Angiogenesis in diabetic mouse model with critical limb ischemia; cell and gene therapy

Asadi-Yousefabad, Seyedeh-Leili; Nammian, Pegah; Tabei, Seyed Mohammad Bagher; Daneshi, Sajad; Fallahi, Jafar; Razban, Vahid; Sheikhha, Mohammad Hasan

doi:10.1016/j.mvr.2022.104339

Cited by 8 publications

(8 citation statements)

References 52 publications

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“…Our result showed that diabetic rat treated with S-MSCs improved functional behavior faster in comparison with PAD group. In line with our finding, previous study showed that transplantation of MSCsmiR-126 recovered hind limb blood flow and showed the effect of proangiogenic cytokines in diabetic mice ( 23 ). Another study revealed that the use of BM-MSC type stem cells promote better functional results in the treatment group than the control group with the fastest increase in the Tarlov score on days 14, 21, and 28 ( 25 ).…”

Section: Discussionsupporting

confidence: 92%

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Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease

Sazli¹,

Lindarto²,

Hasan³

et al. 2023

Med Arch

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Background: Lower limb peripheral artery disease (PAD) is the main risk of diabetes mellitus which result to high mortality rate. Approximately, 50% of patients who receive several treatments have passed away or lost limbs at a year’s follow-up. Secretome of hypoxia mesenchymal stem cells (S-MSCs) contains several active soluble molecules from hypoxia MSCs (H-MSCs) that capable inducing anti-inflammatory and vascular regeneration in PAD. Objective: In this study, we investigated the therapeutic potential of S-MSCs in improving dynamic function and angiogenesis of PAD diabetic rats. Methods: The PAD was established by the incision from the groin to the inner thigh and distal ligation of femoral arteries in rats with diabetes. Rats were administered with 200 µL and 400 µL S-MSCs that successfully filtrated using tangential flow filtration (TFF) system based on various molecular weight cut-off categories intravenously. ELISA assay was used to analyze the cytokines and growth factors contained in S-MSCs. Tarlov score were examined at day 1, 3, 5, 7, 10 and 14. The rats were sacrificed at day 14 and muscle tissues were collected for immunohistochemistry (IHC) and gene expression analysis. Results: ELISA assay showed that S-MSCs provides abundant level of VEGF, PDGF, bFGF, IL-10 and TGFβ. In vivo administration of S-MSCs remarkably enhanced the Tarlov score. S-MSCs improved angiogenesis through enhancing VEGF gene expression and significantly increasing CD31 positive area in muscle tissue of PAD diabetic rats. Conclusion: Our findings suggest that S-MSCs could improves dynamic function and angiogenesis in PAD diabetic rats.

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Section: Discussionsupporting

confidence: 92%

“…It showed that the ligation action was successful. Physical impairment has also been shown by other studies with this experimental animal model ( 23 , 24 ).…”

Section: Discussionsupporting

confidence: 83%

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease

Sazli¹,

Lindarto²,

Hasan³

et al. 2023

Med Arch

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“…The series of pathological changes led to a decrease in nerve stem perfusion, resulting in the simultaneous reduction of nerve conduction velocity and oxygen tension. Angiogenesis is an important compensatory step in the body's response to hypoxia, it can induce neovascularization to reconstruct the vascular network and restore tissue blood supply (9). Intuitively, the researchers hope to improve nerve blood supply through angiogenesis caused by tissue hypoxia, but the role of angiogenesis in DPN has been somewhat contradictory, which is partly reflected in the unclear changes of vascular endothelial growth factor (VEGF), the most representative angiogenesis factor, in DPN (10).…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor levels in diabetic peripheral neuropathy: a systematic review and meta-analysis

