Umbilical cord-derived mesenchymal stem cell therapy for neurological disorders via inhibition of mitogen-activated
protein kinase pathway-mediated apoptosis

Zhang,Ruoyu; Chen,Huaihong; Zheng,Zhe; Liu,Qiang; Xu,Lei

doi:10.3892/mmr.2014.2985

March-2015 Volume 11 Issue 3

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March-2015 Volume 11 Issue 3

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Article

Umbilical cord-derived mesenchymal stem cell therapy for neurological disorders via inhibition of mitogen-activated protein kinase pathway-mediated apoptosis

Authors:
- Ruoyu Zhang
- Huaihong Chen
- Zhe Zheng
- Qiang Liu
- Lei Xu
View Affiliations / Copyright

Affiliations: Department of Geriatrics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
Pages: 1807-1812
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Published online on: November 19, 2014

https://doi.org/10.3892/mmr.2014.2985
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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.

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1	Wang L, et al: Protective effect of transplanted bone marrow-derived mesenchymal stem cells on pancreatitis-associated lung injury in rats. Mol Med Rep. 6:287–292. 2012.PubMed/NCBI
2	Trivanović D, Kocić J, Mojsilović S, et al: Mesenchymal stem cells isolated from peripheral blood and umbilical cord Wharton’s jelly. Srp Arh Celok Lek. 41:178–186. 2013. View Article : Google Scholar
3	Titomanlio L, et al: Stem cell therapy for neonatal brain injury: perspectives and challenges. Ann Neurol. 70:698–712. 2011. View Article : Google Scholar : PubMed/NCBI
4	Liu J, Han D, Wang Z, et al: Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells. Cytotherapy. 15:185–191. 2013. View Article : Google Scholar : PubMed/NCBI
5	Wang L, Ji H, Zhou J, et al: Therapeutic potential of umbilical cord mesenchymal stromal cells transplantation for cerebral palsy: a case report. Case Rep Transplant. 2013:1463472013.PubMed/NCBI
6	O’Hare E and Young PJ: Childhood spinal muscular atrophy and stem cell research: Is cellular replacement therapy the answer? (Review). Mol Med Rep. 2:3–5. 2009.
7	Lim JY, Jeong CH, et al: Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia. Stem Cell Res Ther. 2:382011. View Article : Google Scholar : PubMed/NCBI
8	Kang EJ, Lee YH, Kim MJ, et al: Transplantation of porcine umbilical cord matrix mesenchymal stem cells in a mouse model of Parkinson’s disease. J Tissue Eng Regen Med. 7:169–182. 2013. View Article : Google Scholar
9	Zhang XJ, Luan ZG and Ma XC: shRNAs targeting high-mobility group box-1 inhibit E-selectin expression via homeobox A9 in human umbilical vein endothelial cells. Mol Med Rep. 7:1251–1256. 2013.PubMed/NCBI
10	Gu Z, Akiyama K, Ma X, et al: Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice. Lupus. 19:1502–1514. 2010. View Article : Google Scholar : PubMed/NCBI
11	Hauser SL, Dawson DM, et al: Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med. 308:173–180. 1983. View Article : Google Scholar : PubMed/NCBI
12	Dalous J, Larghero J and Baud O: Transplantation of umbilical cord-derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perpectives. Pediatr Res. 71:482–490. 2012. View Article : Google Scholar : PubMed/NCBI
13	Glass JD, Boulis NM, et al: Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients. Stem Cells. 30:1144–1151. 2012. View Article : Google Scholar : PubMed/NCBI
14	Wang H, Yang Y, et al: Programming of human umbilical cord mesenchymal stem cells in vitro to promote pancreatic gene expression. Mol Med Rep. 8:769–774. 2013.PubMed/NCBI
15	Lepore AC: Intraspinal cell transplantation for targeting cervical ventral horn in amyotrophic lateral sclerosis and traumatic spinal cord injury. J Vis Exp. Sep 18–2011. View Article : Google Scholar : PubMed/NCBI
16	Wiley CA and Achim C: Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome. Ann Neurol. 36:673–676. 1994. View Article : Google Scholar : PubMed/NCBI
17	Xu W, et al: Chitooligosaccharides and N-acetyl-D-glucosamine stimulate peripheral blood mononuclear cell-mediated antitumor immune responses. Mol Med Rep. 6:385–390. 2012.PubMed/NCBI
18	Ciardi A, et al: The involvement of the cerebral cortex in human immunodeficiency virus encephalopathy: a morphological and immunohistochemical study. Acta Neuropathol. 81:51–59. 1990. View Article : Google Scholar : PubMed/NCBI
19	Cursio R, Gugenheim J, Ricci JE, et al: A caspase inhibitor fully protects rats against lethal normothermic liver ischemia by inhibition of liver apoptosis. FASEB J. 13:253–261. 1999.PubMed/NCBI