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Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.
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Objective To investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) for radiation-induced lung injury (RILI) and the underlying mechanism. Methods Forty-five healthy adult male C57BL/6 mice were randomly divided into control, model, and BMSCs groups. The model and BMSCs groups received a single irradiation dose of 20 Gy to the chest, while the control group did not receive X-ray irradiation. For the BMSCs group, an injection of 1 × 106 BMSCs cells was administered via the tail vein within 6 h after irradiation. In the 5th week, the lung tissue was taken to observe pathological changes with HE staining; examine the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) with immunohistochemical staining; observe the polarization of macrophages with immunofluorescence staining; and measure the expression of the epithelial-mesenchymal transition markers E-cadherin, N-cadherin, and vimentin proteins by Western blot. Results After radiation, the model group developed pulmonary vasodilation and congestion with septal thickening and inflammatory cell infiltration, and these changes were markedly reduced in the BMSCs group. The model group showed significantly down-regulated expression of IL-6 and TNF-α compared with significantly increased levels in the model group (P < 0.01, P < 0.05). Treatment with BMSCs significantly increased the polarization of lung macrophages towards the M2 type, while significantly decreasing the abnormally increased N-cadherin and vimentin levels in RILI mice (P < 0.05, P < 0.01). Conclusion BMSCs have therapeutic effects for RILI mice, which may be through promoting macrophage polarization from M1 to M2.
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Islet transplantation is considered as one of the most effective approach for type 1 diabetes mellitus, although its efficacy is limited by several factors. Anoxia, stress and rejection occurring during the isolation, culturing and transplantation of islets may have impact on the outcome of the islet transplantation. Due to the biological properties such as anti-inflammation, angiogenetic promotion and immune regulation, mesenchymal stem cells (MSCs) are all the way focused by researchers. Additionally, exosome, a derivative of MSC, also plays an import role in regulating anoxia-induced oxidative stress modulation, angiogenetic promotion, and immune regulation. MSC-based islet transplantation may be a useful therapeutic tool in treating type 1 diabetes. Therefore, in this review, the potential effect of MSC prior and posterior to the operation of the islet transplantation, its clinical application as well as its limitations were reviewed, aiming to offer insights into the future application of islet transplantation in treating type 1 diabetes.
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Objective To investigate the isolation and culture of porcine bone marrow mesenchymal stem cell (BMSC) with α-1, 3-galactosyltransferase (GGTA1) gene knockout (GTKO), GTKO/ human CD46 (hCD46) insertion and cytidine monopho-N-acetylneuraminic acid hydroxylase (CMAH)/GGTA1 gene knockout (Neu5GC/Gal), and the protective effect of co-culture with porcine islets on islet cells. Methods Bone marrow was extracted from different transgenic pigs modified with GTKO, GTKO/hCD46 and Neu5GC/Gal. Porcine BMSC were isolated by the whole bone marrow adherent method and then cultured. The morphology of BMSC was observed and the surface markers of BMSC were identified by flow cytometry. Meantime, the multi-directional differentiation induced by BMSC was observed, and the labeling and tracing of BMSC were realized by green fluorescent protein (GFP) transfection. The porcine BMSC transfected with GFP were co-cultured with porcine islet cells. Morphological changes of porcine islet cells were observed, and compared with those in the porcine islet cell alone culture group. Results BMSC derived from pigs were spindle-shaped in vitro, expressing biomarkers of CD29, CD44, CD73, CD90, CD105 and CD166 rather than CD34 and CD45. These cells were able to differentiate into adipocytes, osteoblasts and chondrocytes. Porcine BMSC with GFP transfection could be labeled and traced, which could be stably expressed in the daughter cells after cell division. Porcine BMSC exerted certain protective effect on islet cells. Conclusions GFP-labeled porcine BMSC modified with GTKO, GTKO/hCD46 and Neu5GC/Gal are successfully established, which exert certain protective effect upon islet cells.
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BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.