et al. 2023

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ObjectiveVascular endothelial growth factors (VEGFs, including VEGF-A, VEGF-B, VEGF-C, VEGF-D and PLGF) have important roles in the development and function of the peripheral nervous system. Studies have confirmed that VEGFs, especially VEGF-A (so called VEGF) may be associated with the diabetic peripheral neuropathy (DPN) process. However, different studies have shown inconsistent levels of VEGFs in DPN patients. Therefore, we conducted this meta-analysis to evaluate the relationship between cycling levels of VEGFs and DPN.MethodsThis study searched 7 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and Chinese Biomedical Literature (CBM), to find the target researches. The random effects model was used to calculate the overall effect.Results14 studies with 1983 participants were included, among which 13 studies were about VEGF and 1 was VEGF-B, so only the effects of VEGF were pooled. The result showed that there were obviously increased VEGF levels in DPN patients compared with diabetic patients without DPN (SMD:2.12[1.34, 2.90], p<0.00001) and healthy people (SMD:3.50[2.24, 4.75], p<0.00001). In addition, increased circulating VEGF levels were not associated with an increased risk of DPN (OR:1.02[0.99, 1.05], p<0.00001).ConclusionCompared with healthy people and diabetic patients without DPN, VEGF content in the peripheral blood of DPN patients is increased, but current evidence does not support the correlation between VEGF levels and the risk of DPN. This suggests that VEGF may play a role in the pathogenesis and repairment of DPN.

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“…The elucidation of the molecular mechanisms regulating the pathological conditions responsible for the development of diseases could provide valuable information that could be useful in developing new methods for the management of these diseases. Many recent studies have shown that miRNAs are promising targets for the diagnosis and treatment of various conditions, including LEAD [ 49 , 50 , 51 , 52 , 53 , 54 ], AAA [ 28 , 55 , 56 , 57 ], and CVD [ 58 , 59 ]. In particular, many investigations were carried out to evaluate the utility of proangiogenic properties of miRNAs in the therapy of peripheral atherosclerosis [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, many investigations were carried out to evaluate the utility of proangiogenic properties of miRNAs in the therapy of peripheral atherosclerosis [ 52 ]. For example, adipose tissue mesenchymal stem cells transfected with miRNA-126 exhibit a promising therapeutic potential in the diabetic mouse model with critical limb ischemia [ 49 ]. The proangiogenic properties of miR-548j-5p have been demonstrated to exert a beneficial effect on hindlimb ischemia in mouse models [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

miRNA Regulatory Networks Associated with Peripheral Vascular Diseases

Zalewski

Ruszel

Stępniewski

et al. 2022

JCM

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A growing body of evidence indicates a crucial role of miRNA regulatory function in a variety of mechanisms that contribute to the development of diseases. In our previous work, alterations in miRNA expression levels and targeted genes were shown in peripheral blood mononuclear cells (PBMCs) from patients with lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and chronic venous disease (CVD) in comparison with healthy controls. In this paper, previously obtained miRNA expression profiles were compared between the LEAD, AAA, and CVD groups to find either similarities or differences within the studied diseases. Differentially expressed miRNAs were identified using the DESeq2 method implemented in the R programming software. Pairwise comparisons (LEAD vs. AAA, LEAD vs. CVD, and AAA vs. CVD) were performed and revealed 10, 8, and 17 differentially expressed miRNA transcripts, respectively. The functional analysis of the obtained miRNAs was conducted using the miRNet 2.0 online tool and disclosed associations with inflammation and cellular differentiation, motility, and death. The miRNet 2.0 tool was also used to identify regulatory interactions between dysregulated miRNAs and target genes in patients with LEAD, AAA, and CVD. The presented research provides new information about similarities and differences in the miRNA-dependent regulatory mechanisms involved in the pathogenesis of LEAD, AAA, and CVD.

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Angiogenesis in diabetic mouse model with critical limb ischemia; cell and gene therapy

Cited by 8 publications

References 52 publications

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease

Vascular endothelial growth factor levels in diabetic peripheral neuropathy: a systematic review and meta-analysis

miRNA Regulatory Networks Associated with Peripheral Vascular Diseases

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