جستجوی مقالات مرتبط با کلیدواژه "secretome" در نشریات گروه "پزشکی"

Testicular ischemia/reperfusion injury, a significant result of testicular torsion, can lead to the risk of male infertility.

The current study aimed to evaluate the effect of human amniotic membrane-derived mesenchymal stem cells (hAMSCs) secretome on testicular torsion/detorsion (T/D) in mice.

All the experiments were performed in the Anatomy Department of Tehran University of Medical Sciences, Tehran, Iran, during the period of March 2023 to December 2023. 40 male NMRI mice (5-7 wk, 25-30 gr) were randomized into: 1) the sham group: mice received sham operations with no other interventions, 2) T/D group, 3) negative control group; torsion detorsion + intratesticular injection of Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12, and 4) the T/D group + hAMSCs secreted factors. Serum testosterone levels, hematoxylin and eosin staining, and sperm quality parameters were used to evaluate the therapeutic effects of hAMSCs secreted factors on the testicular structure and function. Tissue oxidative stress was measured by determining malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase-1. Nuclear factor erythroid 2-related factor 2, Kelch-like ECH-associated protein 1, NAD-dependent deacetylase sirtuin-1, tumor necrosis factor-alpha and tumor protein P53 mRNA expressions were assessed in testis via real-time polymerase chain reaction.

The results showed that hAMSCs secreted factors alleviated testicular T/D injury by attenuating oxidative stress, inflammatory response, and apoptosis via modulating the sirtuin-1/ nuclear factor erythroid 2-related factor 2/tumor necrosis factor-alpha signaling pathway.

hAMSCs secreted factors increased antioxidative, anti-inflammatory, and antiapoptotic properties which consequently increased testosterone levels, spermatogenesis, and sperm quality parameters.

One of the most common causes of global death is cardiovascular disease (CVD). Using mesenchymal stem cell (MSC) therapy for treating CVDs is revolutionizing regenerative medicine. Some challenges that have limited MSC therapy’s practical application include cell harvesting difficulty, ectopic transplantation, spontaneous differentiation to cartilage and bone, and possible immune responses following transplantation. MSCs release extracellular vesicles and biologically active molecules such as growth factors, chemokines, and cytokines, collectively called the secretome. Recent studies have shown that secretome administration could replace MSC transplantation. The secretome of MSCs plays a crucial role in controlling inflammatory reactions, enhancing tissue reperfusion by stimulating angiogenesis and vasculogenesis, preventing apoptosis and fibrosis development, and fostering the proliferation and differentiation of cardiac stem cells. This review discusses the current knowledge of MSC secretome application in cardiac regenerative medicine. It introduces possible approaches to improve cardiac recovery outcomes by utilizing the secretome in the clinic.

Skin aging is a degenerative process that can be induced by UV irradiation. UV radiation can produce reactive oxidate stress which causes premature aging. This study aims to examine the antiaging potential of secretome gel (SC) from human Wharton Jelly Mesenchymal Stem Cells (hWJ-MSCs) in a UVB-induced mice model. 

The secretome was obtained from hWJ-MSCs and made in gel form. Male mice were radiated by UVB for 15 min twice daily for 14 days. The gel was topically applied to the mice’s dorsal skin. Two treatments of secretome gel: secretome 1 is applied once and secretome 2 is applied twice daily after UVB radiation. TGF-β1, IL-10, and IL-18 gene expression was determined using RT-PCR. Hematoxylin Eosin staining was used to observe the inflammation and collagen density of skin tissue. An immunohistochemistry assay was used to analyze the protein expression of P53, COL4A1, MMP-2, and MMP-13. The data were statistically analyzed using the ANOVA test followed by the Tukey post hoc test (P<0.05). 

UVB induction caused loss of collagen, increasing inflammation and high expression of aging mediators. SC increased the gene expression of TGF-β1 and IL-10 and decreased IL-18 gene expression. Histopathological tests showed that SG increased collagen density, lowered inflammation, and repaired cell damage in skin tissue. Immunohistochemistry test showed that SC decreased MMP-2, MMP-13, and P53 expression, in contrast, increased COL4A1. 

The secretome gel of hWJ-MSCs showed antiaging activities with potential for preventing and curing skin aging.

Stem cell-derived secretome (SE) released into the extracellular space contributes to tissue repair. The present study aimed to investigate the impact of isolated secretome (SE) from adipose-derived mesenchymal stem cells (ASCs) on Leishmania major (L. major) lesions in BALB/c mice. 