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Neomycin/metabolism , Neomycin/toxicity , Exosomes/metabolism , Autophagy/physiology , Hair Cells, AuditoryABSTRACT
BackgroundType 1 diabetes is caused by a chronic immune response that destroys islet beta cells， resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However， little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells （GMSCs） in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes. MethodsWe injected human GMSCs into NOD mice to observe the trend of blood glucose， observed the survival of pancreatic β-cells by immunohistochemistry， and detected the change of immune cells in the spleen of mice by flow analysis. Finally， the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice. ResultsGMSCs significantly reduced the incidence of diabetes in NOD mice， with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group， P=0.013. The percentage of Follicular B cells（FO B cell） in the spleen of GMSCs-treated mice decreased from （52.2±4.1）% to （43.2±5.3）%， P=0.008， while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells， which could continuously produce insulin to control blood glucose. Finally， we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice. ConclusionGMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.
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As a crucial regulatory molecule in the context of vascular stenosis, transforming growth factor-β (TGF-β), plays a pivotal role in its initiation and progression. TGF-β, a member of the TGF-β superfamily, can bind to the TGF-β receptor and transduce extracellular to intracellular signals through canonical Smad dependent or noncanonical signaling pathways to regulate cell growth, proliferation, differentiation, and apoptosis. Restenosis remains one of the most challenging problems in cardiac, cerebral, and peripheral vascular disease worldwide. The mechanisms for occurrence and development of restenosis are diverse and complex. The TGF-β pathway exhibits diversity across various cell types. Hence, clarifying the specific roles of TGF-β within different cell types and its precise impact on vascular stenosis provides strategies for future research in the field of stenosis.
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Humans , Transforming Growth Factor beta/metabolism , Constriction, Pathologic , Signal Transduction , Cell Differentiation , Vascular Diseases , Transforming Growth Factors , Transforming Growth Factor beta1ABSTRACT
Objective:To explore whether the electroacupunture stimulation (ES) at acupoint Zusanli (ST36) can inhibit the bone loss caused by Staphylococcus aureus (SA) infection and its mechanism in a model of SA osteomyelitis.Methods:Twelve male C57 BL/6 mice aged 10 to 12 weeks were randomly divided into 2 even groups ( n=6) for SA infection + ES or SA infection only. After ES at ST36 was conducted for 4 weeks in the model of SA osteomyelitis, samples were harvested from the femora and tibiae. Micro-CT reconstruction was performed to detect trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), connectivity density (Conn.Dn) to analyze changes in bone mass. Leptin receptor (LEPR) staining was performed to detect osteoblasts. Tartrate resistant acid phosphatase (TRAP) staining was used to detect the changes in osteoclasts. The changes in plasma inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Results:Micro-CT results showed that the BV/TV, Tb.N, Tb.Th, and Conn.Dn in the cancellous bone in the target areas in the SA + ES group were all higher than those in the SA group, LEPR immunofluorescence results indicated that the number of osteogenic precursor cells in the ES group was larger than that in the SA group, and serum ELISA indicated a decrease in inflammatory factors in the blood in the SA+ES group compared with the SA group. There were significant differences in the comparisons above ( P<0.05). There was no significant difference in the number of osteoclasts on the surface of trabecular bone between the 2 groups in TRAP staining. Conclusion:ES may slow down infectious bone destruction by inhibiting the inflammatory response induced by SA infection and by inducing aggregation and differentiation of mesenchymal stem cells into trabecular bone.
