing the immune response to injury result in a near elimination of secondary degeneration, which means that far less tissue is lost after an injury and functional impairment is greatly decreased. The human reagents necessary for clinical trials have recently been generated, and the program is being developed for human therapy.
The removal of myelin from the spinal cord is another method developed to treat spinal cord injury. Myelin inhibits regrowth of injured fibers, so the removal of myelin around an injury site renders the spinal cord permissive for repair. Our lab has demonstrated that this treatment is effective in facilitating repair of spinal cord injuries in chickens, rats and mice.
Stem Cell Research
Dr. Keirstead was the first researcher in North America to gain access to the federally approved hESC lines for CNS trauma research. He is Co-Director of the UCI Stem Cell Research Initiative, has testified to the CA Senate on several occasions regarding the potential of stem cells, was an advisor to the Davis CA government on stem cell policy, represented the spinal cord research community at an NIH-sponsored policy meeting in Sweden to advise the NIH on stem cell funding issues, is a Scientific Advisory Board Member of the California Stem Cell Initiative, and maintains working relationships with several stem cell companies and venture capital groups in the United States and Sweden. His stem cell research forms the basis of a clinical trial that is being developed (i.e. it is in the pre-clinical phase). His current stem cell research utilizes 2 hESC lines. He developed a method to differentiate hESC lines into high purity oligodendrocyte progenitor populations, demonstrating for the first time that hESC lines can be differentiated into high purity CNS populations, and making available for the first time high purity human oligodendroglial lineage cells for research and therapy. He subsequently transplanted these cells into acute and chronic spinal cord injured adult rats, and demonstrated that the cells survived, differentiated into myelinating oligodendrocytes, and restored locomotor ability in paralyzed animals. In this manner he is comparing the regenerative efficacy of different hESC lines, as well as young and old passage hESC lines. He is also investigating the ability of transplanted hESC derivatives to migrate in the adult CNS following manipulation of the environment. Finally, he is conducting gene chip and other molecular analyses of hESCs and their derivatives to determine points of control during their differentiation, and the effects on hESC derivatives following exposure to the injured CNS.
|Research Centers||Reeve-Irvine Research Center|
|Sue and Bill Gross Stem Cell Research Center|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=4554|