This experimental study was conducted at Ahvaz University of Medical Sciences (Ahvaz, Iran) in 2021. Forty female BALB/c mice were infected with stationary phase promastigotes through intradermal injection in the bottom of their tail and randomly divided into four groups (n=10 per group). The mice were given SE (20 mg/mL), either alone or in combination with Glucantime (GC, 20 mg/mL/Kg), meglumine antimoniate (20 mg/mL/Kg) for the GC group, and phosphate-buffered saline (PBS) for the control group. After eight weeks, the lesion size, histopathology, the levels of Interleukin 10 (IL-10), and Interleukin 12 (IL-12) were assessed. For the comparison of values between groups, the parametric one-way ANOVA was used to assess statistical significance.

At the end of the experiment, the mice that received SE had smaller lesions (4.56±0.83 mm versus 3.62±0.59 mm, P=0.092), lower levels of IL-10 (66.5±9.7 pg/mL versus 285.4±25.2 pg/mL, P<0.001), and higher levels of IL-12 (152.2±14.2 pg/mL versus 24.2±4.4 pg/mL, P<0.001) than the control. Histopathology findings revealed that mice treated with SE had a lower parasite burden in lesions and spleen than the control group. 

The current study demonstrated that ADSC-derived SE could protect mice infected with L. major against leishmaniasis.

 The main reason for treatment failure and the primary cause of breast cancer deaths is metastasis. Cancer features, such as epithelial to mesenchymal transition (EMT), invasiveness, stemness, and ability to metastasize, are significantly influenced by oxidative stress.

 The primary objective of this work was to evaluate the effects of human Wharton’s jelly mesenchymal stem cell secretomes (hWJMSCs-Se) on oxidant contents and development of the breast cancer SK-BR3 cell line and alterations in EMT markers genes after treatment.

 SK-BR3 cells received 48 hours of treatment with 10, 25, or 50 μg/mL hWJMSCs-Se. The MTT test and colony formation were used to evaluate the SK-BR3 cells’ viability and proliferation capability. By using annexin V/propidium iodide (PI) staining, apoptosis was determined. The messenger ribonucleic acid (mRNA) expression levels in genes associated with antioxidants were additionally assessed. Antioxidant enzyme activity was checked after SK-BR3 treatment with hWJMSCs-Se.

 In the hWJMSCs-Se-treated SK-BR3 cells, colony counts, and viability percentages decreased significantly with time and concentration. The treated cells displayed considerably greater apoptotic indices when compared to the control. Catalase (CAT), superoxide dismutase (SOD) activities, and glutathione (GSH) content were significantly greater in the hWJMSCs-Se-exposed SK-BR3 cells. The Vimentin gene and N-cadherin gene were significantly elevated in the treated cells, and E-cadherin and β-catenin decreased conversely.

 The present study suggests that the use of hWJMSCs in the treatment of human epidermal growth factor receptor 2 (HER2)-positive malignancies provides an innovative solution for cancer therapy. As the oxidant level and EMT pathway decreased, breast cancer cell growth was significantly restricted, and mortality increased.

In order to treat a rat model of rotator cuff rupture, this work concentrated on the expression of TNMD and RUNX2, followed by rotator cuff repair and secretome-hMSCs.

A total of thirty 10-weeks-old male Sprague–Dawley rats were separated into five groups randomly, RC on week 0, lesion treated with a rotator cuff repair and saline (RC + NaCl group, n = 6) for 2 and 8 weeks, and lesion treated with a rotator cuff repair and secretome-hMSCs (RC + secretome-hMSC group, n = 6) for 2 and 8 weeks. The supraspinatus and infraspinatus muscle–tendon units were obtained for histological and biomechanical investigation at 0, 2 and 8 weeks following injury.

The findings showed that, in comparison with the RC + NaCl group, secretome-hMSCs significantly improved tendon repair by upregulating TNMD and RUNX2 expression and histology score.

Combining Secretome-hypoxia MSCs with RC healing may help rats with rotator cuff tears. 

