Stem Cell-conditioned Medium Research Articles

Synergistic inhibitory effect of human umbilical cord matrix mesenchymal stem cells-conditioned medium and atorvastatin on MCF7 cancer cells viability and migration.

Recent studies have demonstrated inhibitory effects of mesenchymal stem cells on breast tumors. Likewise, the emerging interest in statins as anticancer agents is based on their pleiotropic effects. In the present study, we investigated whether atorvastatin and umbilical cord matrix derived mesenchymal stem cells-conditioned medium affect the MCF7 cancer cells viability and interactions. We measured the viability of MCF7 cancer cells by MTT assay, flow cytometry, and quantitative real-time PCR. Two-dimensional culture and hanging drop aggregation assay illustrated the morphological changes. We traced the MCF7 migration via scratch-wound healing test and trans-well assay. The results showed the inhibition of cancer cell viability in all treated groups compared to the control group. The effect of atorvastatin and conditioned medium combination was significantly more than each substance separately. The morphological changes indicated apoptosis in treated cells. The annexin V/PI flow cytometry especially in the combination-treated group displayed decreasing in DNA synthesis and cell cycle arrest in G1 and G2/M phases. As well, the mRNA expressions of caspases 3, 8, 9, and Bcl-2 genes were along with extrinsic and intrinsic apoptosis pathways. Conditioned medium disrupted the connections between cancer cells, so the spheroids in three-dimensional configuration lost their order and dispersed. The migration of treated cells across the wound area and trans-well diminished, particularly by the conditioned medium and atorvastatin combination. There fore, the synergistic anti-proliferative and anti-motility effect of atorvastatin along with human umbilical cord mesenchymal stem cells-derived conditioned medium on MCF7 breast cancer cells have been proved. The results might lead the development of novel adjuvant anticancer therapeutics based on targeting or modifying the extracellular matrix to increase chemotherapy results or to prevent metastatic colonization.Graphical abstract Schematic representation of “Synergistic Inhibitory Effect of Human Umbilical Cord Matrix Mesenchymal Stem Cells-Conditioned Medium and Atorvastatin on MCF7 Cancer Cells Viablity and Migration” by: Dr. Reyhaneh Abolghasemi, Dr. Somayeh Ebrahimi-barough, Proffesor. Jafar Ai.

Mesenchymal stem cell conditioned medium azacytidine, panobinostat and GSK126 alleviate TGF-β-induced EMT in lung cancer

This study aimed to investigate the effects of mesenchymal stem cells (MSCs) conditioned medium, azacytidine, panobinostat, and GSK126 on TGF-β-induced EMT in lung cancer. MSC were cultured in DMEM medium to make MSC conditioned medium. Our results showed that MSC conditioned medium, azacytidine, panobinostat and GSK126 reduced cell viability, invasion, expressions of N-cad, vimentin and α-SMA and increased E-cad expression in cells treated with TGF-β. MSC conditioned medium alleviated TGF-β-induced increases in cell viability and decrease in E-cad expression. In conclusion, MSC conditioned medium, azacytidine, panobinostat, and GSK126 could alleviate TGF-β-induced EMT in lung cancer.

In Vivo Effects of Conditioned Medium from Human Uterine Cervical Stem Cells in an Ovarian Cancer Xenograft Mouse Model.

Ovarian cancer is the most lethal of all gynecological cancers, despite advances in surgical techniques and medical treatments. During the last years, therapies based on mesenchymal stem cells and particularly their secretome (conditioned medium, CM) have emerged as promising treatments for various types of tumors. In the present study, we evaluated the in vivo antitumor effect of human uterine cervical stem cell conditioned medium (hUCESC-CM) after intraperitoneal administration in an ovarian cancer mouse model. We found that intraperitoneal injection of hUCESC-CM in immunodeficient mice, injected fifty days previously with the human ovarian adenocarcinoma SKOV-3 cell line, significantly reduced abdominal tumor growth, and significantly increased overall survival, compared to control mice. hUCESC-CM could be an alternative approach to intraperitoneal treatment of ovarian cancer, either administered alone and/or with conventional chemotherapy.

