Therapeutic effects of intranigral transplantation of mesenchymal stem cells in rat models of Parkinson's disease

Stem cell transplantation is a promising tool for the treatment of neurodegenerative disorders, including Parkinson's disease (PD); however, the therapeutic routes and mechanisms of mechanical approaches to stem cell transplantation must be explored. This study tests the therapeutic effect of t...

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Veröffentlicht in:Journal of neuroscience research 2017-03, Vol.95 (3), p.907-917
Hauptverfasser: Chen, Dandan, Fu, Wenyu, Zhuang, Wenxin, Lv, Cui, Li, Fengjie, Wang, Xin
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container_issue 3
container_start_page 907
container_title Journal of neuroscience research
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creator Chen, Dandan
Fu, Wenyu
Zhuang, Wenxin
Lv, Cui
Li, Fengjie
Wang, Xin
description Stem cell transplantation is a promising tool for the treatment of neurodegenerative disorders, including Parkinson's disease (PD); however, the therapeutic routes and mechanisms of mechanical approaches to stem cell transplantation must be explored. This study tests the therapeutic effect of transplantation of rat bone marrow mesenchymal stem cells (MSCs) into the substantia nigra (SN) of the PD rat. 5‐Bromo‐2‐deoxyuridine‐labeled rat MSCs were transplanted into the SN of the 6‐hydroxydopamine‐injected side of PD rat brains. The behavioral changes in PD rats were examined before and 4 and 8 weeks after MSC transplantation. The expression of tyrosine hydroxylase (TH) in the SN and the striatum and the survival and differentiation of MSCs were assessed by immunohistochemical and double immunofluorescence techniques. Abnormal behavior of PD rats was significantly improved by the administration of bone marrow MSCs, and the number of TH‐positive cells in the SN and the optical density of TH‐positive fibers in the striatum were markedly increased. Transplanted MSCs can survive and migrate in the brain and differentiate into nestin‐, neuron‐specific enolase‐, and GFAP‐positive cells. Our findings suggest that transplantation of rat bone marrow MSCs into the SN of PD rats may provide therapeutic effects. © 2016 Wiley Periodicals, Inc. The rat bone marrow mesenchymal stem cells (MSCs) were isolated, cultured and passaged, and then their neural differentiation potentials were identified by immunocytochemistry. After the MSCs were labeled by 5‐bromo‐2‐deoxyuridine (BrdU), the Brdu‐labeled cells were injected into substantia nigra of the 6‐OHDA‐injected side at one point of the rats of Parkinson's disease (PD). The rotational behavior of the PD rats in each group before and after transplant was evaluated by apomorphine intraperitoneal injection. The tyrosine hydroxylase (TH)‐immunoreactive cells and fibers in the substantia nigra and the striatum were calculated, and the survival, migration and differentiation of the implanted MSCs in vivo were examined.
doi_str_mv 10.1002/jnr.23879
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This study tests the therapeutic effect of transplantation of rat bone marrow mesenchymal stem cells (MSCs) into the substantia nigra (SN) of the PD rat. 5‐Bromo‐2‐deoxyuridine‐labeled rat MSCs were transplanted into the SN of the 6‐hydroxydopamine‐injected side of PD rat brains. The behavioral changes in PD rats were examined before and 4 and 8 weeks after MSC transplantation. The expression of tyrosine hydroxylase (TH) in the SN and the striatum and the survival and differentiation of MSCs were assessed by immunohistochemical and double immunofluorescence techniques. Abnormal behavior of PD rats was significantly improved by the administration of bone marrow MSCs, and the number of TH‐positive cells in the SN and the optical density of TH‐positive fibers in the striatum were markedly increased. Transplanted MSCs can survive and migrate in the brain and differentiate into nestin‐, neuron‐specific enolase‐, and GFAP‐positive cells. Our findings suggest that transplantation of rat bone marrow MSCs into the SN of PD rats may provide therapeutic effects. © 2016 Wiley Periodicals, Inc. The rat bone marrow mesenchymal stem cells (MSCs) were isolated, cultured and passaged, and then their neural differentiation potentials were identified by immunocytochemistry. After the MSCs were labeled by 5‐bromo‐2‐deoxyuridine (BrdU), the Brdu‐labeled cells were injected into substantia nigra of the 6‐OHDA‐injected side at one point of the rats of Parkinson's disease (PD). The rotational behavior of the PD rats in each group before and after transplant was evaluated by apomorphine intraperitoneal injection. The tyrosine hydroxylase (TH)‐immunoreactive cells and fibers in the substantia nigra and the striatum were calculated, and the survival, migration and differentiation of the implanted MSCs in vivo were examined.</description><identifier>ISSN: 0360-4012</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.23879</identifier><identifier>PMID: 27617772</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>6‐hydroxydopamine ; Animals ; Antigens, CD - metabolism ; bone marrow‐derived mesenchymal stem cells ; Bromodeoxyuridine - metabolism ; Cell Differentiation - physiology ; Cell Movement ; differentiation ; Disease Models, Animal ; Glial Fibrillary Acidic Protein - metabolism ; intranigral transplantation ; Male ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stromal Cells - physiology ; Microtubule-Associated Proteins - metabolism ; Nerve Fibers - metabolism ; Nestin - metabolism ; Oxidopamine - toxicity ; Parkinson Disease, Secondary - chemically induced ; Parkinson Disease, Secondary - surgery ; Parkinson's disease ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra - surgery ; Sympatholytics - toxicity ; Treatment Outcome ; Tyrosine 3-Monooxygenase - metabolism</subject><ispartof>Journal of neuroscience research, 2017-03, Vol.95 (3), p.907-917</ispartof><rights>2016 Wiley Periodicals, Inc.</rights><rights>2017 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3869-42222b831053db92968b81709f4f0b3f8113493514b9325330361c41128b1af63</citedby><cites>FETCH-LOGICAL-c3869-42222b831053db92968b81709f4f0b3f8113493514b9325330361c41128b1af63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjnr.23879$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjnr.23879$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27617772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Dandan</creatorcontrib><creatorcontrib>Fu, Wenyu</creatorcontrib><creatorcontrib>Zhuang, Wenxin</creatorcontrib><creatorcontrib>Lv, Cui</creatorcontrib><creatorcontrib>Li, Fengjie</creatorcontrib><creatorcontrib>Wang, Xin</creatorcontrib><title>Therapeutic effects of intranigral transplantation of mesenchymal stem cells in rat models of Parkinson's disease</title><title>Journal of neuroscience research</title><addtitle>J Neurosci Res</addtitle><description>Stem cell transplantation is a promising tool for the treatment of neurodegenerative disorders, including Parkinson's disease (PD); however, the therapeutic routes and mechanisms of mechanical approaches to stem cell transplantation must be explored. 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however, the therapeutic routes and mechanisms of mechanical approaches to stem cell transplantation must be explored. This study tests the therapeutic effect of transplantation of rat bone marrow mesenchymal stem cells (MSCs) into the substantia nigra (SN) of the PD rat. 5‐Bromo‐2‐deoxyuridine‐labeled rat MSCs were transplanted into the SN of the 6‐hydroxydopamine‐injected side of PD rat brains. The behavioral changes in PD rats were examined before and 4 and 8 weeks after MSC transplantation. The expression of tyrosine hydroxylase (TH) in the SN and the striatum and the survival and differentiation of MSCs were assessed by immunohistochemical and double immunofluorescence techniques. Abnormal behavior of PD rats was significantly improved by the administration of bone marrow MSCs, and the number of TH‐positive cells in the SN and the optical density of TH‐positive fibers in the striatum were markedly increased. Transplanted MSCs can survive and migrate in the brain and differentiate into nestin‐, neuron‐specific enolase‐, and GFAP‐positive cells. Our findings suggest that transplantation of rat bone marrow MSCs into the SN of PD rats may provide therapeutic effects. © 2016 Wiley Periodicals, Inc. The rat bone marrow mesenchymal stem cells (MSCs) were isolated, cultured and passaged, and then their neural differentiation potentials were identified by immunocytochemistry. After the MSCs were labeled by 5‐bromo‐2‐deoxyuridine (BrdU), the Brdu‐labeled cells were injected into substantia nigra of the 6‐OHDA‐injected side at one point of the rats of Parkinson's disease (PD). The rotational behavior of the PD rats in each group before and after transplant was evaluated by apomorphine intraperitoneal injection. The tyrosine hydroxylase (TH)‐immunoreactive cells and fibers in the substantia nigra and the striatum were calculated, and the survival, migration and differentiation of the implanted MSCs in vivo were examined.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>27617772</pmid><doi>10.1002/jnr.23879</doi><tpages>11</tpages></addata></record>
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subjects 6‐hydroxydopamine
Animals
Antigens, CD - metabolism
bone marrow‐derived mesenchymal stem cells
Bromodeoxyuridine - metabolism
Cell Differentiation - physiology
Cell Movement
differentiation
Disease Models, Animal
Glial Fibrillary Acidic Protein - metabolism
intranigral transplantation
Male
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal Stromal Cells - physiology
Microtubule-Associated Proteins - metabolism
Nerve Fibers - metabolism
Nestin - metabolism
Oxidopamine - toxicity
Parkinson Disease, Secondary - chemically induced
Parkinson Disease, Secondary - surgery
Parkinson's disease
Rats
Rats, Sprague-Dawley
Substantia Nigra - surgery
Sympatholytics - toxicity
Treatment Outcome
Tyrosine 3-Monooxygenase - metabolism
title Therapeutic effects of intranigral transplantation of mesenchymal stem cells in rat models of Parkinson's disease
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