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Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats.

Leu S, Lin YC, Yuen CM, Yen CH, Kao YH, Sun CK, Yip HK - J Transl Med (2010)

Bottom Line: The results showed that BIA was larger in control group than in treatment group (p < 0.001).Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

ABSTRACT

Background: The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated.

Methods: Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 x 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure.

Results: The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).

Conclusions: ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.

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Related in: MedlinePlus

The number of GFAP-positive cells in brain infarct area. IHC staining (D) (200×) showing significantly higher number of glial fibrillary acid protein (GFAP)-positive cells (red arrows) in group 2 (B) than in groups 1 (A) and 3 (C), and no difference between groups 1 and 3. n = 10 per group. Scale bars in right lower corner represent 50 μm. * vs. †, p < 0.0001.
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Figure 10: The number of GFAP-positive cells in brain infarct area. IHC staining (D) (200×) showing significantly higher number of glial fibrillary acid protein (GFAP)-positive cells (red arrows) in group 2 (B) than in groups 1 (A) and 3 (C), and no difference between groups 1 and 3. n = 10 per group. Scale bars in right lower corner represent 50 μm. * vs. †, p < 0.0001.

Mentions: The expression of doublecortin, an indication of migrating neuroblasts, was remarkably upregulated in group 3 compared with group 2 (Figure 7A-D). Additionally, IHC staining showed that the expression of vWF, a marker of endothelial cells of cerebral blood vessels, was significantly increased in group 3 than in group 2 (Figure 7E-H). Moreover, IHC staining also revealed a notably increased number of BrdU-positive cells (Figure 8A-D) in group 3 than in group 2, implying an increased cellular differentiation and proliferation after ADMSC treatment. Furthermore, the number of arterioles (≤ 15 μm in diameter) in BIA was substantially lower in group 2 than in groups 1 and 3 on IHC staining (Figure 9A-D). All of these findings indicate an ADMSC-induced enhancement in neurogenesis and vasculogenesis after acute IS.


Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats.

Leu S, Lin YC, Yuen CM, Yen CH, Kao YH, Sun CK, Yip HK - J Transl Med (2010)

The number of GFAP-positive cells in brain infarct area. IHC staining (D) (200×) showing significantly higher number of glial fibrillary acid protein (GFAP)-positive cells (red arrows) in group 2 (B) than in groups 1 (A) and 3 (C), and no difference between groups 1 and 3. n = 10 per group. Scale bars in right lower corner represent 50 μm. * vs. †, p < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2913939&req=5

Figure 10: The number of GFAP-positive cells in brain infarct area. IHC staining (D) (200×) showing significantly higher number of glial fibrillary acid protein (GFAP)-positive cells (red arrows) in group 2 (B) than in groups 1 (A) and 3 (C), and no difference between groups 1 and 3. n = 10 per group. Scale bars in right lower corner represent 50 μm. * vs. †, p < 0.0001.
Mentions: The expression of doublecortin, an indication of migrating neuroblasts, was remarkably upregulated in group 3 compared with group 2 (Figure 7A-D). Additionally, IHC staining showed that the expression of vWF, a marker of endothelial cells of cerebral blood vessels, was significantly increased in group 3 than in group 2 (Figure 7E-H). Moreover, IHC staining also revealed a notably increased number of BrdU-positive cells (Figure 8A-D) in group 3 than in group 2, implying an increased cellular differentiation and proliferation after ADMSC treatment. Furthermore, the number of arterioles (≤ 15 μm in diameter) in BIA was substantially lower in group 2 than in groups 1 and 3 on IHC staining (Figure 9A-D). All of these findings indicate an ADMSC-induced enhancement in neurogenesis and vasculogenesis after acute IS.

Bottom Line: The results showed that BIA was larger in control group than in treatment group (p < 0.001).Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

ABSTRACT

Background: The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated.

Methods: Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 x 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure.

Results: The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).

Conclusions: ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.

Show MeSH
Related in: MedlinePlus