scholarly journals Antioxidative Capacity of Liver- and Adipose-Derived Mesenchymal Stem Cell-Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Mohamed M. Elshemy ◽  
Medhat Asem ◽  
Khaled S. Allemailem ◽  
Koichiro Uto ◽  
Mitsuhiro Ebara ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Stem Cell ◽  
Growth Factors ◽  
Mesenchymal Stem Cell ◽  
Angiogenic Factors ◽  
Conditioned Media ◽  
Therapeutic Effects ◽  
Differentiation Potential

Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance and impaired insulin secretion, which cannot be reversed with existing therapeutic strategies. Using mesenchymal stem cells (MSCs), cell-based therapy has been demonstrated in displaying therapeutic effects in T2DM for their self-renewable, differentiation potential, and immunosuppressive properties and higher levels of angiogenic factors. Stem cell therapies are complicated and have a serious adverse effect including tumor formation and immunogenicity, while using mesenchymal stem cell-conditioned media (MSC-CM) significantly reduces stem cell risk, maintaining efficacy and showing significantly higher levels of growth factors, cytokines, and angiogenic factors that stimulate angiogenesis and promote fracture healing in diabetes. In the present study, we investigated the therapeutic potential of the liver and adipose MSC-CM in diabetic endothelial dysfunction compared with standard insulin therapy. Fifty adult male Sprague Dawley rats were divided equally into 5 groups as follows: control, diabetic, diabetic+insulin, diabetic+liver MSC-CM, and diabetic+adipose MSC-CM; all treatments continued for 4 weeks. Finally, we observed that liver MSC-CM therapy had the most apparent improvement in levels of blood glucose; HbA1c; AGEs; lipid panel (cholesterol, TG, LDL, HDL, and total lipids); renal function (urea, uric acid, creatinine, and total protein); liver function (AST, ALT, ALP, bilirubin, and albumin); CPK; C-peptide; HO-1; inflammatory markers including IL-6, TNF-α, and CRP; growth factors (liver and serum IGF-1); amylase; histopathological changes; pancreatic cell oxidative stress; and antioxidant markers (MDA, GSH, ROS, CAT, SOD, HO-1, and XO) toward the normal levels compared with insulin and adipose MSCs-CM. Moreover, both the liver and adipose MSC-CM relieved the hyperglycemic status by improving pancreatic islet β cell regeneration, promoting the conversion of alpha cells to beta cells, reducing insulin resistance, and protecting pancreatic tissues against oxidative stress-induced injury as well as possessing the ability to modulate immunity and angiogenesis. These results indicated that MSC-CM infusion has therapeutic effects in T2DM rats and may be a promising novel therapeutic target.

scholarly journals Effects of Mesenchymal Stem Cell-derived Exosomes on Oxidative Stress Responses in Skin Cells

2021 ◽  
Author(s):  
Takaaki Matsuoka ◽  
Keita Takanashi ◽  
Katsuaki Dan ◽  
Kenichi Yamamoto ◽  
Koji Tomobe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cellular Senescence ◽  
Stress Responses ◽  
Dermal Fibroblasts ◽  
Skin Fibroblasts ◽  
Therapeutic Effects ◽  
P53 Expression ◽  
Before And After

Abstract Background: The mechanism by which reactive oxygen species (ROS) produced by oxidative stress promote cellular senescence has been studied in detail. This study aimed to verify the preventive or therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Ex) on the production of ROS induced by oxidative stress in human skin fibroblasts and clarify the mechanisms that promote cellular senescence.Methods: In a system where H2O2 was applied to skin fibroblasts, we assessed the effects of the application of MSC-Ex before and after oxidative stress and measured the fluctuations in several signaling molecules involved in subsequent intracellular stress responses. Exosomes were isolated from MSCs (MSC-Ex) and normal human dermal fibroblasts (NHDFs, NHDF-Ex) before and after exposure to H2O2. NHDFs were treated with exosomes before and after exposure to H2O2.Results: mRNA expression (aquaporin-1 and aquaporin-3) and hyaluronan secretion associated with skin moisturization were reduced by H2O2 treatment, whereas MSC-Ex reversed these effects. The cellular senescence induced by H2O2 was also reproduced in fibroblasts. Specifically, the downregulation of SIRT1 led to increased acetylated p53 expression over time, which induced the expression of p21, a downstream molecule of p53, and arrested the cell cycle, leading to cell senescence. MSC-Ex enhanced these signal transduction systems. MSC-Ex was also effective at blocking the increase of β-galactosidase activity and accumulation of ROS in cells. This effect was stronger than that of NHDF-Ex.Conclusion: MSC-Ex were found to act defensively against epidermal and cellular senescence induced by oxidative stress.

