title: Umbilical cord-derived mesenchymal stem cell therapy for neurological disorders via inhibition of mitogen-activated protein kinase pathway-mediated apoptosis.
abstract: The present study investigated the recovery and intrathecal administration of human umbilical cord‑derived mesenchymal stem cells (HUC‑MSCs) by lumbar puncture and analyzed the technical difficulties and short and long‑term effects of UC‑MSC transplantation in various neurological conditions. In total, 100 patients who underwent subarachnoid placement of UC‑MSCs between December 2006 and May 2010 were included in the present study. The present study evaluated the number of attempts, localization of subarachnoid space and postprocedural complications. The Hauser Ambulation Index was employed for functional assessment. Clinical symptoms, the associated biochemical index and photographic examinations were observed regularly. HUC‑MSCs were transplanted into mice as well as patients in order to determine the underlying therapeutic mechanisms. Technical difficulties were encountered in 31 patients (31%) in the form of general anesthesia supplementation and difficulty localizing lumbar space. Side effects were observed in 22 (22%) patients, which resolved with symptomatic treatment within 48 h. On follow‑up one year later, functional indices improved in 47 (47%) patients. Transplantation of HUC‑MSCs inhibited apoptosis and the protein expression of c-Jun N-terminal kinase and p38 as well as triggered the phosphorylation of P‑42/44 extracellular-signal-regulated kinase. In conclusion, intrathecal administration of UC‑MSCs is safe and effective with no long‑term adverse effects in neurological disorders. HUC‑MSCs may achieve these effects via the mitogen‑activated protein kinase pathway. The results suggest that there is a promise of restoration of lost tissue and improvement of function in patients with profound neurological defects. These data support expanded double blind, placebo‑controlled studies for this treatment modality.
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Huaihong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D064987:Cell- and Tissue-Based Therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008875:Middle Aged; D009422:Nervous System Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000628:therapy; D016896:Treatment Outcome; D014470:Umbilical Cord / Q000166:cytology*; D055815:Young Adult