Intravenous Administration of Hair Follicle Mesenchymal Stem Cells and Insulin Growth Factor-1 Improves the Neurological Performances of Rats Following Focal Cerebral Ischemia

Author(s):  
Xuemei Zhang ◽  
li wei ◽  
Yinglian Zhou ◽  
Yuanjiao Ouyang ◽  
Duo Wang ◽  
...  

Abstract Background: Focal cerebral ischemia is a common cerebrovascular disease with limited treatment options, and new treatments are therefore urgently needed. Hair follicle mesenchymal stem cells (HF-MSCs) are considered ideal cells for the treatment of neurological disorders. Insulin growth factor-1 (IGF-1) is an effective neuroprotective compound. Methods: In the present study, we used middle cerebral artery occlusion (MCAO) model to evaluate the therapeutic effects of HF-MSCs and IGF-1 in focal cerebral ischemia. After middle cerebral artery occlusion (MCAO), rats were randomly divided into six groups. HF-MSCs and IGF-1 were transplanted into rat models by tail vein injection. The fate of transplanted HF-MSCs in the rat brain was assessed using immunofluorescence, immunohistochemistry, Western blot analysis, and reverse transcription polymerase chain reaction (RT-PCR). Beam balance tests and neurological severity scores were used to assess neurological recovery. Results: HF-MSCs labeled with the green fluorescent dye PKH67 were found to colocalize with 4',6-diamidino-2-phenylindole (DAPI) and neural-specific markers. Rats in the HF-MSCs, IGF-1 and HF-MSCs + IGF-1 groups exhibited neural differentiation marker expression, with those in the HF-MSCs + IGF-1 group exhibiting the highest levels. Conclusions: These results suggest that the combined treatment of HF-MSCs and IGF-1 can enhance neurological recovery, representing a new therapeutic strategy for cerebral ischemia.

2009 ◽  
Vol 29 (4) ◽  
pp. 780-791 ◽  
Author(s):  
Yi-Ping Liu ◽  
Hakan Seçkin ◽  
Yusuf İzci ◽  
Zhong Wei Du ◽  
Yi-Ping Yan ◽  
...  

Embryonic mesenchymal stem cells (eMSCs) were first derived from human embryonic stem cells (hESCs) overexpressing green fluorescence protein (GFP). They expressed CD29, CD44, CD73, CD105, CD166 and nestin, but not CD34, CD45, CD106 SSEA-4 or Oct3/4. Twenty million eMSCs in 1mL of phosphate-buffered saline (PBS) were injected into the femoral veins of spontaneously hypertensive rats after transient middle cerebral artery occlusion. The migration and differentiation of the eMSCs in the ischemic brain were analyzed. The results revealed that eMSCs migrated to the infarction region and differentiated into neurons, which were positive for β-tubulin III, microtubule-associated protein 2 (MAP2), HuC, neurofilament and human nuclear antibody, and to vascular endothelial cells, which were positive for von Willebrand factor (vWF). The transplanted cells survived in the infarction region for at least 4 weeks. Adhesive removal function significantly improved in the first week after cell transplantation, and rotarod motor function significantly improved starting from the second week. The infarction volume in the eMSC group was significantly smaller than that in the PBS control group at 4 weeks after infusion. The results of this study show that when administered intravenously, eMSCs differentiated into neuronal and endothelial cells, reduced the infarction volume, and improved behavioral functional outcome significantly in transient focal cerebral ischemia.


2007 ◽  
Vol 28 (2) ◽  
pp. 329-340 ◽  
Author(s):  
Toshiyuki Onda ◽  
Osamu Honmou ◽  
Kuniaki Harada ◽  
Kiyohiro Houkin ◽  
Hirofumi Hamada ◽  
...  

Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC- and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome.


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