scholarly journals Dental Pulp Mesenchymal Stem Cells Attenuate Limb Ischemia via Promoting Capillary Proliferation and Collateral Development in a Preclinical Model

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Youfeng Li ◽  
Yuning Zhang ◽  
Hua Wang ◽  
Chengfeng Sun ◽  
Dongmei Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Dental Pulp ◽  
Inflammatory Responses ◽  
Limb Ischemia ◽  
Angiogenic Factors ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Collateral Development

Critical limb ischemia (CLI), an end-stage manifestation of peripheral artery disease (PAD), still lacks effective therapeutic strategies. Recently, dental pulp-derived mesenchymal stem cells (DP-MSCs) have been attracting more and more attentions in therapeutic applications due to their high proliferation ability, powerful osteogenic differentiation potential, and effective anti-inflammatory effects. In this study, we compared the therapeutic effects of MSCs derived from different sources in a femoral artery-ligated preclinical ischemic model. We found that treatments with MSCs, including bone marrow- (BM-), adipose- (AD-), dental pulp- (DP-), and umbilical cord- (UC-) derived MSCs, improved limb functions, reduced inflammatory responses, increased angiogenesis, and promoted regeneration of muscle fiber. Among them, DP-MSCs and BM-MSCs produced much more impressive effects in restoring limb functions and promoting angiogenesis. The flow velocity restored to nearly 20% of the normal level at 3 weeks after treatments with DP-MSCs and BM-MSCs, and obvious capillary proliferation and collateral development could be observed. Although neovascularization was induced in the ischemic limb after ligation, MSCs, especially DP-MSCs, significantly enhanced the angiogenesis. In vitro experiments showed that serum deprivation improved the expression of angiogenic factors, growth factors, and chemokines in DP-MSCs and UC-MSCs, but not in BM-MSCs and AD-MSCs. However, DP-MSCs produced stronger therapeutic responses than UC-MSCs, which might be due to the higher expression of hepatocyte growth factor (HGF) and hypoxia-inducible factor-1 α (HIF-1α). We speculated that DP-MSCs might stimulate angiogenesis and promote tissue repair via expressing and secreting angiogenic factors, growth factors, and chemokines, especially HGF and HIF-1α. In conclusion, DP-MSCs might be a promising approach for treating CLI.

scholarly journals Emerging Antioxidant Paradigm of Mesenchymal Stem Cell-Derived Exosome Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Chen Xia ◽  
Zhanqiu Dai ◽  
Yongming Jin ◽  
Pengfei Chen
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Direct Reduction ◽  
Antioxidant Properties ◽  
Therapeutic Effects ◽  
Diverse Range ◽  
Anti Inflammatory

Mesenchymal stem cell-derived exosomes have been under investigation as potential treatments for a diverse range of diseases, and many animal and clinical trials have achieved encouraging results. However, it is well known that the biological activity of the exosomes is key to their therapeutic properties; however, till date, it has not been completely understood. Previous studies have provided different explanations of therapeutic mechanisms of the exosomes, including anti-inflammatory, immunomodulatory, and anti-aging mechanisms. The pathological effects of oxidative stress often include organ damage, inflammation, and disorders of material and energy metabolism. The evidence gathered from research involving animal models indicates that exosomes have antioxidant properties, which can also explain their anti-inflammatory and cytoprotective effects. In this study, we have summarized the antioxidant effects of exosomes in in vivo and in vitro models, and have evaluated the anti-oxidant mechanisms of exosomes by demonstrating a direct reduction in excessive reactive oxygen species (ROS), promotion of intracellular defence of anti-oxidative stress, immunomodulation by inhibiting excess ROS, and alteration of mitochondrial performance. Exosomes exert their cytoprotective and anti-inflammatory properties by regulating the redox environment and oxidative stress, which explains the therapeutic effects of exosomes in a variety of diseases, mechanisms that can be well preserved among different species.

scholarly journals Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ning Li ◽  
Yichi Zhang ◽  
Narayan Nepal ◽  
Guoqing Li ◽  
Ningning Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ulcerative Colitis ◽  
Body Weight ◽  
Stem Cell ◽  
Dental Pulp ◽  
The Other ◽  
Therapeutic Effects ◽  
Colon Injury ◽  
Treatment Groups ◽  
Hepatocyte Growth

