The project aims to develop a stem cell-based therapy to repair the chronically injured spinal cord and to maximize functional recovery. Success development of this work can lead to translation of pre-clinical observations from animal models into clinical practice. Moreover, we aim to develop innovative rehabilitation strategies to promote meaningful recovery of function, and objectively determine whether a combination of stem cell-based therapies with rehabilitation will optimize functional outcomes. We will focus on multipotent neural progenitor cells derived from approved embryonic stem cell lines, and on multipotent neural stem /progenitor cells directly transdifferentiated from adult fibroblasts (a form of Induced Pluripotent Stem Cell, IPSC). The work will use both transection and contusion models of spinal cord injury in rodent and non-human primate species. Moreover, we propose replication studies by an investigator that is independent of the consortium of scientists in this project. This is an intensely collaborative effort among leading laboratories researching spinal cord injury located on the west coast of the United States, including the Tuszynski group at the San Diego VA Medical Center and UCSD; the Beattie/Bresnahan group at the San Francisco VA Medical Center and UCSF; the Edgerton group at UCLA; the Havton and Rinkensmeyer groups at UC Irvine; and the California Regional Primate Research Center located at UC Davis. Proposed experiments are collectively designed and performed by this collaboration, an unprecedented effort in spinal cord injury research to move the field forward through close collaboration and interaction on jointly performed experiments. Throughout, this project will benefit from a free exchange of information among the collaborators.

Public Health Relevance

Numerous veterans are living with spinal cord injury. The project will fund a consortium of leading spinal cord injury researchers to work collaboratively to develop therapies to repair the chronically injured spinal cord and to maximize functional recovery. Research will focus on the promising biology of stem cells to replace lost cells and form new neural circuits, in combination with rehabilitation strategies to train the spinal cord to use the new circuits.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (I50)
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Centers, Research Enhancement Award Program and Consortiums (RRDC)
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VA San Diego Healthcare System
San Diego
United States
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Adler, Andrew F; Lee-Kubli, Corinne; Kumamaru, Hiromi et al. (2017) Comprehensive Monosynaptic Rabies Virus Mapping of Host Connectivity with Neural Progenitor Grafts after Spinal Cord Injury. Stem Cell Reports 8:1525-1533
Lu, Paul; Ceto, Steven; Wang, Yaozhi et al. (2017) Prolonged human neural stem cell maturation supports recovery in injured rodent CNS. J Clin Invest 127:3287-3299
Kadoya, Ken; Lu, Paul; Nguyen, Kenny et al. (2016) Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat Med 22:479-87