Alzheimer’s disease (AD) is the most devastating neurodegenerative disorder, and is characterized by progressive decline in cognitive functions. Degeneration of basal forebrain cholinergic neurons (BFCNs) is associated with cognitive impairments of AD, implying that BFCNs hold potentials in exploring stem cell-based replacement therapy for AD. However, studies on derivation of BFCNs from embryonic stem cells (ESCs) are limited, and the application of ESC-derived BFCNs remains to be determined.
Dr. JING Naihe’s group at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS) of the Chinese Academy of Sciences (CAS), reported that both mouse and human ESC-derived BFCNs could functionally integrate into the basal forebrain of AD mice, and ameliorate the cognitive symptoms associated with AD in mouse models.
We have developed differentiation approaches that direct both mouse and human ESCs into mature and functional BFCNs. The differentiation process recapitulates all key features of BFCN specification in vivo and goes through a BFCN-progenitor stage. These ESC-derived BFCNs exhibit features similar to those of their in vivo counterparts, and acquire appropriate functional properties in vitro. The ESC-derived BFCN progenitors are transplanted into the basal forebrain, where the in vivo BFCNs are situated, of transgenic AD mice. Two months later, the transplanted BFCN progenitors are found to predominantly differentiate into mature cholinergic neurons that functionally integrate into the endogenous basal forebrain cholinergic projection system of these AD mice. Furthermore, AD mice grafted with mouse or human BFCNs exhibit improvements in learning and memory performances. Our findings suggest the promising perspective of ESC-derived BFCNs in development of stem cell-based therapies for treatment of AD.
This study entitled “ESC-derived basal forebrain cholinergic neurons ameliorate the cognitive symptoms associated with Alzheimer’s disease in mouse models” has been done with help from Dr. SHU Yousheng from Beijing Normal University and Dr. YU Xiang from ION, SIBS, and has been published online in Stem Cell Reports on October 15.
This work was funded by the Ministry of Science and Technology of China, the National Natural Science Foundation of China, and the Chinese Academy of Sciences.
AUTHOR CONTACT:
YUE Chunmei and JING Naihe, From State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
320 Yue Yang Road, Shanghai 200031, China,
Tel.: +86-21-5492-1381;
Fax: +86-21-5492-1011;
E-mail: cmyue@sibcb.ac.cn, njing@sibcb.ac.cn.
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