MENU
AUG 30, 2016 8:00 AM PDT

Challenge toward Clinical Trial for Spinal Cord Injury using iPS Cell

Speaker

Abstract
In our previous preclinical studies, when neural stem progenitor cells (NS/PCs)-derived from hiPSCs were transplanted into mouse or non-human primate spinal cord injury (SCI) models, long-term restoration of motor function was induced without tumorigenicity, by selecting suitable hiPSCs-lines (Nori et al., 2011; Okano et al., 2013; Okano and Yamanaka, 2014). However, NS/PCs derived from certain iPSC-lines gave rise to late-onset tumorigenicity after transplantation (Tsuji et al., 2010; Nori et al., 2015). Here, to preclude these risks before clinical application, we developed molecular characterization of hiPSCs and hiPSC-derived NS/PCs together with transplantation to injured spinal cord of immune-deficient mice (Nori et al., 2015; Sugai et al., 2016). We investigated global methylation status of tumorigenic hiPSC-NS/PCs and found that aberrant hypermethylation of a tumor suppressor gene was induced along the passage. For addressing the safety issue, remnant immature cells or tumor-initiating cells should be removed or induced into more mature cell types to avoid adverse effects of hiPSC-NS/PC transplantation. Because Notch signaling plays a role in maintaining NS/PCs, we evaluated the effects of γ-secretase inhibitor (GSI) and found that pretreating hiPSC-NS/PCs with GSI promoted neuronal differentiation and maturation in vitro, and GSI pretreatment also reduced the overgrowth of transplanted hiPSC-NS/PCs and inhibited the deterioration of motor function in vivo (Okubo et al., 2016). Based on these findings, we are establishing methods of production, selection and transplantation of clinical grade NS/PCs stocks-derived from human iPSC stocks generated from HLA-homozygous super-donors by CiRA. We aim to commence clinical research (Phase I–IIa) trials for treatments of sub-acute phase SCI using hiPSCs-derived NS/PCs in the near future.
 

Show Resources
You May Also Like
NOV 16, 2022 7:00 PM PST
C.E. CREDITS
NOV 16, 2022 7:00 PM PST
Date: November 16, 2022 Time: 2:00pm (AEST) Date: November 17, 2022 7:00pm (PST), 10:00pm (EST), 4:00am (CET) The growth in FDA-approved cell and gene therapy products for the treatment of d...
OCT 11, 2022 8:00 AM PDT
C.E. CREDITS
OCT 11, 2022 8:00 AM PDT
Date: October 11, 2022 Time: 8:00am (PDT), 11:00pm (EDT), 5:00pm (CEST) Multiomic profiling of cell populations at single-cell resolution is revolutionizing scientists’ understanding o...
JUN 28, 2022 7:00 AM PDT
JUN 28, 2022 7:00 AM PDT
Date: June 28, 2022 Time: 3:00pm (BST), 4:00pm (CET), 9:00am (CST), 7am (PST) Light-sheet microscopy is an extremely versatile imaging technique with a vast range of implementations that are...
SEP 22, 2022 9:00 AM PDT
SEP 22, 2022 9:00 AM PDT
Date: September 22, 2022 Time: 9:00am (PDT), 12:00pm (EDT), 6:00pm (CEST) Optimizing platforms for surgical specimen collection and deep human phenotyping was used to enhance protein biomarke...
NOV 09, 2022 8:00 AM PST
C.E. CREDITS
NOV 09, 2022 8:00 AM PST
Date: November 09, 2022 Time: 8:00am (PST), 11:00am (EST), 5:00pm (CET) The field of cell and gene therapy is rapidly growing. In particular, the use of lentiviruses in CAR-T applications is...
NOV 01, 2022 10:00 AM PDT
NOV 01, 2022 10:00 AM PDT
Date: November 01, 2022 Time: 10:00am (PDT), 1:00pm (EDT), 6:00pm (CET) Our laboratory developed the Pig-a gene mutation assay as a means to simply and reliably evaluate the potential mutage...
Loading Comments...
Show Resources