title: Transplanted motoneurons derived from human induced pluripotent stem cells form functional connections with target muscle.
abstract: Induced pluripotent stem cells (iPSCs) hold promise for the treatment of motoneuron diseases because of their distinct features including pluripotency, self-derivation and potential ability to differentiate into motoneurons. However, it is still unknown whether human iPSC-derived motoneurons can functionally innervate target muscles in vivo, which is the definitive sign of successful cell therapy for motoneuron diseases. In the present study, we demonstrated that human iPSCs derived from mesenchymal cells of the umbilical cord possessed a high yield in neural differentiation. Using a chemically-defined in vitro system, human iPSCs efficiently differentiated into motoneurons which displayed typical morphology, expressed specific molecules, and generated repetitive trains of action potentials. When transplanted into the injured musculocutaneous nerve of rats, they survived robustly, extended axons along the nerve, and formed functional connections with the target muscle (biceps brachii), thereby protecting the muscle from atrophy. Our study provides evidence for the first time that human iPSC-derived motoneurons are truly functional not only in vitro but also in vivo, and they have potential for stem cell-based therapies for motoneuron diseases.
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.forename: Jinglei
authors.initials: J
authors.lastname: Cai
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Yuan
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yao
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Wong
authors.forename: Wenhao
authors.initials: W
authors.lastname: Huang
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wan
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.forename: Dajiang
authors.initials: D
authors.lastname: Qin
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016472:Motor Neuron Disease / Q000628:therapy*; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000294:innervation*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley