Epidermal neural crest stem cell transplantation as a promising therapeutic strategy for ischemic stroke

被引:49
作者
Salehi, Mohammad Saied [1 ]
Pandamooz, Sareh [2 ]
Safari, Anahid [3 ]
Jurek, Benjamin [4 ]
Tamadon, Amin [5 ]
Namavar, Mohammad Reza [1 ]
Dianatpour, Mehdi [3 ]
Dargahi, Leila [2 ]
Azarpira, Negar [6 ]
Fattahi, Sadegh [7 ]
Moosavi, Seyed Mostafa Shid [8 ]
Keshavarz, Somaye [8 ]
Khodabandeh, Zahra [3 ]
Zare, Shahrokh [3 ]
Nazari, Somayeh [8 ]
Heidari, Mojdeh [6 ]
Izadi, Sadegh [1 ]
Poursadeghfard, Maryam [1 ]
Borhani-Haghighi, Afshin [1 ]
机构
[1] Shiraz Univ Med Sci, Clin Neurol Res Ctr, Shiraz, Iran
[2] Shahid Beheshti Univ Med Sci, Neurosci Res Ctr, Tehran, Iran
[3] Shiraz Univ Med Sci, Stem Cell Technol Res Ctr, Shiraz, Iran
[4] Univ Regensburg, Fac Biol & Preclin Med, Dept Behav & Mol Neurobiol, Regensburg, Germany
[5] Bushehr Univ Med Sci, Persian Gulf Marine Biotechnol Res Ctr, Bushehr, Iran
[6] Shiraz Univ Med Sci, Transplant Res Ctr, Shiraz, Iran
[7] Babol Univ Med Sci, Cellular & Mol Biol Res Ctr, Hlth Res Inst, Babol Sar, Iran
[8] Shiraz Univ Med Sci, Sch Med, Dept Physiol, Shiraz, Iran
基金
美国国家科学基金会;
关键词
bone marrow mesenchymal stem cells; cell therapy; cerebral ischemia; epidermal neural crest stem cells; Infarct volume; neurological deficits; MIDDLE CEREBRAL-ARTERY; REDUCES INFARCT SIZE; GENE-EXPRESSION; FUNCTIONAL RECOVERY; EPI-NCSC; OCCLUSION; MODEL; POPULATIONS; MOUSE; PCR;
D O I
10.1111/cns.13370
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Introduction Cell-based therapy is considered as promising strategy to cure stroke. However, employing appropriate type of stem cell to fulfill many therapeutic needs of cerebral ischemia is still challenging. In this regard, the current study was designed to elucidate therapeutic potential of epidermal neural crest stem cells (EPI-NCSCs) compared to bone marrow mesenchymal stem cells (BM-MSCs) in rat model of ischemic stroke. Methods Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) for 45 minutes. Immediately after reperfusion, EPI-NCSCs or BM-MSCs were transplanted via intra-arterial or intravenous route. A test for neurological function was performed before ischemia and 1, 3, and 7 days after MCAO. Also, infarct volume ratio and relative expression of 15 selected target genes were evaluated 7 days after transplantation. Results EPI-NCSCs transplantation (both intra-arterial and intravenous) and BM-MSCs transplantation (only intra-arterial) tended to result in a better functional outcome, compared to the MCAO group; however, this difference was not statistically significant. The infarct volume ratio significantly decreased in NCSC-intra-arterial, NCSC-intravenous and MSC-intra-arterial groups compared to the control. EPI-NCSCs interventions led to higher expression levels of Bdnf, nestin, Sox10, doublecortin, beta-III tubulin, Gfap, and interleukin-6, whereas neurotrophin-3 and interleukin-10 were decreased. On the other hand, BM-MSCs therapy resulted in upregulation of Gdnf, beta-III tubulin, and Gfap and down-regulation of neurotrophin-3, interleukin-1, and interleukin-10. Conclusion These findings highlight the therapeutic effects of EPI-NCSCs transplantation, probably through simultaneous induction of neuronal and glial formation, as well as Bdnf over-expression in a rat model of ischemic stroke.
引用
收藏
页码:670 / 681
页数:12
相关论文
共 59 条
[1]   Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia [J].
Argibay, Barbara ;
Trekker, Jesse ;
Himmelreich, Uwe ;
Beiras, Andres ;
Topete, Antonio ;
Taboada, Pablo ;
Perez-Mato, Maria ;
Vieites-Prado, Alba ;
Iglesias-Rey, Ramon ;
Rivas, Jose ;
Planas, Anna M. ;
Sobrino, Tomas ;
Castillo, Jose ;
Campos, Francisco .
SCIENTIFIC REPORTS, 2017, 7
[2]   Adult Stem Cell Therapy for Stroke: Challenges and Progress [J].
Bang, Oh Young ;
Kim, Eun Hee ;
Cha, Jae Min ;
Moon, Gyeong Joon .
JOURNAL OF STROKE, 2016, 18 (03) :256-266
[3]   Quantitative real-time RT-PCR analysis of inflammatory gene expression associated with ischemia-reperfusion brain injury [J].
Berti, R ;
Williams, AJ ;
Moffett, JR ;
Hale, SL ;
Velarde, LC ;
Elliott, PJ ;
Yao, CP ;
Dave, JR ;
Tortella, FC .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2002, 22 (09) :1068-1079
[4]   Optimizing the success of cell transplantation therapy for stroke [J].
Bliss, Tonya M. ;
Andres, Robert H. ;
Steinberg, Gary K. .
NEUROBIOLOGY OF DISEASE, 2010, 37 (02) :275-283
[5]  
Borhani-Haghighi A, 2013, IRAN J MED SCI, V38, P314
[6]   Neural crest stem cells from human epidermis of aged donors maintain their multipotency in vitro and in vivo [J].
Boroujeni, Samaneh Moghadasi ;
Koontz, Alison ;
Tseropoulos, Georgios ;
Kerosuo, Laura ;
Mehrotra, Pihu ;
Bajpai, Vivek K. ;
Selvam, Surya Rajan ;
Lei, Pedro ;
Bronner, Marianne E. ;
Andreadis, Stenos T. .
SCIENTIFIC REPORTS, 2019, 9 (1)
[7]   Why are MSCs therapeutic? New data: new insight [J].
Caplan, Al .
JOURNAL OF PATHOLOGY, 2009, 217 (02) :318-324
[8]   Human Epidermal Neural Crest Stem Cells (hEPI-NCSC)-Characterization and Directed Differentiation into Osteocytes and Melanocytes [J].
Clewes, Oliver ;
Narytnyk, Alla ;
Gillinder, Kevin R. ;
Loughney, Andrew D. ;
Murdoch, Alison P. ;
Sieber-Blum, Maya .
STEM CELL REVIEWS AND REPORTS, 2011, 7 (04) :799-814
[9]   Intraoperative Stem Cell Therapy [J].
Coelho, Monica Beato ;
Cabral, Joaquim M. S. ;
Karp, Jeffrey M. .
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 14, 2012, 14 :325-349
[10]   Doublecortin expression levels in adult brain reflect neurogenesis [J].
Couillard-Despres, S ;
Winner, B ;
Schaubeck, S ;
Aigner, R ;
Vroemen, M ;
Weidner, N ;
Bogdahn, U ;
Winkler, J ;
Kuhn, HG ;
Aigner, L .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2005, 21 (01) :1-14