Neural stem cell-conditioned medium upregulated the PCMT1 expression and inhibited the phosphorylation of MST1 in SH-SY5Y cells induced by Aβ25-35

A progressive neurodegenerative disease, Alzheimer’s disease (AD). Studies suggest that highly expressed protein isoaspartate methyltransferase 1 (PCMT1) in brain tissue. In the current study, we explored the effects of neural stem cell-conditioned medium (NSC-CDM) on the PCMT1/MST1 pathway to alleviate Aβ25-35-induced damage in SH-SY5Y cells. Our data suggested that Aβ25-35 markedly inhibited cell viability. NSC-CDM or Neural stem cell-complete medium (NSC-CPM) had a suppression effect on toxicity when treatment with Aβ25-35, with a greater effect observed with NSC-CDM. Aβ25-35 + NSC-CDM group exhibited an increase in PCMT1 expression. sh-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM through the induction of apoptosis and improved p-MST1 expression. Overexpression of PCMT1 reversed the Aβ25-35-induced decrease in cell proliferation and apoptosis. In summary, our findings suggest that NSC-CDM corrects the Aβ25-35- induced damage to cells by improving PCMT1 expressions, which in turn reduces phosphorylation of MST1.

Neural stem cell-conditioned medium upregulated the PCMT1 expression and inhibited the phosphorylation of MST1 in SH-SY5Y cells induced by Aβ25-35

A progressive neurodegenerative disease, Alzheimer’s disease (AD). Studies suggest that highly expressed protein isoaspartate methyltransferase 1 (PCMT1) in brain tissue. In the current study, we explored the effects of neural stem cell-conditioned medium (NSC-CDM) on the PCMT1/MST1 pathway to alleviate Aβ25-35-induced damage in SH-SY5Y cells. Our data suggested that Aβ25-35 markedly inhibited cell viability. NSC-CDM or Neural stem cell-complete medium (NSC-CPM) had a suppression effect on toxicity when treatment with Aβ25-35, with a greater effect observed with NSC-CDM. Aβ25-35 + NSC-CDM group exhibited an increase in PCMT1 expression. sh-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM through the induction of apoptosis and improved p-MST1 expression. Overexpression of PCMT1 reversed the Aβ25-35-induced decrease in cell proliferation and apoptosis. In summary, our findings suggest that NSC-CDM corrects the Aβ25-35- induced damage to cells by improving PCMT1 expressions, which in turn reduces phosphorylation of MST1.

In vitro maturation medium supplementation: utilization of repaglinide, L-carnitine, and mesenchymal stem cell-conditioned medium to improve developmental competence of oocytes derived from endometriosis mouse models

Endometriosis (EMS) is one of the most prevalent causes for female infertility. Herein, we investigated the effect of the repaglinide (RG), L-carnitine (LC), and bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) supplementation during in vitro maturation (IVM) on the quality, maturation, and fertilization rates, as well as embryonic quality and development of oocytes derived from normal and EMS mouse model. Immature oocytes were collected from two groups of normal and EMS-induced female NMRI mice at 6-8 weeks of age. Oocytes were cultured in IVM medium unsupplemented (control group), or supplemented with 1 M RG, 0.3 and 0.6 mg/mL LC, and 25 and 50% BMSC-CM. After 24 h of oocyte incubation, IVM rate and antioxidant status were assessed. Subsequently, the rates of fertilization, cleavage, blastulation, and embryonic development were assessed. Our results demonstrated that supplementation of IVM medium with LC and BMSC-CM, especially 50% BMSC-CM, significantly enhanced IVM and fertilization rates, and markedly improved blastocyst development and total blastocyst cell numbers in EMS-induced mice compared to the control group (53.28±0.24 vs 18.09±0.10%). Additionally, LC and BMSC-CM were able to significantly modulate EMS-induced nitro-oxidative stress by boosting total antioxidant capacity (TAC) and mitigating nitric oxide (NO) levels. Collectively, LC and BMSC-CM supplementation improved oocyte quality and IVM rates, pre-implantation developmental competence of oocytes after in vitro fertilization, and enhanced total blastocyst cell numbers probably by attenuating nitro-oxidative stress and accelerating nuclear maturation of oocytes. These outcomes may provide novel approaches to refining the IVM conditions that can advance the efficiency of assisted reproductive technologies in infertile couples.

