Cell-Based Therapy for Canavan Disease Using Human iPSC-Derived NPCs and OPCs
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Cell-Based Therapy for Canavan Disease Using Human iPSC-Derived NPCs and OPCs. / Feng, Lizhao; Chao, Jianfei; Tian, E.; Li, Li; Ye, Peng; Zhang, Mi; Chen, Xianwei; Cui, Qi; Sun, Guihua; Zhou, Tao; Felix, Gerardo; Qin, Yue; Li, Wendong; Meza, Edward David; Klein, Jeremy; Ghoda, Lucy; Hu, Weidong; Luo, Yonglun; Dang, Wei; Hsu, David; Gold, Joseph; Goldman, Steven A.; Matalon, Reuben; Shi, Yanhong.
In: Advanced Science, Vol. 7, No. 23, 2002155, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Cell-Based Therapy for Canavan Disease Using Human iPSC-Derived NPCs and OPCs
AU - Feng, Lizhao
AU - Chao, Jianfei
AU - Tian, E.
AU - Li, Li
AU - Ye, Peng
AU - Zhang, Mi
AU - Chen, Xianwei
AU - Cui, Qi
AU - Sun, Guihua
AU - Zhou, Tao
AU - Felix, Gerardo
AU - Qin, Yue
AU - Li, Wendong
AU - Meza, Edward David
AU - Klein, Jeremy
AU - Ghoda, Lucy
AU - Hu, Weidong
AU - Luo, Yonglun
AU - Dang, Wei
AU - Hsu, David
AU - Gold, Joseph
AU - Goldman, Steven A.
AU - Matalon, Reuben
AU - Shi, Yanhong
PY - 2020
Y1 - 2020
N2 - Canavan disease (CD) is a fatal leukodystrophy caused by mutation of the aspartoacylase (ASPA) gene, which leads to deficiency in ASPA activity, accumulation of the substrate N-acetyl-L-aspartate (NAA), demyelination, and spongy degeneration of the brain. There is neither a cure nor a standard treatment for this disease. In this study, human induced pluripotent stem cell (iPSC)-based cell therapy is developed for CD. A functional ASPA gene is introduced into patient iPSC-derived neural progenitor cells (iNPCs) or oligodendrocyte progenitor cells (iOPCs) via lentiviral transduction or TALEN-mediated genetic engineering to generate ASPA iNPC or ASPA iOPC. After stereotactic transplantation into a CD (Nur7) mouse model, the engrafted cells are able to rescue major pathological features of CD, including deficient ASPA activity, elevated NAA levels, extensive vacuolation, defective myelination, and motor function deficits, in a robust and sustainable manner. Moreover, the transplanted mice exhibit much prolonged survival. These genetically engineered patient iPSC-derived cellular products are promising cell therapies for CD. This study has the potential to bring effective cell therapies, for the first time, to Canavan disease children who have no treatment options. The approach established in this study can also benefit many other children who have deadly genetic diseases that have no cure.
AB - Canavan disease (CD) is a fatal leukodystrophy caused by mutation of the aspartoacylase (ASPA) gene, which leads to deficiency in ASPA activity, accumulation of the substrate N-acetyl-L-aspartate (NAA), demyelination, and spongy degeneration of the brain. There is neither a cure nor a standard treatment for this disease. In this study, human induced pluripotent stem cell (iPSC)-based cell therapy is developed for CD. A functional ASPA gene is introduced into patient iPSC-derived neural progenitor cells (iNPCs) or oligodendrocyte progenitor cells (iOPCs) via lentiviral transduction or TALEN-mediated genetic engineering to generate ASPA iNPC or ASPA iOPC. After stereotactic transplantation into a CD (Nur7) mouse model, the engrafted cells are able to rescue major pathological features of CD, including deficient ASPA activity, elevated NAA levels, extensive vacuolation, defective myelination, and motor function deficits, in a robust and sustainable manner. Moreover, the transplanted mice exhibit much prolonged survival. These genetically engineered patient iPSC-derived cellular products are promising cell therapies for CD. This study has the potential to bring effective cell therapies, for the first time, to Canavan disease children who have no treatment options. The approach established in this study can also benefit many other children who have deadly genetic diseases that have no cure.
KW - Canavan disease
KW - iPSCs
KW - leukodystrophy
KW - neural progenitor cells (NPCs)
KW - neurological diseases
KW - oligodendrocyte progenitor cells (OPCs)
KW - stem cell therapy
U2 - 10.1002/advs.202002155
DO - 10.1002/advs.202002155
M3 - Journal article
C2 - 33304759
AN - SCOPUS:85094190118
VL - 7
JO - Advanced Science
JF - Advanced Science
SN - 2198-3844
IS - 23
M1 - 2002155
ER -
ID: 251303980