Long-Term Efficacy and Safety of Human Umbilical Cord Mesenchymal Stromal Cells in Rotenone-Induced Hemiparkinsonian Rats

作者: Nian Xiong , Xuebing Cao , Zhentao Zhang , Jinsha Huang , Chunnuan Chen

DOI: 10.1016/J.BBMT.2010.06.004

关键词:

摘要: Several studies have shown functional improvements, neuroprotective, and neuroregenerative effects after mesenchymal stem cells transplantation to parkinsonian animal models. However, questions remain about the safety, feasibility, long-term efficacy of this approach. In study, we investigated migration, therapeutic, tumorigenesis, epileptogenic human umbilical cord stromal (HUMSCs) 1 year into rotenone-induced hemiparkinsonian rats. Our data indicated that DiI-labeled HUMSCs migrated in lesioned hemisphere, from corpus striatum (CPu) substantia nigra. By integrating with host differentiating NSE, GFAP, Nestin, tyrosine hydroxylase-positive cells, prevented 48.4% dopamine neurons degeneration 56.9% terminals loss, both correlating improvement apomorphine-induced rotations. The CD50 CD97 value pentylenetetrazol semiquantitative immunohistochemical analysis proliferating cell nuclear antigen (PCNA), β-catenin, C-myc, NF-κB expression showed no significant difference between transplanted untransplanted groups, whereas expressions Bcl-2 P53 grafted CPu were upregulated by 281% 200% compared ungrafted CPu. results study suggest transplantation, most potential treatments for Parkinson's disease, is an effective safe

参考文章(59)
M.A. Hellmann, H. Panet, Y. Barhum, E. Melamed, D. Offen, Increased survival and migration of engrafted mesenchymal bone marrow stem cells in 6-hydroxydopamine-lesioned rodents Neuroscience Letters. ,vol. 395, pp. 124- 128 ,(2006) , 10.1016/J.NEULET.2005.10.097
Anke Brederlau, Ana Sofia Correia, Sergey V. Anisimov, Muna Elmi, Gesine Paul, Laurent Roybon, Asuka Morizane, Filip Bergquist, Ilse Riebe, Ulf Nannmark, Manolo Carta, Erik Hanse, Jun Takahashi, Yoshiki Sasai, Keiko Funa, Patrick Brundin, Peter S. Eriksson, Jia-Yi Li, Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: effect of in vitro differentiation on graft survival and teratoma formation. Stem Cells. ,vol. 24, pp. 1433- 1440 ,(2006) , 10.1634/STEMCELLS.2005-0393
Yu-Show Fu, Yun-Chih Cheng, Maan-Yuh Anya Lin, Henrich Cheng, Pei-Ming Chu, Shih-Chich Chou, Yang-Hsin Shih, Miau-Hwa Ko, Min-Shan Sung, Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells. ,vol. 24, pp. 115- 124 ,(2006) , 10.1634/STEMCELLS.2005-0053
Amy J Wagers, Richard I Sherwood, Julie L Christensen, Irving L Weissman, Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells Science. ,vol. 297, pp. 2256- 2259 ,(2002) , 10.1126/SCIENCE.1074807
L. Velisek, H. Kubova, M. Pohl, L. Stankova, P. Mareš, R. Schickerova, Pentylenetetrazol-induced seizures in rats: an ontogenetic study. Naunyn-schmiedebergs Archives of Pharmacology. ,vol. 346, pp. 588- 591 ,(1992) , 10.1007/BF00169017
G. C. Kopen, D. J. Prockop, D. G. Phinney, Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains Proceedings of the National Academy of Sciences of the United States of America. ,vol. 96, pp. 10711- 10716 ,(1999) , 10.1073/PNAS.96.19.10711
P. Bossolasco, L. Cova, C. Calzarossa, S.G. Rimoldi, C. Borsotti, G. Lambertenghi Deliliers, V. Silani, D. Soligo, E. Polli, Neuro-glial differentiation of human bone marrow stem cells in vitro Experimental Neurology. ,vol. 193, pp. 312- 325 ,(2005) , 10.1016/J.EXPNEUROL.2004.12.013
Rohita Sharma, Catherine R. McMillan, Lennard P. Niles, Neural stem cell transplantation and melatonin treatment in a 6-hydroxydopamine model of Parkinson's disease. Journal of Pineal Research. ,vol. 43, pp. 245- 254 ,(2007) , 10.1111/J.1600-079X.2007.00469.X
Ron Firestein, Adam J. Bass, So Young Kim, Ian F. Dunn, Serena J. Silver, Isil Guney, Ellen Freed, Azra H. Ligon, Natalie Vena, Shuji Ogino, Milan G. Chheda, Pablo Tamayo, Stephen Finn, Yashaswi Shrestha, Jesse S. Boehm, Supriya Jain, Emeric Bojarski, Craig Mermel, Jordi Barretina, Jennifer A. Chan, Jose Baselga, Josep Tabernero, David E. Root, Charles S. Fuchs, Massimo Loda, Ramesh A. Shivdasani, Matthew Meyerson, William C. Hahn, CDK8 is a colorectal cancer oncogene that regulates β-catenin activity Nature. ,vol. 455, pp. 547- 551 ,(2008) , 10.1038/NATURE07179