The secretome of stem cells consists of a spectrum of bioactive factors secreted by stem cells grown in culture mediacytokines, chemokines, and growth factors in addition to extracellular vesicles (exosomes and microvesicles). Ease of handling and storage of secretomes along with their bioactivity towards processes in skin aging and customizability makes them an appealing prospective therapy for skin aging. This systematic review aims to investigate the potential usage of ascorbic acid (AA)-supplemented stem cell secretomes (SCS) in managing skin aging. We extracted articles from three databases: PubMed, Scopus, and Cochrane. This review includes in vitro, in vivo, and clinical studies published in English that discuss the correlation of AA-supplemented-SCS with skin aging. We identified 1111 articles from database and non-database sources from which nine studies met the inclusion criteria. However, the study results were less specific due to the limited amount of available research that specifically assessed the effects of AAsupplemented SCS in skin aging. Although further studies are necessary, the AA modification of SCS is a promising potential for improving skin health.

 Recent studies have demonstrated that adipose mesenchymal stem cells (AMSCs)-derived secretome (AMSC-Se) has anticancer impacts.

 This study investigated the cytotoxic impacts of AMSC-Se on a colon carcinoma cell (HT-29) line.

 The colon cancer cells were exposed to 50 or 100 µg/mL ASMC-Se for 24 hours. MTT test had used to examine the impacts of ASMC-Se on the survival rates of the cells. Caspase activity, mRNA, and protein expression of Bax and Bcl-2 had evaluated to determine apoptosis.

 ASMC-Se could diminish the survival of the cells concentration-dependently. The mRNA and protein expression of Bax was concentration-dependently elevated, while Bcl-2 expression decreased in the ASMC-Se group compared to the control concentration-dependently (P < 0.05). The caspase-3 and caspase-9 activities were concentration-dependently enhanced (P < 0.05), while the caspase-8 activity did not change with the AMSC-Se.

 These findings indicate that AMSC-Se effectively prevents cell growth and induces apoptosis by stimulating the intrinsic apoptotic pathway in these cells.

 Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to neuronal cell death and manifested by cognitive disorders and behavioral impairment. Mesenchymal stem cells (MSCs) are one of the most promising candidates to stimulate neuroregeneration and prevent disease progression. Optimization of MSC culturing protocols is a key strategy to increase the therapeutic potential of the secretome.

 Here, we investigated the effect of brain homogenate of a rat model of AD (BH-AD) on the enhancement of protein secretion in the secretome of periodontal ligament stem cells (PDLSCs) when cultured in a 3D environment. Moreover, the effect of this modified secretome was examined on neural cells to study the impact of the conditioned medium (CM) on stimulation of regeneration or immunomodulation in AD.

 PDLSCs were isolated and characterized. Then, the spheroids of PDLSCs were generated in a modified 3D culture plate. PDLSCs-derived CM was prepared in the presence of BH-AD (PDLSCs-HCM) and the absence of it (PDLSCs-CM). The viability of C6 glioma cells was assessed after exposure to different concentrations of both CMs. Then, a proteomic analysis was performed on the CMs.

 Differentiation into adipocytes and high expression of MSCs markers verified the precise isolation of PDLSCs. The PDLSC spheroids were formed after 7 days of 3D culturing, and their viability was confirmed. The effect of CMs on C6 glioma cell viability showed that both CMs at low concentrations (> 20 mg/mL) had no cytotoxic effect on C6 neural cells. The results showed that PDLSCs-HCM contains higher concentrations of proteins compared to PDLSCs-CM, including Src-homology 2 domain (SH2)-containing PTPs (SHP-1) and muscle glycogen phosphorylase (PYGM) proteins. SHP-1 has a role in nerve regeneration, and PYGM is involved in glycogen metabolism.

 The modified secretome derived from 3D cultured spheroids of PDLSCs treated by BH-AD as a reservoir of regenerating neural factors can serve as a potential source for AD treatment.

Diabetes is one of the metabolic diseases characterized by hyperglycemia, with many complications. Diabetic foot ulcer (DFU) is a significant complication of diabetes. Various therapy procedures have been recently described for DFU improvement.

Using PubMed, Scopus, Science Direct, and Google Scholar to discover the therapeutic effects of bee products, this review study was conducted in 2018-2019 by searching PubMed, Scopus, Science Direct, and Google Scholar databases.

Cell therapies with various cell candidates such as mesenchymal stem cells (MSCs) are increasingly introduced into routine medical care to manage skin wounds. The applying of these cells for tissue regeneration was initially based on the capability of MSCs to differentiate into specialized cells within the injured tissue. Paracrine signaling and differentiation mechanisms have both been contributed to improving tissue repair by MCSs. However, the role of MSCs differentiation is less due to the poor survival of these cells at the site of injury.

