Integrin-Linked Kinase Improves Functional Recovery of Diabetic Cystopathy and Mesenchymal Stem Cell Survival and Engraftment in Rats

Huang, Yi; Ding, Liang; Shao, Yunpeng; Chen, Zhengsen; Shen, Baixin; Ma, Yinchao; Zhu, Ling; Wei, Zuoan

doi:10.1016/j.jcjd.2016.11.002

Cited by 4 publications

(7 citation statements)

References 33 publications

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“…BMSCs from passages 3-5 were used in all experiments. Meanwhile, the identification of BMSCs was performed as described by our previous study [27], such as cell surface markers, Oil-Red-O staining, and von Kossa staining.…”

Section: Isolation and Culture Of Bmscsmentioning

confidence: 99%

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

et al. 2020

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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

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Section: Isolation and Culture Of Bmscsmentioning

confidence: 99%

“…A diabetic rat model was performed using streptozotocin (STZ) described by our previous study [27]. Briefly, SD male rats (76 in total, age 10-12 weeks) were fasted for 16 h before diabetes induction.…”

Section: Preparation Of Diabetic Rat Modelmentioning

confidence: 99%

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

et al. 2020

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“…Urodynamic studies were performed as described previously 5 days after treatment . Contractile responses of rat detrusor smooth muscle were measured according to the procedure by KE Atalik …”

Section: Methodsmentioning

confidence: 99%

Curcumin ameliorates cisplatin‐induced cystopathy via activating NRF2 pathway

Shao

Zhou

et al. 2018

Neurourology and Urodynamics

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“…Osteopontin‐positive cells ameliorate diabetes‐induced long‐term HSC dysfunction . Integrin‐linked kinase overexpression improves diabetic cystopathy, characterized by peripheral neuropathy–associated bladder dysfunction . BM cells secrete multiple angiogenic and neurotrophic cytokines and are used to treat diabetic neuropathy.…”

Section: Bm Stem Cells Ameliorate Neuropathy Via Angiogenic and Neuromentioning

confidence: 99%

“…41 Integrin-linked kinase overexpression improves diabetic cystopathy, characterized by peripheral neuropathy-associated bladder dysfunction. 75 BM cells secrete multiple angiogenic and neurotrophic cytokines and are used to treat diabetic neuropathy. In particular, EPCs trigger profitable therapeutic effects via improved neural neovascularization and neuroprotective effects.…”

Section: Albiero Et Al 9 2014mentioning

confidence: 99%

Neuropathy and inflammation in diabetic bone marrow

Zhou

Zuo

Qian

2018

Diabetes Metabolism Res

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Summary Diabetes impairs the bone marrow (BM) architecture and function as well as the mobilization of immature cells into the bloodstream and number of potential regenerative cells. Circadian regulation of bone immature cell migration is regulated by β‐adrenergic receptors, which are expressed on haematopoietic stem cells, mesenchymal stem cells, and osteoblasts in the BM. Diabetes is associated with a substantially lower number of sympathetic nerve terminal endings in the BM; thus, diabetic neuropathy plays a critical role in BM dysfunction. Treatment with mesenchymal stem cells, BM mononuclear cells, haematopoietic stem cells, and stromal cells ameliorates the dysfunction of diabetic neuropathy, which occurs, in part, through secreted neurotrophic factors, growth factors, adipokines, and polarizing macrophage M2 cells and inhibiting inflammation. Inflammation may be a therapeutic target for BM stem cells to improve diabetic neuropathy. Given that angiogenic and neurotrophic effects are two major barriers to effective diabetic neuropathy therapy, targeting BM stem cells may provide a novel approach to develop these types of treatments.

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Integrin-Linked Kinase Improves Functional Recovery of Diabetic Cystopathy and Mesenchymal Stem Cell Survival and Engraftment in Rats

Cited by 4 publications

References 33 publications

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

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

Curcumin ameliorates cisplatin‐induced cystopathy via activating NRF2 pathway

Neuropathy and inflammation in diabetic bone marrow

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