Comparative efficacy of topical Adipocyte-derived Mesenchymal Stem Cells-Conditioned Medium (ADMSC-CM) and Amniotic Membrane Mesenchymal Stem Cells-Conditioned Medium (AMSC-CM) on chronic plantar ulcers in leprosy: a randomized controlled trial

Introduction: Chronic Plantar Ulcer of Leprosy (CPUL), one of the debilitating disabilities and complications, poses a treatment challenge. Utilization of stem cells, specifically adipocyte-derived mesenchymal stem cells-conditioned medium (ADMSC-CM) and amniotic membrane mesenchymal stem cells-conditioned medium (AMSC-CM), may serve as a novel therapeutic option. This study aims to compare the efficacy of topical ADMSC-CM, topical AMSC-CM, and farmazertin gauze dressing (FGD) only on the healing of CPUL.Methods: In this randomized controlled trial, our study recruited 54 subjects with CPUL. Subjects were randomly assigned to topical ADMSC-CM (n = 16), topical AMSC-CM (n = 22), or FGD (n = 16) applied every three days for up to 8 weeks. Data were analyzed using SPSS version 20 for Windows.Results: Healing percentage increased each week in all groups. Statistic differences between groups (p <0.05) were observed for ulcer mean size and depth reduction from week three onwards. No adverse reactions or complications were reported. At the end of the study, based on clinically improved ulcers, topical ADMSC-CM (100.0%) were superior in improving the healing of CPULs compared to topical AMSC-CM (54.55%) and FGD only (50.0%).Conclusion: ADMSC-CM and AMSC-CM are potential therapeutic agents in the management of CPUL, with ADMSC-CM being superior in overall ulcer improvement.

Determination of Total Protein and Calcium in Gingival Mesenchymal Stem Cell-Conditioned Medium

Gingival mesenchymal stem cell-conditioned medium (GMSC-CM) is a conditioned medium obtained from cultured gingival mesenchymal stem cells. GMSCs are easily isolated from gingival tissue, whereas gingival tissue is easily obtained by minimally invasive techniques. On the other hand, CM contains proteins, cytokines, chemokines and growth factors that play an important role in osteogenic differentiation.This study aims to determine the total protein and calcium levels in GMSC-CM.GMSCs were grown in culture media with 10% of FBS. CM of GMSC was obtained from the media collection process with a 0.22 µm filter and concentrated with a centrifugal filter to obtain a concentrated GMSC-CM. The concentration of total protein was performed by bicinchoninic acid protein assay on GMSC-CM and concentrated GMSC-CM. Calcium level was performed by atomic absorption spectroscopy method. The results arethat GMSC-CM had a total protein concentration of 2502±0.06 µg/ml, and the concentratedGMSC-CM was 1.912±0.08 μg/ml.The calcium level of GMSC-CM was 0.009% and concentratedGMSC-CM was 0.009%. It can be concluded thatGMSC-CM had a high concentration of total protein and calcium. These parameters were used to develop bioprocesses to enhance the production of GMSC-CM, which will support the implementation of cell-free therapy for tissue regeneration.

Ameliorating Effect of Umbilical Cord Mesenchymal Stem Cells in a Human Induced Pluripotent Stem Cell Model of Dravet Syndrome.