Abstract Background Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies. Dental pulp stem cell (DPSC) transplantation has been proposed as a potential therapy for UC. This study aimed to investigate the therapeutic effects of the rat hepatocyte growth factor (HGF) gene transduced into DPSCs for UC. Methods The therapeutic effects of HGF-DPSCs transplanted intravenously into a rat model of UC induced by 5% dextran sulphate sodium (DSS) were compared with the other treatment groups (LV-HGF group, DPSCs group and GFP-DPSCs group). Immunofluorescence and immunohistochemistry were used to observe the localization and proliferation of HGF-DPSCs at the site of colon injury. The expression levels of inflammatory factors were detected by real-time quantitative PCR (RT-PCR) and western blotting. The oxidative stress markers were detected by ELISA. DAI scores and body weight changes were used to macroscopically evaluate the treatment of rats in each group. Results Immunofluorescence and immunohistochemistry assays showed that HGF-DPSCs homed to colon injury sites and colocalized with intestinal stem cell (ISC) markers (Bmi1, Musashi1 and Sox9) and significantly promoted protein expression (Bmi1, Musashi1, Sox9 and PCNA). Anti-inflammatory cytokine (TGF-β and IL-10) expression was the highest in the HGF-DPSCs group compared with the other treatment groups, while the expression of pro-inflammatory cytokines (TNF-α and INF-γ) was the lowest. Additionally, the oxidative stress response results showed that malondialdehyde (MDA) and myeloperoxidase (MPO) expression decreased while superoxide dismutase (SOD) expression increased, especially in the HGF-DPSCs group. The DAI scores showed a downward trend with time in the five treatment groups, whereas body weight increased, and the changes were most prominent in the HGF-DPSCs group. Conclusions The study indicated that HGF-DPSCs can alleviate injuries to the intestinal mucosa by transdifferentiating into ISC-like cells, promoting ISC-like cell proliferation, suppressing inflammatory responses and reducing oxidative stress damage, which provides new ideas for the clinical treatment of UC.

Enhancing therapeutic effects and in vivo tracking of adipose tissue derived mesenchymal stem cells for liver injury using bioorthogonal click chemistry

Nanoscale ◽  
2020 ◽  
Author(s):  
Naishun Liao ◽  
Da Zhang ◽  
Ming Wu ◽  
Huang-Hao Yang ◽  
Xiaolong Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Liver Injury ◽  
Mesenchymal Stem Cell ◽  
Liver Diseases ◽  
Therapeutic Effects

Adipose tissue derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to low hepatic engraftment efficiency of...

Mesenchymal Stromal (stem) Cell (MSC) therapy modulates miR-193b-5p expression to attenuate sepsis-induced acute lung injury

2021 ◽  
pp. 2004216
Author(s):  
Claudia C. dos Santos ◽  
Hajera Amatullah ◽  
Chirag M. Vaswani ◽  
Tatiana Maron-Gutierrez ◽  
Michael Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lung Injury ◽  
Conditioned Media ◽  
Therapeutic Effects ◽  
Host Immune System ◽  
Gene And Protein Expression ◽  
Stromal Stem Cell ◽  
Mesenchymal Stromal Stem Cell ◽  
Deficient Mice

Although mesenchymal stromal (stem) cell (MSC) administration attenuates sepsis-induced lung injury in pre-clinical models, the mechanism(s) of action and host immune system contributions to its therapeutic effects, remain elusive. We show that treatment with MSCs decreased expression of host-derived microRNA (miR)-193b-5p and increased expression of its target gene, the tight junctional protein occludin (Ocln), in lungs from septic mice. Mutating the Ocln 3′ UTR miR-193b-5p binding sequence impaired binding to Ocln mRNA. Inhibition of miR-193b-5p in human primary pulmonary microvascular endothelial cells (HPMECs) prevents tumor necrosis factor (TNF)-induced decrease in Ocln gene and protein expression and loss of barrier function. MSC conditioned media mitigated TNF-induced miR-193b-5p upregulation and Ocln downregulation in vitro. When administered in vivo, MSC conditioned media recapitulated the effects of MSC administration on pulmonary miR-193b-5p and Ocln expression. MiR-193b deficient mice were resistant to pulmonary inflammation and injury induced by LPS instillation. Silencing of Ocln in miR-193b deficient mice partially recovered the susceptibility to LPS-induced lung injury. In vivo inhibition of miR-193b-5p protected mice from endotoxin-induced lung injury. Finally, the clinical significance of these results was supported by the finding of increased miR-193b-5p expression levels in lung autopsy samples from Acute Respiratory Distress Syndrome patients who died with diffuse alveolar damage.

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