One Step at a Time, Stem Cell Therapy for Traumatic Brain Injury Needs Two More Breakthroughs

Abstract

26As of 2015, a total of 49 ALS patients have received NSI-566 cells. Both the cells and surgery were well tolerated and the ALS studies reported a 47% responder rate with decline in disease progression and improved grip strength. Stem cells inc., on the other hand lost a patent dispute to NSI and recently closed operations.J Stem Cell Res Ther. 2016;1(4):160-164. 160© 2016 Shyam. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially.One step at a time, stem cell therapy for traumatic brain injury needs two more breakthroughs Step 2 ImmunosuppressionTransplantation of the cells conferred benefits such as restoration of injured neuronal morphology 45 and cognitive function. 46 even without immunosuppression. Transient immunosuppression was shown to be sufficient to support engraftment and transplanted derived neurons were reportedly present 6 months post transplantation. 47 However, no data quantifying either engraftment or behavior modification were presented. Such studies were limited by cyclosporine mediated immunosuppression which resulted in persistence of barriers to engraftment and demonstration of effectiveness of the approach. 48-50The initial optimism was replaced by skepticism if the therapeutic potential of neural stem cells: greater in people's perception than in their brains. 51,52 The US Food and Drug Administration (FDA; Rockville, MD) guidelines on preclinical assessment of cell therapies in the publication "Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products".53,54 A review of literature shows human cell therapy in rat TBI that measure cognitive benefit have not addressed donor cell fate past one-month posttransplantation. 1,55 Further the experts in the field recommended that 8-week survival period prior to assessments would allow sufficient time for differentiation and integration of human neural stem cells with the host and possibly validate the presumed mechanism of action. 1,26The successful preclinical ALS, SCI and stroke studies. 40,41,44,56 have employed a different immunosuppression technique that was pioneered by Hefferan et al. 40 This technique relies on three agents namely: mycophenylate mofetil, tacrolimus and methyl prednisolone. The combination has been found to be superior to cyclosporine, a standard immunosuppressant between 1999-2012. Step 3 Mechanism of actionHowever, due to the lack of exact mechanism of action still precludes attempts to move neural stem cell therapy to the clinic. 26Paul Lu et al. 41 demonstrated the mechanism of regeneration in spinal cord injury models. 41 Axonal growth was partially dependent on mammalian target of rapamycin (mTOR), but not Nogo signaling. Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery. The recovery was lost subsequent to re-transection of the spinal cord....