Dravet syndrome (DS) is a form of severe childhood-onset refractory epilepsy typically caused by a heterozygous loss-of-function mutation. DS patient-derived induced pluripotent stem cells (iPSCs) are appropriate human cells for exploring disease mechanisms and testing new therapeutic strategies in vitro. Repeated spontaneous seizures can cause neuroinflammatory reactions and oxidative stress, resulting in neuronal toxicity, neuronal dysfunction, blood-brain barrier disruption, and hippocampal inflammation. Antiepileptic drug therapy does not delay the development of chronic epilepsy. The application of mesenchymal stem cells (MSCs) is one therapeutic strategy for thwarting epilepsy development. This study evaluated the effects of human umbilical cord mesenchymal stem cell-conditioned medium (HUMSC-CM) in a new in vitro model of neurons differentiated from DS patient-derived iPSCs. In the presence of HUMSC-CM, increases in superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), glutathione peroxidase (GPX), and glutathione (GSH) levels were found to contribute to a reduction in reactive oxygen species (ROS) levels. In parallel, inflammation was rescued in DS patient-derived neuronal cells via increased expression of anti-inflammatory cytokines (TGF-β, IL-6, and IL-10) and significant downregulation of tumor necrosis factor-α and interleukin-1β expression. The intracellular calcium concentration ([Ca2+]i) and malondialdehyde (MDA) and ROS levels were decreased in DS patient-derived cells. In addition, action potential (AP) firing ability was enhanced by HUMSC-CM. In conclusion, HUMSC-CM can effectively eliminate ROS, affect migration and neurogenesis, and promote neurons to enter a highly functional state. Therefore, HUMSC-CM is a promising therapeutic strategy for the clinical treatment of refractory epilepsy such as DS.

Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells.

The role of the epithelial–mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT. CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers. Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-β1. CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM. ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-β1 treatment. CSE or TGF-β1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent. Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke.

Protective effects of low-molecular-weight components of adipose stem cell-derived conditioned medium on dry eye syndrome in mice

The present study demonstrated the protective effects of low-molecular-weight adipose-derived stem cell-conditioned medium (LADSC-CM) in a mouse model of dry eye syndrome. Mice subjected to desiccating stress and benzalkonium chloride had decreased tear secretion, impaired corneal epithelial tight junction with microvilli, and decreased conjunctival goblet cells. Topical application of adipose-derived stem cell-conditioned medium (ADSC-CM) stimulated lacrimal tear secretion, preserved tight junction and microvilli of the corneal epithelium, and increased the density of goblet cells and MUC16 expression in the conjunctiva. The low-molecular-weight fractions (< 10 kDa and < 3 kDa) of ADSC-CM (LADSC-CM) provided better protections than the > 10 kDa or > 3 kDa fractions of ADSC-CM. In the in vitro study, desiccation for 10 min or hyperosmolarity (490 osmols) for 24 h caused decreased viability of human corneal epithelial cells, which were reversed by LADSC-CM. The active ingredients in the LADSC-CM were lipophobic and stable after heating and lyophilization. Our study demonstrated that LADSC-CM had beneficial effects on experimental dry eye. It is worthy of further exploration for the active ingredient(s) and the mechanism.

Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate

BackgroundVibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS‐MSC‐conditioned medium (CM) on V. cholerae LPS immunization in a murine model.MethodsAfter preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)).ResultsThe LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P < 0.001). TNF-α levels, in contrast to IL-10 and TGF-β, were reduced significantly in mice receiving the LPS + LPS-MSC-CM compared to mice receiving only LPS. IL-4, IL-5, and BAFF levels significantly increased in mice receiving increased doses of LPS + LPS-MSC-CM compared to those who received only LPS. The highest vibriocidal antibody titer (1:64) was observed in LPS + LPS-MSC-CM-immunized mice and resulted in a significant improvement in survival in infant mice infected by V. cholerae O1.ConclusionsThe LPS-MSC-CM modulates the immune response to V. cholerae LPS by regulating inflammatory and anti-inflammatory responses and inducing vibriocidal antibodies, which protect neonate mice against V. cholerae infection.

