Long-term efficacy and safety of human umbilical cord mesenchymal stromal cells in rotenone-induced hemiparkinsonian rats.
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.
Xiong
Nian
N
Department of Neurology, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Cao
Xuebing
X
Zhang
Zhentao
Z
Huang
Jinsha
J
Chen
Chunnuan
C
Zhang
Zhaowen
Z
Jia
Min
M
Xiong
Jing
J
Liang
Zhihou
Z
Sun
Shenggang
S
Lin
Zhicheng
Z
Wang
Tao
T
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
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