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Osteochondral lesions of the talus (OLT) frequently manifest following ankle joint trauma, causing ankle pain, swelling and impaired mobility, thereby significantly impeding daily activities of the patients. Presently, clinical treatment approaches encompass both conservative management and surgical intervention. Conservative management endeavors to alleviate symptoms, while patients experiencing persistent symptoms resort to surgical intervention. Commonly employed surgical treatments encompass bone marrow stimulation, autologous osteochondral transplantation, and allogeneic osteochondral transplantation. Bone marrow stimulation is employed as a therapeutic approach for the management of smaller OLT, demonstrating favorable short-term effectiveness; however, the long-term prognosis remains uncertain. Autologous osteochondral transplantation is a viable option for larger OLT lesions, albeit it carries the potential of complications at the donor site. Conversely, allogenic osteochondral transplantation exhibits a diminished success rate. In recent times, the utilization of cell transplantation techniques has garnered escalating interest in the treatment of OLT due to their capacity to regenerate cartilage resembling hyaline and their diverse range of cellular origins. The authors reviewed the progress of cell transplantation in the treatment of OLT, providing a reference for the clinical treatment.
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Objective:To investigate and compare the regulatory effects of umbilical cord mesenchymal stem cells (MSC) and their conditioned medium (MSC-CM) on gut microbiota of septic mice.Methods:Twenty-eight six-to-eight-week-old female C57BL/6J mice were randomly divided into sham operation group (Sham group), sepsis model group (CLP group), sepsis+MSC treatment group (CLP+MSC group) and sepsis+MSC-CM treatment group (CLP+MSC-CM group), with seven mice in each group. The septic mouse model was established by cecal ligation and puncture (CLP). In Sham group, CLP were not performed, and other operations were the same as CLP group. Mice in the CLP+MSC group and CLP+MSC-CM group received 0.2 mL 1×10 6 MSC or 0.2 mL concentrated MSC-CM via intraperitoneal injection 6 hours after CLP, respectively. Sham group and CLP group were given 0.2 mL sterile phosphate buffer saline (PBS) via intraperitoneal injection. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining and colon length. Levels of inflammatory factors in serum were detected by enzyme-linked immunosorbent assay (ELISA). Phenotype of peritoneal macrophages was analyzed by flow cytometry, and the gut microbiota was analyzed via 16S rRNA sequencing. Results:Compared with Sham group, significant inflammatory injury in lung and colon was observed, and shorter colon was detected in CLP group (cm: 6.00±0.26 vs. 7.11±0.09), the level of inflammatory cytokine interleukin-1β (IL-1β) in serum was significantly increased (ng/L: 432.70±17.68 vs. 353.70±17.01), the proportion of F4/80 + peritoneal macrophages was increased [(68.25±3.41)% vs. (50.84±4.98)%], while the ratio of F4/80 +CD206 + anti-inflammatory peritoneal macrophages was decreased [(45.25±6.75)% vs. (66.66±3.36)%]. The α diversity sobs index of gut microbiota was downregulated significantly (118.50±23.25 vs. 255.70±6.87), the structure of species composition was altered, and the relative abundance of functional gut microbiota related to transcription, secondary metabolites biosynthesis, transport and catabolism, carbohydrate transport and metabolism, and signal transduction were decreased significantly in CLP group (all P < 0.05). Compared with CLP group, upon MSC or MSC-CM treatment, the pathological injury in lung and colon was alleviated to varying extent, the length of colon was increased (cm: 6.53±0.27, 6.87±0.18 vs. 6.00±0.26), the level of IL-1β in serum was downregulated (ng/L: 382.10±16.93, 343.20±23.61 vs. 432.70±17.68), the ratio of F4/80 + peritoneal macrophages was decreased [(47.65±3.93)%, (48.68±2.51)% vs. (68.25±3.41)%], the ratio of F4/80 +CD206 + anti-inflammatory peritoneal macrophages was increased [(52.73±5.02)%, (66.38±4.73)% vs. (45.25±6.75)%], and the α diversity sobs index of gut microbiota was increased (182.50±16.35, 214.00±31.18 vs. 118.50±23.25), and the effects of MSC-CM were more significant (all P < 0.05). At the same time, species composition of gut microbiota was rebuilt, and a tendency of increase in relative abundance of functional gut microbiota was observed upon MSC and MSC-CM treatment. Conclusion:Both MSC and MSC-CM could alleviate inflammatory injury in tissues, and showed regulatory effects on gut microbiota in septic mouse model, moreover, MSC-CM exhibited superior advantages over MSC.
