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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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Proposed mechanisms underlying therapeutic effects of SDMCs on reducing brain infarct area and improving neurological function.
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Figure 12: Proposed mechanisms underlying therapeutic effects of SDMCs on reducing brain infarct area and improving neurological function.

Mentions: The present study has limitations. First, although the mechanisms underlying the therapeutic potential of ADMSC in attenuating BIA and enhancing sensorimotor functional recovery have been carefully elucidated, the precise mechanistic basis of ADMSC treatment for acute IS may be more complex. The proposed mechanisms of potential impacts of ADMSC implantation on improving sensorimotor dysfunction in the rat have been summarized in Figure 12. Second, although the short-term outcome was impressive, this current study does not provide the information for how long the therapeutic effect will be maintained.


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)

Proposed mechanisms underlying therapeutic effects of SDMCs on reducing brain infarct area and improving neurological function.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 12: Proposed mechanisms underlying therapeutic effects of SDMCs on reducing brain infarct area and improving neurological function.
Mentions: The present study has limitations. First, although the mechanisms underlying the therapeutic potential of ADMSC in attenuating BIA and enhancing sensorimotor functional recovery have been carefully elucidated, the precise mechanistic basis of ADMSC treatment for acute IS may be more complex. The proposed mechanisms of potential impacts of ADMSC implantation on improving sensorimotor dysfunction in the rat have been summarized in Figure 12. Second, although the short-term outcome was impressive, this current study does not provide the information for how long the therapeutic effect will be maintained.

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