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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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mRNA expressions of apoptosis-related genes and number of apoptotic cells in brain infarct area. (A) Bcl-2 mRNA expression was significantly higher in groups 1 and 3 than in group 2 and notably higher in group 1 than in group 3. (B) Bax mRNA expression was notably higher in group 2 than in groups 1 and 3 and significantly higher in group 3 than in group 1. (C) Caspase 3 mRNA significantly higher in groups 2 and 3 than in group 1, but it did not differ between group 2 and group 3. (D) IL-8/Gro mRNA expression was remarkably higher in groups 2 and 3 than in group 1 and notably higher in group 3 than in group 2. * vs. †, p < 0.05; * vs. ‡, p < 0.05; † vs. ‡, p < 0.05. The number of apoptotic nuclei (H)) (400×) significantly higher in group 2 (F) than in groups 1 (G) and 3 (E), and notably higher in group 3 than in group 1. (n = 10 per group) * vs. † vs. ‡, p < 0.001. Scale bar in right lower corner represent 20 μm.
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Figure 4: mRNA expressions of apoptosis-related genes and number of apoptotic cells in brain infarct area. (A) Bcl-2 mRNA expression was significantly higher in groups 1 and 3 than in group 2 and notably higher in group 1 than in group 3. (B) Bax mRNA expression was notably higher in group 2 than in groups 1 and 3 and significantly higher in group 3 than in group 1. (C) Caspase 3 mRNA significantly higher in groups 2 and 3 than in group 1, but it did not differ between group 2 and group 3. (D) IL-8/Gro mRNA expression was remarkably higher in groups 2 and 3 than in group 1 and notably higher in group 3 than in group 2. * vs. †, p < 0.05; * vs. ‡, p < 0.05; † vs. ‡, p < 0.05. The number of apoptotic nuclei (H)) (400×) significantly higher in group 2 (F) than in groups 1 (G) and 3 (E), and notably higher in group 3 than in group 1. (n = 10 per group) * vs. † vs. ‡, p < 0.001. Scale bar in right lower corner represent 20 μm.

Mentions: By day 21 following ADMSCs implantation, immunofluorescence stain (Figure 2E-F) identified that numerous CM-Dil-stained ADMSCs were found to be present in infarct area. This finding indicates that ADMSCs was able to migrate (i.e. homing) to brain infarcted area after venous injection.


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)

mRNA expressions of apoptosis-related genes and number of apoptotic cells in brain infarct area. (A) Bcl-2 mRNA expression was significantly higher in groups 1 and 3 than in group 2 and notably higher in group 1 than in group 3. (B) Bax mRNA expression was notably higher in group 2 than in groups 1 and 3 and significantly higher in group 3 than in group 1. (C) Caspase 3 mRNA significantly higher in groups 2 and 3 than in group 1, but it did not differ between group 2 and group 3. (D) IL-8/Gro mRNA expression was remarkably higher in groups 2 and 3 than in group 1 and notably higher in group 3 than in group 2. * vs. †, p < 0.05; * vs. ‡, p < 0.05; † vs. ‡, p < 0.05. The number of apoptotic nuclei (H)) (400×) significantly higher in group 2 (F) than in groups 1 (G) and 3 (E), and notably higher in group 3 than in group 1. (n = 10 per group) * vs. † vs. ‡, p < 0.001. Scale bar in right lower corner represent 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: mRNA expressions of apoptosis-related genes and number of apoptotic cells in brain infarct area. (A) Bcl-2 mRNA expression was significantly higher in groups 1 and 3 than in group 2 and notably higher in group 1 than in group 3. (B) Bax mRNA expression was notably higher in group 2 than in groups 1 and 3 and significantly higher in group 3 than in group 1. (C) Caspase 3 mRNA significantly higher in groups 2 and 3 than in group 1, but it did not differ between group 2 and group 3. (D) IL-8/Gro mRNA expression was remarkably higher in groups 2 and 3 than in group 1 and notably higher in group 3 than in group 2. * vs. †, p < 0.05; * vs. ‡, p < 0.05; † vs. ‡, p < 0.05. The number of apoptotic nuclei (H)) (400×) significantly higher in group 2 (F) than in groups 1 (G) and 3 (E), and notably higher in group 3 than in group 1. (n = 10 per group) * vs. † vs. ‡, p < 0.001. Scale bar in right lower corner represent 20 μm.
Mentions: By day 21 following ADMSCs implantation, immunofluorescence stain (Figure 2E-F) identified that numerous CM-Dil-stained ADMSCs were found to be present in infarct area. This finding indicates that ADMSCs was able to migrate (i.e. homing) to brain infarcted area after venous injection.

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