Concise Review: Laying the Groundwork for a First-In-Human Study of an Induced Pluripotent Stem Cell-Based Intervention for Spinal Cord Injury

Abstract

There have been numerous attempts to develop stem cell transplantation approaches to promote the regeneration of spinal cord injury (SCI). Our multicenter team is currently planning to launch a first‐in‐human clinical study of an induced pluripotent stem cell (iPSC)‐based cell transplant intervention for subacute SCI. This trial was conducted as class I regenerative medicine protocol as provided for under Japan's Act on the Safety of Regenerative Medicine, using neural stem/progenitor cells derived from a clinical‐grade, integration‐free human “iPSC stock” generated by the Kyoto University Center for iPS Cell Research and Application. In the present article, we describe how we are preparing to initiate this clinical study, including addressing the issues of safety and tumorigenesis as well as practical problems that must be overcome to enable the development of therapeutic interventions for patients with chronic SCI. stem cells 2019;37:6–13

Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

“…Instead, a cascade of events take place, such as the formation of glial scar that prevents regeneration and results in neurodegeneration and cell death . Current clinical treatments are designed to pharmacologically improve the disease symptoms in combination with rehabilitation activities to restore physical function to some extent; however, no therapies are yet available to fully restore lost functions or slow ongoing neurodegeneration following the injury or disease . It has been recognized that the failure of neurons to regenerate is mostly due a damaged environment that does not support regeneration rather than characteristic features of the neurons themselves .…”

“…Advanced biomaterials can provide a structural platform to bridge the gap of damaged neural tissue, deliver stem cells to the site of injury, enable and augment the targeted delivery of therapeutic molecules, and help rebuild damaged circuits and repair damaged neuronal pathways. [106b,117] In a 2016 meta‐analysis of nonclinical studies using NSPC transplantation for spinal cord injury treatment, it was found that scaffold use in NSPC transplantation effectively increase functional recovery comparing to scaffold‐free cell suspension . The ideal materials for neural regeneration should be biocompatible with low immunogenicity, mechanocompatible to provide structural support to the surrounding neural tissue, and encourage stem cell survival, differentiation and integration with host cells.…”

“…The ideal materials for neural regeneration should be biocompatible with low immunogenicity, mechanocompatible to provide structural support to the surrounding neural tissue, and encourage stem cell survival, differentiation and integration with host cells. [106b,119] In this section, we highlight neuroregeneration in the brain, the spinal cord, and peripheral nerves ( Table 3 ) that utilized advanced biomaterial‐assisted stem cell delivery strategies to regenerate neural tissues.…”

Genomic research delivering on promises: From rejuvenation to vaccines and pharmacogenetics

“…Cell therapy though has made enormous progress in the forms of haematopoietic stem cell replacement, the only form of curative therapy for some forms of leukaemias, molecularly engineered T‐cell therapy, often curing patients who would have otherwise died prematurely, and induced pluripotent stem cells …”

The Challenge of Bringing iPSCs to the Patient

“…For spinal cord injuries, preclinical studies with iPSCs-neural progenitor cells in a non-human primate model provided evidence for remyelination and locomotor function recovery [68]. In February 2018, the Japan government gave the go-ahead to Professor Hideyuki Okano for a clinical trial aimed at treating patients with spinal cord injuries at Keio University (Tokyo) [53,69]. Conversely, in 2017, iPSC-derived cardiomyocytes were transplanted by Kawamura et al in a porcine model of ischemic cardiomyopathy using a cell-sheet technique.…”