Investigation of Stem Cell Applications on In Vitro Fertilization in Rats

We aimed to search the effects of bone marrow-derived mesenchymal stem cell-conditioned media on in vitro fertilization by investigation of lifetime of germ cells cleavage, degeneration rates and embryo quality. For this purpose, firstly MSCs were isolated from femurs and tibias of the rat, and cells were cultured until the fourth passage. Sperm and oocytes were collected from male and female rats. Oocytes were added in Human Tubal Fluid Media (HTFM), Single Step Media (SSM), Alpha-MEM Media (AMM) and Bone Marrow-Derived Mesenchymal Stem Cell-Conditioned Media (CM). Thousand sperm were added into the media which including oocytes. Embryos were allowed to produce by IVF. The development of the embryos was followed until the 11th day, and the arrest, degeneration rates and alive embryos were established. The embryos reached 2, 4, 8, 16 cells stages and morula stage in the CM. While AMM had a negative effect on fertilization and embryo development, the most favourable effect was shown to be caused by CM in comparison with the other medias. These results have shown that the beneficial effects of CM in IVF would be a significant increase in the rate of fertility and development of embryos.

Adipose-Derived Mesenchymal Stem Cells-Conditioned Medium Modulates the Expression of Inflammation Induced Bone Morphogenetic Protein-2, -5 and -6 as Well as Compared with Shockwave Therapy on Rat Knee Osteoarthritis.

The dose-dependent effects of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) were compared with those of shockwave (SW) therapy in the treatment of early osteoarthritis (OA). Anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was performed in rats divided into sham, OA, SW, CM1 (intra-articular injection of 100 μL ADSC-CM into knee OA), and CM2 (intra-articular injection of 200 μL ADSC-CM) groups. Cartilage grading, grading of synovium changes, and specific molecular analysis by immunohistochemistry staining were performed. The OARSI and synovitis scores of CM2 and SW group were significantly decreased compared with those of the OA group (p < 0.05). The inflammatory markers interleukin 1β, terminal deoxynucleotidyl transferase dUTP nick end labeling and matrix metalloproteinase 13 were significantly reduced in the CM2 group compared to those in the SW and CM1 groups (p < 0.001). Cartilage repair markers (type II collagen and SRY-box transcription factor 9, SOX9) expression were significantly higher in the CM2 group than in the other treatment groups (p < 0.001; p < 0.05). Furthermore, inflammation-induced growth factors such as bone morphogenetic protein 2 (BMP2), BMP5, and BMP6 were significantly reduced in the treatment groups, and the CM2 group showed the best results among the treatments (p < 0.05). In conclusion, ADSC-CM and SW ameliorated the expression of inflammatory cytokines and inflammation-induced BMPs to protect the articular cartilage of the OA joint.

Immunolocalization of Steroidogenic Enzymes (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and P450scc) in Rats with Testicular Dysfunction Treated with Mesenchymal Stem Cells-conditioned Medium