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Bronchopulmonary dysplasia(BPD) is a chronic lung disease in the premature infants, which is an important cause of poor prognosis in the premature infants.The pathogenesis of BPD involves a variety of prenatal and postnatal mechanisms affecting the development of immature lungs.The combined effect of BPD alters lung morphogenesis, disrupts capillary gas exchange in the alveoli, and leads to pathological and clinical features of BPD.The current clinical methods used to treat BPD are still difficult to improve its prognosis.Mesenchymal stem/stromal cell(MSC) is a promising and innovative therapy for the treatment of a wide range of diseases due to the ease of extraction, low immunogenicity, anti-inflammatory properties and regenerative ability.In recent years, many experimental and clinical studies have found and proved that mesenchymal stem cell transplantation has a certain effect on BPD, so MSC may become the promising treatment for BPD in the future.However, the possibility that MSC may promote tumor growth, the presence of heterogeneous cell populations resulting in different efficacy, and ethical issues regarding the use of this treatment in humans make it a number of therapeutic challenges.This article reviews the mechanism of action and treatment of MSC in BPD, as well as the research progress in the treatment of BPD with MSC.
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Objective To investigate the effects of glucose and serum deprivation under hypoxia(GSDH)treatment on oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells (BMSCs), so to provide an experimental support for improving the therapeutic efficacy of BMSCs. Methods The cell injury model was established by hypoxia (1% O
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Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.
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Mice , Animals , Cell Line, Tumor , Cell Proliferation , Mice, Nude , Epithelial-Mesenchymal Transition , Thyroid Neoplasms/pathology , Extracellular Vesicles/pathology , Mesenchymal Stem Cells , Transcription Factors, TFIII/metabolism , Neoplastic Stem Cells/pathologyABSTRACT
【Objective】 To investigate the effects of miR-126-3p targeting chemokine receptor 1 (CCR1) in exosomes derived from bone marrow mesenchymal stem cells (BMSC) on the proliferation, migration, and invasion of lung cancer cells. 【Methods】 BMSC cells were cultured; exosomes were extracted and identified by the exosomal marker proteins CD63 and TSG101. After exosome culture of A549 cells for different durations (0, 24, 48, and 72 h), cell survival rate was detected by CCK-8, mRNA levels of miR-126-3p and CCR1 were detected by qRT-PCR, and cell migration and invasion abilities were detected by Transwell assay. The relative expressions of CCR1, epithelial cadherin (E-cad), neural cadherin (N-cadherin), and Vimentin were detected by Western blotting. 【Results】 Exosomes had round or oval cup-shaped structures with bright edges and dark middle, with a particle size distribution of about 152 nm, expressing CD63 and TSG101 proteins. The expression of miR-126-3p in exosomes was higher than that in A549 cells. The expression of miR-126-3p was low in A549 cells and that of CCR1 mRNA was high. However, after co-culture with exosomes, the expression of miR-126-3p in A549 cells was increased, while the expression of CCR1 was decreased. A549 cells were cocultured with exosomes for 0, 24, 48, and 72 h. The survival rate, migration and invasion abilities, CCR1 gene and protein expression levels, and N-cad and Vimentin protein expression levels of A549 cells decreased gradually with the extension of culture time. The level of miR-126-3p and the expression of E-cad protein increased gradually with the extension of culture time. 【Conclusion】 The co-culture of exosomes derived from bone marrow mesenchymal stem cells with A549 cells can increase the expression level of miR-126-3p, and miR-126-3p can reduce the proliferation, migration, and invasion of A549 cells by targeting the inhibition of CCR1 expression.
