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Despite significant progress in the field of medicine, cardiovascular illnesses continue to be the primary cause of mortality on a global scale. The increasing prevalence of cardiovascular illnesses necessitates the exploration of novel and potential therapeutic strategies to address the escalating risk associated with CVDs. Stem cell therapy has emerged as the central focus of regenerative cardiovascular medicine, surpassing all other treatments and therapies. Multiple clinical trials and studies have demonstrated that stem cell therapy, particularly mesenchymal stem cells, is the most appealing approach for treating cardiac disorders due to their significant therapeutic potential. Recent research have shown that mesenchymal stem cells have a positive impact on several cardiac muscle diseases, such as heart failure, problems with blood vessel lining, damage caused by lack of blood flow, and high blood pressure in the lungs. This study specifically examines the potential, preconditioning techniques, methods of administration, and mechanisms of mesenchymal stem cell (MSC) therapy for the treatment of cardiovascular diseases (CVDs).
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BACKGROUND:Medical hydrogels are new functional polymer materials with three-dimensional structural networks and excellent biocompatibility,which have been widely studied in the field of tissue engineering and drug carriers,but the research on the combination of medical hydrogels and Chinese medicine for the treatment of diseases based on tissue engineering is still in the early exploration stage.Therefore,through the analysis of the mechanism of the role of medical hydrogels,the integration of medical hydrogels and Chinese medicine in the research of the joint application of the article,can better provide ideas for scientific researchers,and the joint application of Chinese medicine and medical hydrogels is of great significance. OBJECTIVE:To explore the strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment based on tissue engineering research. METHODS:PubMed and CNKI were used to retrieve articles about the application of Chinese medicine combined with medical hydrogel in tissue engineering from January 2010 to November 2022,with the Chinese and English search terms"hydrogel,traditional Chinese medicine,drug carrier,tissue engineering".After the initial screening of all articles according to the inclusion and exclusion criteria,the 61 articles with high relevance were retained for review. RESULTS AND CONCLUSION:(1)Although the application of Chinese medicine combined with medical hydrogel is involved in intra-articular,intra-tissue organ,soft tissue wounds,tissue engineering,etc.,except for the clinical application of Chinese medicine combined with hydrogel dressing for soft tissue injury,other aspects are still in the experimental stage.(2)The development of Chinese medicine combined with medical hydrogel has great potential and development prospects,but there is a certain difficulty in the manufacture of the gel with high-performance requirements,and it is difficult to master the physical and chemical properties precisely.(3)At present,the comprehensive view of injectable hydrogel with the characteristics of easy to use,its joint use of Chinese medicine can be extended to a wider range,can be used for joint,organ,tissue engineering-related disease treatment.Smart hydrogel has high sensitivity and reversible transformation can also meet the use of the special environment.During the combined use of Chinese medicine,it also needs to understand the mechanism of action of Chinese medicine components.(4)The strategy of combining Chinese medicine with medical hydrogels for disease treatment should start with matching the therapeutic effects of Chinese medicine on organs,tissues and cells combined with appropriate types of medical hydrogels to make up for the shortcomings of traditional Chinese medicine delivery methods and frequent drug delivery.In tissue engineering,hydrogels can be loaded with stem cells after Chinese medicine intervention,or with both Chinese medicine and stem cells for disease treatment.(5)In future research of combined Chinese medicine and medical hydrogel application,we also need to consider:we should ensure that the biological properties of medical hydrogel can be quantified,and grasp the characteristics of hydrogel with different manufacturing processes of different materials to produce the required medical hydrogel that meets the application conditions.In Chinese medicine,we need to comprehensively understand and analyze the therapeutic effects and application mechanisms of known Chinese medicine monomer and Chinese medicine compound extracts,so as to achieve a more perfect combination between Chinese medicine and medical hydrogel under a more clear mechanism.With the continuous improvement of medical science and technology innovation,the medical hydrogel can be innovatively combined with other traditional treatment methods of Chinese medicine,such as acupuncture,massage,cupping and so on,to be used from multiple angles.