About 60-80 million couples in the world are suffering from infertility disease. Infertility is a major problem in patients coping with chemotherapy. The chemotherapy process can degenerate non-target organs, especially in testes. Infertility in male or testicular dysfunction is caused by the failure of proliferation and differentiation of the spermatogenic cells. Many studies reported that mesenchymal stem cells-conditioned medium promoted regenerative processes. The present study aimed to investigate the effect of mesenchymal stem cells-conditioned medium on the cisplatin-induced testicular dysfunction by examining the immunolocalization of steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and P450scc which are considered as markers of steroid production. All experimental animals were divided into three groups, namely the control group, mesenchymal stem cells-conditioned medium treated group with an injection dose of 0.2 ml/kg body weight (BW, P1), and mesenchymal stem cells-conditioned medium treated group with an injection dose of 0.5 ml/kg BW (P2). Cisplatin was injected into both treated groups to induce testicular dysfunction. The testicular tissues were processed by the paraffin method, then cut to a thickness of 5 µm, followed by immunohistochemical staining. The HSD3B1 immunoreactivities were found only in Leydig cells, and the intensity increased every week after the injection of mesenchymal stem cells-conditioned medium. The variety of weeks and groups was significantly different in the number of immunoreactive cells of HSD3B1. The results indicated a significant difference between one week after the first injection and the one week after the third and fourth injection. The findings showed a significant difference between the treated group with an injection dose of 0.2 ml/kg BW and the control group. The number of immunoreactive cells of HSD3B1 with an injection dose of 0.5 ml/kg BW was greater compared to the group that received an injection dose of 0.2 ml/kg BW. The intensity of HSD3B1 and HSD17B1 increased every week. The p450scc immunoreactive cells were only found in Leydig cells. The intensity of positive cells of p450scc in the treated group with an injection dose of 0.5 ml/kg BW was more intense, compared to the treated group with an injection dose of 0.2 ml/kg BW. The results of the current study showed that the injection of mesenchymal stem cells-conditioned medium can improve the regeneration of spermatogenic cells, and recover spermatogenesis proved by positive cells of HSD3B1, HSD17B1, and p450scc as markers of steroid production.

The protective effects of neural stem cells and neural stem cells-conditioned medium against inflammation-induced prenatal brain injury

Intrauterine inflammation affects fetal development of the nervous system and may cause prenatal brain injury in offspring. Previously, neural stem cells have been extensively used as a therapeutic choice for nervous system diseases. Recently, the therapeutic ability of conditioned medium, harvested from cultured stem cells, has captured the attention of researchers in the field. Our study aimed to compare the therapeutic effect of neural stem cells (NSCs) or NSC-conditioned medium (NSC-CM) after prenatal brain injury. The animal model was induced by intraperitoneal injection of lipopolysaccharide into the pregnant mice and NSCs or NSC-CM were transplanted into the lateral ventricle of embryos in treatment groups. Inflammation and apoptosis were evaluated postpartum in offspring via measuring the expression of NLRP3 gene and protein, the expression and the activity of caspase-3, and the expression of pro-inflammatory cytokines by real-time PCR, immunohistochemistry, western blotting, ELISA, and colorimetric assay kit. A rotarod test was performed for motor function evaluation. Data showed that although NSC-CM fought against the inflammation and apoptosis and improved the motor function, NSCs acted more efficiently. In conclusion, the results of our study contend that NSCs have a better therapeutic effect than CM in prenatal brain injury.

1167P DIO2 is implicated in the antitumor effect of the lung embryonic stem cell conditioned medium and impacts prognosis in non-small cell lung cancer

Critical pathways are shared between embryogenesis and cancer; but while the first is an organized and well-regulated process, the last is characterized by entropy. Several works have evaluated the potential of the embryonic microenvironment for controlling tumor development, showing that embryonic stem cell conditioned media are able to reduce metastatic phenotype of cancer cells. In this context, we have previously observed that human embryonic mesenchymal lung cells-conditioned medium (hEML-CM) are able to induce differentiation in tumor cells.

Anti-aging effects of fetal dermal mesenchymal stem cells in a D-galactose-induced aging model of adult dermal fibroblasts.

The main characteristic of skin aging is the change in the composition of the dermis, mainly resulting from fibroblast senescence. Mesenchymal stem cells derived from fetal dermis are defined as fetal dermal mesenchymal stem cells; they reportedly exert wound healing effects on the skin and regulate keloid fibroblast proliferation. D-Galactose is widely used in animal aging models. In this study, we confirmed that D-galactose inhibits adult dermal fibroblast proliferation, and the inhibitory effect gradually increased with increasing concentration. Finally, we chose a concentration of 40g/L D-galactose to induce adult dermal fibroblast senescence. D-Galactose increased the intensity of senescence-associated β-galactosidase staining and the levels of reactive oxygen species in adult dermal fibroblasts. Furthermore, D-galactose increased the mRNA expression of p16, p21, and p53. The fetal dermal mesenchymal stem cell-conditioned medium improved the above-mentioned effects. Overall, fetal dermal mesenchymal stem cells exerted anti-aging effects against adult dermal fibroblasts induced by D-galactose via paracrine functions.

