The original objective of this study was to determine whether grafts of human NSCs to sites of SCI was safe, effective and worthy of human translation. We found that the lead candidate cell line, the UCSF4-NSC line, did not exhibit adequate long-term in vivo safety properties. However, an alternative cell line, the H9-NSC line, does exhibit favorable safety. We also identified for the first time that human NSCs exhibit a very prolonged, human temporal course of maturation in vivo, a finding with great implications for the design and performance of human clinical trials of NSCs for any neurological indication. Finally, we developed extremely important methods for the practical implementation of NSC transplantation to SCI lesion sites in humans.
While this specific program proposing to develop the UCSF4-NSC cell line for SCI will not move forward into patients, we are solidly on track for translating the H9-NSC line to potential human clinical trials. Moving forward, we propose to repeat several of the studies conducted in the Early Translational Award with the superior H9-NSC line. Studies funded during this Early Translational Award were essential in enabling the discoveries and insights that are propelling this program forward in a modified direction compared to the original proposal. We await review of a submitted TRAN1 grant proposal to determine whether this promising work will indeed continue. We are grateful to the dedicated staff at CIRM, and to the citizens of the State of California, for enabling and funding this work.