scholarly journals Therapeutic Benefits by Human Mesenchymal Stem Cells (hMSCs) and Ang-1 Gene-Modified hMSCs after Cerebral Ischemia

2007 ◽  
Vol 28 (2) ◽  
pp. 329-340 ◽  
Author(s):  
Toshiyuki Onda ◽  
Osamu Honmou ◽  
Kuniaki Harada ◽  
Kiyohiro Houkin ◽  
Hirofumi Hamada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cerebral Artery ◽  
Human Mesenchymal Stem Cells ◽  
Artery Occlusion ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lesion Volume ◽  
Therapeutic Benefits ◽  
Cerebral Artery Occlusion

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.

scholarly journals Differential Migration of Mesenchymal Stem Cells to Ischemic Regions after Middle Cerebral Artery Occlusion in Rats

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0134920 ◽  
Author(s):  
Soo Hyun Lee ◽  
Kyung Sil Jin ◽  
Oh Young Bang ◽  
Byoung Joon Kim ◽  
Soo Jin Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Differential Migration ◽  
Cerebral Artery Occlusion

scholarly journals Effects of Magnetically Targeted Iron Oxide@Polydopamine-Labeled Human Umbilical Cord Mesenchymal Stem Cells In Cerebral Infarction In Mice

2021 ◽  
Author(s):  
Jun Yan ◽  
Te Liu ◽  
Jun Zhang ◽  
Bo Shi ◽  
Fuqiang Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Iron Oxide ◽  
Cerebral Infarction ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion ◽  
The Brain

Abstract Mesenchymal stem cells are a potential therapeutic candidate for cerebral infarction due to their anti-inflammatory proprieties. However, ensuring the engraftment of sufficient cells into the affected brain area remains a challenge. Herein, magnetic targeting techniques were used for the noninvasive transplantation of a large number of cells noninvasively. Mice subjected to permanent middle cerebral artery occlusion surgery were administered mesenchymal stem cells labeled or not with iron oxide@polydopamine nanoparticles by tail vein injection. Iron oxide@polydopamine particles were characterized by transmission electron microscopy, and labeled mesenchymal stem cells were characterized by flow cytometry and their differentiation potential was assessed in vitro . Following the systemic injection of iron oxide@polydopamine-labeled mesenchymal stem cells into permanent transient middle cerebral artery occlusion-induced mice, magnetic navigation increased the MSCs localization to the brain lesion site and reduced the lesion volume. Treatment with iron oxide@polydopamine-labeled mesenchymal stem cells also significantly inhibited M1 microglia polarization and increased M2 microglia cell infiltration. Furthermore, western blotting and immunohistochemical analysis demonstrated that microtubule-associated protein 2 and NeuN levels were upregulated the brain tissue of mice treated with iron oxide@polydopamine-labeled mesenchymal stem cells. Thus, iron oxide@polydopamine-labeled mesenchymal stem cells attenuated brain injury and protected neurons by preventing pro-inflammatory microglia activation. Overall, the proposed iron oxide@polydopamine-labeled mesenchymal stem cells approach may overcome the major drawback of the conventional MSCs therapy for the treatment of cerebral infarction.

scholarly journals Intravenously Delivered Allogeneic Mesenchymal Stem Cells Bidirectionally Regulate Inflammation and Induce Neurotrophic Effects in Distal Middle Cerebral Artery Occlusion Rats Within the First 7 Days After Stroke

2018 ◽  
Vol 46 (5) ◽  
pp. 1951-1970 ◽  
Author(s):  
XiaoBo Li ◽  
Min Huang ◽  
RenChao Zhao ◽  
ChunSong Zhao ◽  
Yao Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Ischemic Core ◽  
Cerebral Artery Occlusion ◽  
Distal Middle Cerebral Artery

Background/Aims: Neurotrophic effects and immunosuppression are the main therapeutic mechanisms of mesenchymal stem cells (MSCs) in stroke treatment. Neurotrophins are produced by graft cells, host neurons, astrocytes, and even microglia/macrophages. Meanwhile, MSCs can increase inflammation if they are not sufficiently induced by pro-inflammatory cytokines. We examined whether intravenously transplanted bone marrow MSCs (BM-MSCs) increase inflammation in distal middle cerebral artery occlusion (dMCAO) rats, how long the increased inflammation effect persists for, and what the final therapeutic outcomes will be. We also tested the neurotrophic role of BM-MSCs and attempted to identify the neurotrophin-producing cells. Methods: At 1 h after dMCAO was performed on Sprague-Dawley rats, allogeneic BM-MSCs were transplanted intravenously. The infarct volume was examined by Tetrazolium Red staining at 2 days (day 2), and the behavioral tests (cylinder test and grid walking test) were performed at 2, 4 (day 4) and 7 days (day 7) after transplantation. The concentrations of inflammation related cytokines and neurotrophins in the ischemic cortex, ipsilateral striatum, and serum, were measured using ELISA at days 2-7. The cell source of neurotrophins was observed by immunohistochemistry. Results: The transplanted cells were mainly found in the infarct border zone (IBZ) of the brain. Infarct volume was reduced and behavioral outcomes were improved at 2 days after ischemia. In the striatum and circulation, BM-MSC transplantation increased inflammation at day 2 and decreased it at day 7. At days 2-7, insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) concentrations in the ischemic core of the cortex were significantly higher in the BM-MSC group than in the ischemia vehicle group. IGF-1 and BDNF were derived mainly from host microglia/macrophages in the ischemic core, and transplanted cells in the IBZ. At day 2, BM-MSC transplantation significantly increased the number of IGF-1+CD68+ and BDNF+Iba-1+ double positive cells in the ischemic core cortex. Conclusions: Although increased inflammation, BM-MSCs were still beneficial to dMCAO recovery at day 2. The immunopromoting effect of MSCs was transient and shifted to an immunosuppressive action at day 7. The neurotrophic factors IGF-1 and BDNF, which were mainly derived from transplanted BM-MSCs and host microglia/macrophages, contributed to the therapeutic effects from day 2 to day 7.

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