Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

Autor: Haoliang Xue, Shuo Wu, Yiduo Zhou, Baixin Shen, Jie Gao, Liucheng Ding, Yi Huang, Yunpeng Shao, Zhongqing Wei
Jazyk: angličtina
Rok vydání: 2020
Předmět:
CD31
Male
Vascular Endothelial Growth Factor A
Angiogenesis
Basic fibroblast growth factor
Proliferation
Medicine (miscellaneous)
Bone Marrow Cells
Protein Serine-Threonine Kinases
Mesenchymal Stem Cell Transplantation
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Bone marrow-derived mesenchymal stem cells
Streptozocin
Diabetes Mellitus
Experimental
Andrology
Rats
Sprague-Dawley
lcsh:Biochemistry
chemistry.chemical_compound
Bone Marrow
Antiapoptosis
Medicine
Animals
Humans
lcsh:QD415-436
Integrin-linked kinase
lcsh:R5-920
Glycogen Synthase Kinase 3 beta
business.industry
Research
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Streptozotocin
Rats
Vascular endothelial growth factor
Endothelial stem cell
medicine.anatomical_structure
chemistry
Molecular Medicine
Bone marrow
Diabetic cystopathy
business
lcsh:Medicine (General)
medicine.drug
Zdroj: Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-15 (2020)
Stem Cell Research & Therapy
ISSN: 1757-6512
Popis: Background Diabetic cystopathy (DCP) is a chronic complication of diabetes mainly within the submucosal and muscular layers of the bladder due to the hyperglycemia-induced ischemia. As no effective therapies are currently available, the administration of optimized mesenchymal stem cells (MSCs) provides a potential treatment of DCP. Thus far, new strategy, such as genetic modification of MSCs, has been developed and has shown promising outcomes of various disorders. Methods This study was conducted using integrin-linked kinase (ILK) gene-modified bone marrow-derived stem cells (BMSCs) for streptozotocin (STZ)-induced diabetic cystopathy in a rat model. In total, 68 male Sprague-Dawley rats were randomized into five groups: sham control (control group, n = 10); DCP model alone (DM group, n = 10); DCP rats intravenously treated with BMSCs (BMSC group, n = 16); DCP rats accepted adenoviral vector-infected BMSCs (Ad-null-BMSC group, n = 16) and DCP rats accepted ILK adenoviral vector-infected BMSCs (Ad-ILK-BMSC group, n = 16). Diabetic rats accepted cell transplantation in the experimental group (2 rats per group) were sacrificed for the bladder tissue on the third day, 7th day, and 14th day of treatment respectively ahead of schedule. At 4 weeks after treatment, all rats in five groups accepted urodynamic studies to evaluate bladder function and were sacrificed for bladder tissue. Results Our data showed that the underactive bladder function was significantly improved in DCP rats intravenously treated with ILK gene-modified BMSCs compared to those in the DM, BMSCs, and Ad-null-BMSC group. Meanwhile, we found that gene-modified BMSC treatment significantly promoted the activation of the AKT/GSK-3β pathway by increasing phosphorylation and led to the enhancement of survival. In addition, the expression levels of angiogenesis-related protein vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1 (SDF-1) were significantly higher in the Ad-ILK-BMSC group than that in the DM, BMSCs, and Ad-null-BMSC group as assessed by enzyme-linked immunosorbent assay and western blot. As two indicators of vascular endothelial cell markers, the expression of von Willebrand factor (vWF) and CD31 by western blot and immunofluorescent staining revealed that the percentage of the vascular area of the bladder tissue significantly increased in Ad-ILK-BMSC group compared with the BMSCs and Ad-null-BMSC group on the 14th day of treatment. Histological and immunohistochemical staining (hematoxylin and eosin (HE), vWF, Ki67, and TUNNEL) on the bladder tissue revealed statistically different results between groups. Conclusion ILK gene-modified BMSCs restored the bladder function and histological construction via promoting the process of angiogenesis and protecting cells from high glucose-associated apoptosis in STZ-induced DCP rat model, which provides a potential for the treatment of patients with DCP.
Databáze: OpenAIRE
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