title: Long-term efficacy and safety of human umbilical cord mesenchymal stromal cells in rotenone-induced hemiparkinsonian rats.
abstract: 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, and long-term efficacy of this approach. In this study, we investigated migration, therapeutic, tumorigenesis, and epileptogenic effects of human umbilical cord mesenchymal stromal cells (HUMSCs) 1 year after transplantation into rotenone-induced hemiparkinsonian rats. Our data indicated that DiI-labeled HUMSCs migrated in the lesioned hemisphere, from corpus striatum (CPu) to substantia nigra. By integrating with host cells and differentiating into NSE, GFAP, Nestin, and tyrosine hydroxylase-positive cells, HUMSCs prevented 48.4% dopamine neurons from degeneration and 56.9% dopamine terminals from loss, both correlating with improvement of apomorphine-induced rotations. The CD50 and CD97 value of pentylenetetrazol and semiquantitative immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), β-catenin, C-myc, and NF-κB expression showed no significant difference between HUMSCs transplanted and untransplanted groups, whereas the expressions of Bcl-2 and P53 in the grafted CPu were upregulated by 281% and 200% compared to ungrafted CPu. The results of this long-term study suggest that HUMSCs transplantation, 1 of the most potential treatments for Parkinson's disease, is an effective and safe approach.
authors.affiliation: Department of Neurology, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Nian
authors.initials: N
authors.lastname: Xiong
authors.forename: Xuebing
authors.initials: X
authors.lastname: Cao
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jinsha
authors.initials: J
authors.lastname: Huang
authors.forename: Chunnuan
authors.initials: C
authors.lastname: Chen
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.forename: Zhihou
authors.initials: Z
authors.lastname: Liang
authors.forename: Shenggang
authors.initials: S
authors.lastname: Sun
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lin
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002232:Carbocyanines / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000628:therapy*; D010433:Pentylenetetrazole / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D012402:Rotenone / Q000494:pharmacology*; D013194:Staining and Labeling / Q000379:methods; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology*; D017557:Ventral Tegmental Area / Q000166:cytology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002232:Carbocyanines; C510602:Grap protein, human; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D012402:Rotenone; C024286:3,3'-dioctadecylindocarbocyanine; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase; D001058:Apomorphine; D010433:Pentylenetetrazole