Mesenchymal stem cell-conditioned medium alleviates high fat-induced hyperglucagonemia via miR-181a-5p and its target PTEN/AKT signaling

Backgroundα-cell dysregulation gives rise to fasting and postprandial hyperglycemia in type 2 diabetes mellitus(T2DM). Administration of Mesenchymal stem cells (MSCs) or their conditioned medium can improve islet function and enhance insulin secretion. However, studies showing the direct effect of MSCs on islet α-cell dysfunction are limited. MethodsIn this study, we used high-fat diet (HFD)-induced mice and α-cell line exposure to palmitate (PA) to determine the effects of bone marrow-derived MSC-conditioned medium (bmMSC-CM) on glucagon secretion. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay(ELISA). To investigate the potential signaling pathways, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), AKT and phosphorylated AKT(p-AKT) were assessed by Western blotting. ResultsIn vivo, bmMSC-CM infusion improved the glucose and insulin tolerance and protected against HFD-induced hyperglycemia and hyperglucagonemia. Meanwhile, bmMSC-CM infusion ameliorated HFD-induced islet hypertrophy and decreased α- and β-cell area. Consistently, in vitro, glucagon secretion from α-cells or primary islets was inhibited by bmMSC-CM, accompanied by reduction of intracellular PTEN expression and restoration of AKT signaling. Previous studies and the TargetScan database indicate that miR-181a and its target PTEN play vital roles in ameliorating α-cell dysfunction. We observed that miR-181a-5p was highly expressed in BM-MSCs but prominently lower in αTC1-6 cells. Overexpression or downregulation of miR-181a-5p respectively alleviated or aggravated glucagon secretion in αTC1-6 cells via the PTEN/AKT signaling pathway. ConclusionsOur observations suggest that MSC-derived miR-181a-5p mitigates glucagon secretion of α-cells by regulating PTEN/AKT signaling, which provides novel evidence demonstrating the potential for MSCs in treating T2DM.

Adipose-derived stem/stromal cell secretome modulates breast cancer cell proliferation and differentiation state towards aggressiveness

It is becoming increasingly evident that mesenchymal stem/stromal cells are recruited by cancer cells from nearby endogenous host stroma and promote events such as tumor proliferation, angiogenesis, invasion, and metastasis, as well as mediate therapeutic resistance. Consequently, understanding the regulatory mechanisms of ASCs that influence the tumor microenvironment may provide an avenue for further treatment. To understand the role of the ASC secretome in breast cancer cell proliferation, death, and phenotype alteration, adipose-derived stem cell-conditioned medium (mASC) was used to cultivate MCF-7 and MDA-MB-231 cells. These breast cancer cells in mASC showed a shorter doubling time, higher frequency of EdU positivity, and higher levels of phosphorylated histone 3. In addition, increased expression of cyclin B1 was observed, suggesting that proliferation was induced. The mASC was also able to increase apoptosis in MCF-7 cells, which was confirmed by caspase-7 activation. The number of tumor-initiating cells (CD44+ CD24-/low) and migration capacity were increased in cells cultivated in mASC. These data collectively suggest that ASC-conditioned medium can induce selective pressure by increasing cell proliferation, giving rise to a more aggressive phenotype in MCF-7 and MDA-MB-231 cells. Our study provides a foundation for further elucidation of the precise mechanism underlying ASCs in breast cancer cells and the modulation of ASCs in potential therapeutic uses.