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@#The aim of the present study was to investigate the effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the polarization of M1/M2 microglia/macrophages in rats with acute cerebral ischemia.Ultrahigh-speed centrifugation was employed to isolate and identify exosomes; a middle cerebral artery occlusion (MCAO) model was prepared in rats using the intraluminal filament technique; Longa scoring and corner tests were used to evaluate the neurological function of rats; 2, 3, 5-triphenyltetrazole chloride (TTC) staining was used to assess the infarct volume in rat brains; immunofluorescence double-labeling of CD16/32/Iba1 and CD206/Iba1 was performed to detect M1/M2 phenotypes of microglia/macrophages; RT-qPCR was employed to measure the mRNA expression of CD86, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), arginase-1 (Arg-1), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in the ischemic penumbra of rat brains.The experimental results showed that BMSC-Exos reduced the number of CD16/32+/Iba1+ positive cells in the ischemic penumbra (P < 0.01) while increasing the number of CD206+/Iba1+positive cells (P < 0.01), and decreased the mRNA expression of iNOS, CD86, and TNF-α, while increasing the mRNA expression of Arg-1, TGF-β, and IL-10 (P < 0.05 or P < 0.01).This research suggests that BMSC-Exos can regulate M1/M2 polarization of microglia/macrophages in rats with acute cerebral ischemia, alleviate neuroinflammation, and improve ischemic brain injury.
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ObjectiveTo investigate the therapeutic effect of the frozen and fresh preparations of human umbilical cord mesenchymal stem cells （hUC-MSC） on a rat model of liver cirrhosis after transplantation via the portal vein or the caudal vein. MethodsA total of 70 specific pathogen-free healthy male Sprague-Dawley rats were randomly divided into normal group （13 rats fed with ordinary tap water and rat food） and liver cirrhosis model group （57 rats given subcutaneous multi-point injection of mixed carbon tetrachloride/olive oil solution）. At week 8， the growth of rats was observed for both groups， and 3 rats were selected from each group for histopathological examination to confirm the formation of liver cirrhosis. A total of 50 rats were selected from the liver cirrhosis model and were divided into model group， portal vein group+fresh cell preparation group， portal vein+frozen cell preparation group， caudal vein+fresh cell preparation group， and caudal vein+frozen cell preparation group using a random number table， with 10 rats in each group. Fresh or frozen hUC-MSC were transplanted via the portal vein or the caudal vein， and after 4 weeks of administration， the different groups were compared in terms of the changes in liver function parameters and liver fibrosis degree. Continuous data were expressed as mean±standard deviation， and the independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsAt week 8 of modeling， the model group showed the formation of pseudolobules of different sizes in the liver and met the diagnostic criteria for liver cirrhosis， with significant increases in the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBil）， and alkaline phosphatase （ALP） compared with the normal group （all P<0.001）， suggesting that the rat model of liver cirrhosis was established successfully. There were significant differences in the levels of ALT， AST， TBil， and ALP between the five groups （F=232.00， 177.10， 112.30， 121.70， all P<0.001）. Further comparison between two groups showed that the model group had significantly higher levels of ALT， AST， TBil， and ALP than the normal group （all P<0.01）， and the portal vein group+fresh cell preparation group， the portal vein+frozen cell preparation group， the caudal vein+fresh cell preparation group， and the caudal vein+frozen cell preparation group had significantly lower levels of ALT， AST， TBil， and ALP than the model group （all P<0.01）. ConclusionThere are significant improvements in liver function and liver fibrosis degree in a rat model of liver cirrhosis at week 4 after the transplantation of hUC-MSC， and frozen or fresh cell preparation and different transplantation approaches have no significant influence on treatment outcome.
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@#The ultimate treatment goal of periodontitis is the structural and functional regeneration of periodontium. However, existing methods for periodontal regeneration have difficulties in regenerating the hierarchical structure. Therefore, stem cell-based tissue engineering has attracted more and more attention for its advantages of self-renewal and multi-lineage differentiation potential. This review summarized the progress of research on periodontal tissue regeneration by combined biomaterials of dental-derived stem cells. It is pointed out that the application of autologous stem cell transplantation is limited by the donor source, and the subsequent research should focus on the development of multi-phase scaffold materials and the attempt to establish a stem cell bank.
