Early Protective Effect of Bone Marrow Mononuclear Cells Against Ischemic White Matter Damage Through Augmentation of Cerebral Blood Flow

Purpose: To evaluate the efficacy of autologous transplantation of granulocyte colony-stimulating factor (G-CSF) stimulated bone marrow mononuclear cells in the treatment of diabetic lower limb ischemic disease in a rabbit model. Methods: The diabetic model was produced by intravenous injection of 5% alloxan into New Zealand white rabbits. The lower limb ischemia model was created by femoral artery ligation in diabetic rabbits (n=50) 14 days after alloxan injection. Animals were then randomized into five groups (10 rabbits per group): group 1, transplanted with G-CSF immobilized peripheral blood mononuclear cells (PBMNC); group 2, transplanted with G-CSF stimulated bone marrow mononuclear cells (BMMNC); group 3, animals were transplanted with non-stimulated BMMNCs; group 4, G-CSF group injected with G-CSF alone without transplantation; and group 5, PBS group treated with PBS alone. Necrosis of foot or toes and blood flow recovery in ischemic limbs was assessed. Expression of von Willebrand factor (vWF) and vascular endothelial cell growth factor (VEGF) were measured in ischemic muscles by immunohistochemistry analysis. Results: Blood flow in ischemic limbs was significantly improved in the G-BMMNC group (ratio of blood flows: 0.82±0.06) in comparison with the G-PBMNC (0.61±0.09) and BMMNC (0.62±0.08) groups (P < 0.001). In the G-BMMNC group, the capillary density, a measure of vWF expression, was significantly higher than in either the G-PBMNC or BMMNC groups (47.9±2.51 vs. 36.8±4.16 and 39.6±2.72, respectively, P < 0.05). The expression of VEGF in G-BMMNC animals was significantly increased in comparison with the G-PBMNC and BMMNC groups (16.93±0.70 vs. 11.83±0.98 and 12.32±0.96, respectively, P < 0.05). Conclusion: A combination of G-CSF stimulation and autologous transplantation of bone marrow stem cells synergistically improved neovascularization and angiogenesis in ischemic limb tissues in diabetic rabbits.

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Impaired potency of bone marrow mononuclear cells for inducing therapeutic angiogenesis in obese diabetic rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00766.2005 ◽

2006 ◽

Vol 290 (4) ◽

pp. H1362-H1369 ◽

Cited By ~ 31

Author(s):

Tao-Sheng Li ◽

Akira Furutani ◽

Masaya Takahashi ◽

Mako Ohshima ◽

Shu-Lan Qin ◽

...

Keyword(s):

Bone Marrow ◽

Blood Flow ◽

Receptor Antagonist ◽

Mononuclear Cells ◽

Limb Ischemia ◽

Therapeutic Angiogenesis ◽

Diabetic Rats ◽

Bone Marrow Mononuclear Cells ◽

Obese Diabetic Rats ◽

Cell Colony

Using Zucker fatty rats, a strain characterized by diabetes and hyperlipidemia, we investigated the diabetes- and hyperlipidemia-related impairment of bone marrow mononuclear cells (BMCs) for inducing therapeutic angiogenesis. BMCs from Zucker fatty and normal Zucker lean rats were collected and cultured. Although the characterization and cell survival of BMCs did not differ, the VEGF production, endothelial differentiation, and endothelial cell colony-forming potential of BMCs from Zucker fatty rats were significantly lower than those of BMCs from lean rats. By using an ischemic hindlimb model, we found that the native recovery of induced limb ischemia in the Zucker fatty rats was also significantly worse than that in the lean rats. Furthermore, the expression of 5-hydroxytryptamine (5-HT2A) receptors was obviously higher in the Zucker fatty rats than that in the lean rats and was enhanced after limb ischemia. Although the therapeutic potency was lower than with the implantation of BMCs from normal lean rats, the implantation of BMCs from fatty rats could also induce angiogenesis and increase blood flow significantly in the ischemic hindlimbs of Zucker fatty rats. Furthermore, the blood flow in the ischemic hindlimbs was increased by the administration of sarpogrelate, a selective 5-HT2A-receptor antagonist. Our results clearly show diabetes- and hyperlipidemia-related dysfunction and impaired potency for inducing angiogenesis of BMCs. However, the implantation of autologous BMCs into ischemic limbs of diabetic and hyperlipidemic rats has induced therapeutic angiogenesis effectively, and blood flow would be enhanced by the administration of a 5-HT2A-receptor antagonist.

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Correlation Analysis Between Local Cerebral Blood Flow and Severity of Vascular Cognitive Dysfunction

Journal of Medical Imaging and Health Informatics ◽

10.1166/jmihi.2021.3529 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1798-1806

Author(s):

Jinling Wang ◽

Xin Xu ◽

Wanhui Dong

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

White Matter ◽

Cognitive Dysfunction ◽

Control Group ◽

Disease Group ◽

White Matter Damage ◽

Brain White Matter ◽

Flow Perfusion ◽

Cerebrovascular Stenosis

Research methods: This paper analyses the correlation between cerebral blood flow perfusion caused by cerebral vascular stenosis and the reduction of patients with cognitive dysfunction and white matter damage. A total of 118 patients with reduced cerebral blood flow perfusion due to cerebrovascular stenosis were selected to be included in the disease group, and 118 patients with no cerebrovascular stenosis and no neurological disease were included in the control group. The cerebral blood flow perfusion index and cognitive function index were compared between the two groups of patients. The correlation between each index and the degree of brain white matter damage was analysed. Results: The scores of brain white matter damage in patients with disease group were higher than those in control group, and cCBV, cCBF, TTP, MTT, MoCA, MMSE, ADL, and WMS were lower than those in control group, and the difference was statistically significant (P < 0.05). cCBV, cCBF, TTP, MTT, and white matter damage scores were highly correlated with MoCA, MMSE, ADL, and WMS (P < 0.05). There is a clear correlation between cerebral vascular perfusion, cognitive dysfunction, and white matter damage in patients with cerebrovascular stenosis. The more severe the perfusion of cerebral blood flow, the more severe the cognitive dysfunction and the white matter damage.

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