This project aims to develop a neural stem cell (NSC) therapy to repair the injured spinal cord and support functional recovery. In the proposed work, we aim to advance this program to an IND-enabling stage. Moreover, we aim to continue to develop and optimize potential stem cell therapies for spinal cord injury (SCI) by examining combinations of innovative rehabilitation and spinal cord neuromodulation strategies with neural stem cell therapies to potentially amplify stem cell-mediated recovery of function. Finally, we aim to invest substantial effort to assess NSC efficacy in chronic SCI. This work focuses on human NSCs derived from a federally ?approved? human embryonic stem cell (ESC) line, the H9 ESC line. The studies we propose herein will primarily use clinically relevant spinal cord injury contusion models. Independent replication by an investigator outside this consortium of scientists will be conducted. Notably, this is an intensely collaborative effort among leading laboratories researching spinal cord injury, including the Tuszynski group at the San Diego VA Medical Center and UCSD (includes Drs. Rosenzweig, Lu and Brock); the Beattie/Bresnahan/Ferguson group at the San Francisco VA Medical Center and UCSF; the Reinkensmeyer lab at UC Irvine; the Havton lab at UCLA; the California National Primate Research Center located at UC Davis; and the Courtine lab at the Swiss Federal Institute of Technology. Experiments have been collectively designed and performed by this consortium, an unprecedented effort in SCI research to advance the field through close collaboration and interaction on jointly performed experiments. Throughout, this project will benefit from a free exchange of information among the collaborators.
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, and neuromodulation strategies to amplify stem cell-mediated recovery of function.
|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|