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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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Comparison of infarct area and sensorimotor function in rats with and without ADMSC treatment. (A & B) Identification of gross infarct area (blue arrows) with and without ADMSC treatment, respectively. (C) Significantly lower ratio of infarct area to total coronal section area in stroke + ADMSC group (group 3) compared with stroke group (group 2) (n = 5 per group). † vs. *, p < 0.001. (D) The results of Corner test on days 0, 3, 7, 14, and 21 after acute IS, showing a steady state of neurological functional impairment on day 3 following acute IS in both group 2 and group 3. Significant improvement in neurological function noted only in group 3 compared with group 2 on day 14 and substantially improved on day 21 after acute IS. Significance of difference at respective time point: * p < 0.005, group 2 vs. group 3; † p < 0.002, group 2 vs. group 3. (E) and (F) Identification of CM-DiI-stained ADMSCs (yellow arrows) in brain infarct area of two rats from group 3. Scale bars in right lower corner represent 50 μm.
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Figure 2: Comparison of infarct area and sensorimotor function in rats with and without ADMSC treatment. (A & B) Identification of gross infarct area (blue arrows) with and without ADMSC treatment, respectively. (C) Significantly lower ratio of infarct area to total coronal section area in stroke + ADMSC group (group 3) compared with stroke group (group 2) (n = 5 per group). † vs. *, p < 0.001. (D) The results of Corner test on days 0, 3, 7, 14, and 21 after acute IS, showing a steady state of neurological functional impairment on day 3 following acute IS in both group 2 and group 3. Significant improvement in neurological function noted only in group 3 compared with group 2 on day 14 and substantially improved on day 21 after acute IS. Significance of difference at respective time point: * p < 0.005, group 2 vs. group 3; † p < 0.002, group 2 vs. group 3. (E) and (F) Identification of CM-DiI-stained ADMSCs (yellow arrows) in brain infarct area of two rats from group 3. Scale bars in right lower corner represent 50 μm.

Mentions: Data were expressed as mean values (mean ± SD). The significance of differences between two groups was evaluated with t-test. The significance of differences among three groups was evaluated using analysis of variance followed by Bonferroni multiple-comparison post hoc test. Statistical analyses were performed using SAS statistical software for Windows version 8.2 (SAS institute, Cary, NC). A probability value < 0.05 was considered statistically significant.


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)

Comparison of infarct area and sensorimotor function in rats with and without ADMSC treatment. (A & B) Identification of gross infarct area (blue arrows) with and without ADMSC treatment, respectively. (C) Significantly lower ratio of infarct area to total coronal section area in stroke + ADMSC group (group 3) compared with stroke group (group 2) (n = 5 per group). † vs. *, p < 0.001. (D) The results of Corner test on days 0, 3, 7, 14, and 21 after acute IS, showing a steady state of neurological functional impairment on day 3 following acute IS in both group 2 and group 3. Significant improvement in neurological function noted only in group 3 compared with group 2 on day 14 and substantially improved on day 21 after acute IS. Significance of difference at respective time point: * p < 0.005, group 2 vs. group 3; † p < 0.002, group 2 vs. group 3. (E) and (F) Identification of CM-DiI-stained ADMSCs (yellow arrows) in brain infarct area of two rats from group 3. Scale bars in right lower corner represent 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Comparison of infarct area and sensorimotor function in rats with and without ADMSC treatment. (A & B) Identification of gross infarct area (blue arrows) with and without ADMSC treatment, respectively. (C) Significantly lower ratio of infarct area to total coronal section area in stroke + ADMSC group (group 3) compared with stroke group (group 2) (n = 5 per group). † vs. *, p < 0.001. (D) The results of Corner test on days 0, 3, 7, 14, and 21 after acute IS, showing a steady state of neurological functional impairment on day 3 following acute IS in both group 2 and group 3. Significant improvement in neurological function noted only in group 3 compared with group 2 on day 14 and substantially improved on day 21 after acute IS. Significance of difference at respective time point: * p < 0.005, group 2 vs. group 3; † p < 0.002, group 2 vs. group 3. (E) and (F) Identification of CM-DiI-stained ADMSCs (yellow arrows) in brain infarct area of two rats from group 3. Scale bars in right lower corner represent 50 μm.
Mentions: Data were expressed as mean values (mean ± SD). The significance of differences between two groups was evaluated with t-test. The significance of differences among three groups was evaluated using analysis of variance followed by Bonferroni multiple-comparison post hoc test. Statistical analyses were performed using SAS statistical software for Windows version 8.2 (SAS institute, Cary, NC). A probability value < 0.05 was considered statistically significant.

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