test-THE APPROACH
We have devised a chemically defined culture system of neural differentiation, with which we can reveal the regulatory programs that guide the cell fate, and can get functional neurons and glia from pluripotent stem cells. Using clinical grade human embryonic stem cells, we can scale up the differentiation of varies types of functional human cells that can be used for therapy. These cells will be carefully assessed for satisfactory safety and efficacy, in particularly in mammalian or non-human primate models. We also develop tool sets to study the evolutionary innovation that cause the enlarged cortex and increased gyri. An in-depth understanding of this is particularly helpful to improve the production of desired cells from human pluripotent stem cells, so that the most appropriate types of cells can be used to treat neurological diseases such as Parkinson disease, Huntington disease or stroke. We optimize tools of gene editing, engineering and delivery for improved efficiency in human context, and employ lately developed cerebral organoids system to generate functional modules of human brain, with intention to promote earlier clinical application of these novel techniques.
THE INNOVATIONS AND DISCOVERIES
Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. We compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model. We found that the grafts did not form tumors and produced variable but apparent behavioral improvement for at least 24 months in most monkeys in both groups. In addition, a slight DA increase in the striatum correlates with significant functional improvement. These results demonstrated that clinical-grade hPESCs can serve as a reliable source of cells for PD treatment. Our proof-of-concept findings provide preclinical data for China's first ESC-based phase I/IIa clinical study of PD.
Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. We compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model. We found that the grafts did not form tumors and produced variable but apparent behavioral improvement for at least 24 months in most monkeys in both groups. In addition, a slight DA increase in the striatum correlates with significant functional improvement. These results demonstrated that clinical-grade hPESCs can serve as a reliable source of cells for PD treatment. Our proof-of-concept findings provide preclinical data for China's first ESC-based phase I/IIa clinical study of PD.
Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. We compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model. We found that the grafts did not form tumors and produced variable but apparent behavioral improvement for at least 24 months in most monkeys in both groups. In addition, a slight DA increase in the striatum correlates with significant functional improvement. These results demonstrated that clinical-grade hPESCs can serve as a reliable source of cells for PD treatment. Our proof-of-concept findings provide preclinical data for China's first ESC-based phase I/IIa clinical study of PD.
PUBLICATIONS
test-J. Wu*, D. Song*, Z. Li*, B. Guo*, Y. Xiao, W. Liu, L. Liang, C. Feng, T. Gao, Y. Chen, Y. Li, Z. Wang, J. Wen, S. Yang, P. Liu, L. Wang, Y. Wang; L. Peng, G. N Stacey, Z. Hu, G. Feng, W. Li, Y. Huo,; R. Jin, N. Shyh-Chang, Q. Zhou, L. Wang, B. Hu#, H. Dai#, J. Hao#, (2020), Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis. Cell Res, 30 (9): p. 794-809. DOI: 0.1038/s41422-020-0354-1 WOS: 000540666800001
test-J. Wu*, D. Song*, Z. Li*, B. Guo*, Y. Xiao, W. Liu, L. Liang, C. Feng, T. Gao, Y. Chen, Y. Li, Z. Wang, J. Wen, S. Yang, P. Liu, L. Wang, Y. Wang; L. Peng, G. N Stacey, Z. Hu, G. Feng, W. Li, Y. Huo,; R. Jin, N. Shyh-Chang, Q. Zhou, L. Wang, B. Hu#, H. Dai#, J. Hao#, (2020), Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis. Cell Res, 30 (9): p. 794-809. DOI: 0.1038/s41422-020-0354-1 WOS: 000540666800001
test-J. Wu*, D. Song*, Z. Li*, B. Guo*, Y. Xiao, W. Liu, L. Liang, C. Feng, T. Gao, Y. Chen, Y. Li, Z. Wang, J. Wen, S. Yang, P. Liu, L. Wang, Y. Wang; L. Peng, G. N Stacey, Z. Hu, G. Feng, W. Li, Y. Huo,; R. Jin, N. Shyh-Chang, Q. Zhou, L. Wang, B. Hu#, H. Dai#, J. Hao#, (2020), Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis. Cell Res, 30 (9): p. 794-809. DOI: 0.1038/s41422-020-0354-1 WOS: 000540666800001
test-J. Wu*, D. Song*, Z. Li*, B. Guo*, Y. Xiao, W. Liu, L. Liang, C. Feng, T. Gao, Y. Chen, Y. Li, Z. Wang, J. Wen, S. Yang, P. Liu, L. Wang, Y. Wang; L. Peng, G. N Stacey, Z. Hu, G. Feng, W. Li, Y. Huo,; R. Jin, N. Shyh-Chang, Q. Zhou, L. Wang, B. Hu#, H. Dai#, J. Hao#, (2020), Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis. Cell Res, 30 (9): p. 794-809. DOI: 0.1038/s41422-020-0354-1 WOS: 000540666800001
（+86）-010-64803745
iscr@ioz.ac.cn
Beijing 100101, P.R.China
Copyright:@Institute for Stem Cell and Regeneration, Chinese Academy of Sciences 备案号： 京ICP备05064604号-28