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@#Both Wnt/β-catenin signaling pathway and NF-κB signaling pathway are highly conservative pathways that regulate a variety of biological processes, and their cross-regulation have attracted attention in many biological and medical research fields. In this review, we summarize the cross-regulation between Wnt/β-catenin signaling pathway and NF-κB signaling pathway and discuss their involvement in the multi-directional differentiation of mesenchymal stem cells.
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In recent years, organ transplantation has developed rapidly in China, whereas the proportion of supply and demand of organs for donation is severely unbalanced. To resolve the shortage of donor livers, repairing extended criteria donor liver and improving the quality of donor liver are critical research directions. Mesenchymal stem cell (MSC) is a category of stem cells with self-renewal and differentiation potential, which possess the functions of immunomodulation and tissue repair. The derivatives of MSC have the advantages of low immunogenicity and high biocompatibility, which have been widely applied in the treatment of multiple diseases. In this article, research progress on the role of MSC, exosomes and extracellular vesicles in alleviating liver steatosis, repairing ischemia-reperfusion injury and promoting the regeneration of small-for-size liver allograft was reviewed, and the feasibility and safety of MSC and the derivatives in repairing donor liver were summarized, aiming provide novel ideas for repairing marginal donor liver and enhancing the quality of liver allograft.
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Objective To evaluate the effect of mesenchymal stem cell (MSC) coated-islets on instant blood-mediated inflammatory reaction (IBMIR) after islet transplantation. Methods MSC labeled with tracer and human islets were placed into an ultra-low adsorption cell culture dish, shaken and mixed twice at an interval of 0.5 h, and then incubated at 37 ℃ and 5% CO2 for 24 h to obtain MSC-coated islets. The coating effect of MSC and in vitro function of the islets were assessed. A blood circulation tube-shaped model was established in vitro. In the blank control group, 0.2 mL of islet culture solution was added. In the islet group, 800 islet equivalent quantity (IEQ) of uncoated islets were supplemented. In the MSC-coated islets group, 800 IEQ of MSC-coated islets were added, and circulated for 60 min at 37 ℃. A portion of 0.5 mL blood sample was taken for routine blood test at 0, 30 and 60 min, respectively. After 60 min circulation, the blood sample was filtered with a 70 μm filter to collect plasma, blood clots and islets. Blood clots and islets were subject to hematoxylin-eosin (HE) staining and immunohistochemical staining. Morphological changes and the aggregation of CD11b-positive cells surrounding the islets were observed. The contents of plasma thrombin-antithrombin complex (TAT), tissue factor (TF), C3a, C5b-9, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and IL-8 were determined by enzyme-linked immune absorbent assay. Results After 24 h co-incubation, the islets were coated by MSC, with a coating degree of approximately 80%. In the islet and MSC-coated islet group, a large quantity of neutrophils and monocytes were observed surrounding the blood clots and islets, and the quantity of CD11b-positive cells in the MSC-coated islet group was less compared with that in the islet group. After co-incubation with the whole blood for 0, 30 and 60 min, the quantity of platelets, neutrophils and monocytes was declined in the MSC-coated and islet groups, and gradually decreased over time. Compared with the blank control group, the quantity of platelets, monocytes and neutrophils was lower, whereas the TF content was higher in the MSC-coated islet group. Compared with the islet group, the quantity of platelets, monocytes and neutrophils was higher, whereas the TAT and TF contents were less in the MSC-coated islet group, the differences were statistically significant (all P < 0.05). Compared with the blank control group, the expression levels of C3a, C5b-9, IL-6, TNF-α and IL-8 were up-regulated in the MSC-coated islet group. Compared with the islet group, the expression levels of C3a, C5b-9, IL-1β, IL-6, TNF-α, IL-8 and MCP-1 were down-regulated in the MSC-coated islet group, and the differences were statistically significant (all P < 0.05). Conclusions MSC-coated islets may reduce the exposure of islet TF in the blood and prevent the incidence of IBMIR during the coagulation response stage, thereby mitigating the injury and loss of islet allograft in the early stage of islet transplantation.