At the same time, paracrine signaling or their secretome is the primary mechanism of MSCs that stimulate neovascularization and re-epithelialization and mobilization of inhabitant stem cells. In this review study, we discuss the role of MSCs and their secretome that can improve the use of this new approach in treating ulcers and DFU.

Recent studies have shown that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have several drawbacks in treating critical-sized bone defect (CSD). Secretome may offer considerable advantages over living cells in terms of potency, manufacturing and storing easiness, and potential as a ready-to-go osteoinductive agent. However, thus far, there are no studies regarding the efficacy of secretome in bone healing. The objective of this study is to investigate the effect of the secretome in rat models with CSD. This was an experimental study with post-test only control group design using 60 skeletally mature Sprague Dawley rat which was divided evenly into 5 treatment groups (MSC only, Secretome only, MSC + Secretome, MSC + Secretome + BMP-2, Control group using Normal Saline). We used Bone Marrow derived MSC in this research. The critical-sized bone defect was created by performing osteotomy and defect was treated according to the groups. Rats were sacrificed on 2nd and 4th week and we measured the radiological outcome using Radiographic Union Score for Tibia (RUST) and histomorphometric (callus, osseous, cartilage, fibrous, and void area) evaluation using Image J. There was no difference in the weight of rats between groups before and after the intervention. RUST score in all intervention group is significantly higher than the control group, however, the MSC-only group was not statistically significant higher than the control group. There is no statistically significant difference in RUST Score between intervention groups. Histomorphometric evaluation showed that total callus formation is the widest in the MSC+Secretome+BMP-2 combination group while the osseous area is found highest on the secretome-only group. Secretome, whether used solely or combined with BM-MSC and BMP-2, is a novel, potent bone-healing agent for CSD in rat models. Level of evidence: V

Controversial results have been reported regarding the anti-tumor properties of extracellular vesicles derived from mesenchymal stem cells (MSCs). The present study was conducted to evaluate whether secretome derived from Human Wharton’s jelly mesenchymal stem cells (hWJMSCs) may stimulate or inhibit breast cancer growth in vitro and in vivo. MTT assays was performed to determine anti-tumor effects of hWJMSCs-secretome on both MCF-7 and 4T1 tumor cells in vitro. Afterward, 4T1 breast tumors were established in different groups of Balb/C mice (12 mice/group). The tumor sizes were monitored in different treatment groups and at day 30 post-tumor inoculation (PTI), blood samples were obtained and 6 mice of each group were sacrificed for hematological and histopathological assays. The rest of the mice in each group (n=6) were left alive up to day 120 PTI to determine survival rate. We found that hWJMSCs-secretome can inhibit growth of MCF-7 and 4T1 tumor cell lines in vitro. Moreover, intratumoral administration of hWJMSCs-secretome resulted in significant tumor growth inhibition and improvement of hematological indices in vivo and prolonged survival rate of tumor bearing mice. According to our findings, hWJMSCs-secretome could be considered a potent anti-tumor agent, however, further investigation should be done on other cancer models.

Several attempts have been made to identify the mechanisms by which mesenchymalstem cells (MSCs)-derived secretome exert anti-tumor or tumorigenic effects, but still furtherinvestigations are needed to explore this subject. Thus, in this study we want to examine theexpression of different cytokines in secretome of hWJ-MSCs and their effects on cytokineexpression profile of the MCF-7 tumor cells.

The hWJ-MSCs were isolated and characterized according to the International Societyfor Cellular Therapy criteria. Then, secretome of hWJ-MSCs was collected and freeze-dried, and20 mg/mL of the freeze-dried secretome was used to treat MCF-7 cancer cells for 48 hours.Afterwards, the expression levels of 12 cytokines including IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-8,IL-10, IL-12, IL-17A, TNFα, IFNγ and GM-CSF in secretome of hWJ-MSCs alone as well as insupernatant of tumor cells before and after treatment with hWJ-MSCs secretome were evaluated.

Our results indicate that MCF-7 cells express significant amount of IL-6 and IL-8.Moreover, significant amounts of IL-1a, IL-1b, IL-8, IL-6 and GM-CSF were detected in secretomeof hWJ-MSCs. Furthermore, IL-1a, IL-2 and IL-4 were expressed significantly by MCF-7 cellsafter their treatment with hWJ-MSCs-derived secretome.

According to our findings, the hWJ-MSCs derived secretome contains differentcytokines which can exert either anti-tumor or tumorigenic effects.