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BACKGROUND:In cartilage degeneration in osteoarthritis,cytokines and signaling pathways that target chondrocytes play an important role. OBJECTIVE:To review the latest research progress of osteoarthritis related cytokines and signaling pathways in recent years,such as the mechanism of action and treatment modalities,in order to provide a basis for future exploration of new therapeutic targets and modalities. METHODS:Literature search was conducted on CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases.Chinese search terms were"osteoarthritis,cytokines,signal pathway,chondrocyte,inflammation,treatment".Finally,60 papers were included for review. RESULTS AND CONCLUSION:(1)In current studies,it is believed that the specific mechanism of osteoarthritis is not clear,and a large number of studies have shown that osteoarthritis is strongly associated with cytokines and signaling pathways,which is a complex process of action.Relevant studies taking cytokines and signaling pathways as therapeutic breakthroughs are also the current hot spot.(2)The receptor antagonists of pro-inflammatory factors such as interleukin 1 are not effective in the treatment of osteoarthritis,and more studies turn to gene therapy.(3)The therapeutic methods of transforming growth factor β,recombinant factors of Wnt signaling pathway,gene therapy and mesenchymal stem cells have obtained positive research results.However,basic and clinical studies on safety and efficacy are likely to be conducted in future studies.(4)At present,relevant therapeutic methods such as platelet-rich plasma have been widely used in clinical practice,while recombinant factor,gene therapy and mesenchymal stem cell therapy are all in the research stage,among which mesenchymal stem cell therapy and gene therapy are expected to make breakthroughs in the field of cartilage repair and regeneration,and are worthy of expectation in the future.However,more clinical and basic studies are needed to verify its effectiveness and safety,explore its mechanism of action and scope of application,and set standards for its clinical use.
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BACKGROUND:Platelet-rich plasma has been shown to enhance the viability and the pro-angiogenesis capacity of mesenchymal stem cells.Extracellular vesicles are one of the key mediators for mesenchymal stem cells to exert their effects,but currently,it is unclear whether platelet-rich plasma affects the functions of extracellular vesicles. OBJECTIVE:To investigate the effects of platelet-rich plasma on the function of extracellular vesicles from bone marrow mesenchymal stem cells,verify whether platelet-rich plasma can be used as an adjuvant to enhance the healing effects of bone marrow mesenchymal stem cells on repairing the peripheral nerve injury. METHODS:For in vitro study,bone marrow mesenchymal stem cells were cultured under normal conditions and with 1%platelet-rich plasma.The ultracentrifugation was used to extract the extracellular vesicles produced by bone marrow mesenchymal stem cells cultured under normal conditions(EVs-nor)or the condition supplemented with 1%platelet-rich plasma(EVs-prp).Extracellular vesicles were used to incubate with Schwann cells.The EdU assay,western blot assay,qPCR and light microscopy photography were performed to examine the effects of EVs-nor and EVs-prp on Schwann cell reprogramming,which was characterized by cell proliferation,c-Jun expression,reprogramming-associated gene expression and cell morphology.For in vivo study,the model of sciatic nerve injury in rats was established.Bone marrow mesenchymal stem cells were grafted with or without 1%platelet-rich plasma into the injured rat sciatic nerve using a chitin nerve conduit.Eight weeks after the surgery,the recovery was assessed by histological and functional indexes,including regenerated nerve fiber density,gastrocnemius wet weight ratio and sciatic function index. RESULTS AND CONCLUSION:(1)Compared with EVs-nor,EVs-prp was stronger in promoting Schwann cell proliferation.The gene expressions of c-Jun and GDNF were significantly upregulated in EVs-prp treated Schwann cells.The morphology of Schwann cells was significantly longer in EVs-prp group than that in EVs-nor group,indicating that EVs-prp had a stronger ability to stimulate Schwann cell reprogramming than EVs-nor.(2)Sciatic nerve injury animal experiment results revealed that grafting mesenchymal stem cells along with platelet-rich plasma into the injured sciatic nerve showed the best recovery compared with grafting mesenchymal stem cells or platelet-rich plasma alone,demonstrated by the significantly improved density of nerve fibers,gastrocnemius wet weight ratio,and sciatic function index.(3)These results suggested that platelet-rich plasma improved the function of bone marrow mesenchymal stem cell-derived extracellular vesicles and could be served as a practical and feasible preparation to synergize with bone marrow mesenchymal stem cells to improve peripheral nerve repair.
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BACKGROUND:Transplantation of stem cell-derived islet β cells has been considered effective for the treatment of type 1 diabetes.Human umbilical cord mesenchymal stem cell is an ideal cellular source,but with a low differentiation efficiency to islet β cells. OBJECTIVE:To explore the possibility of human umbilical cord mesenchymal stem cells modified by MAFA and PDX1 to differentiate into insulin-producing cells. METHODS:MAFA-PDX1 lentivirus expression vectors were constructed.The efficiency and potentiality of human umbilical cord mesenchymal stem cells differentiated into insulin-producing cells with three methods were compared by cell morphology,RT-qPCR,and dithizone staining[protocol A:Simple lentivirus group;protocol B:Drug(nicotinamide β-mercaptoethanol)induction followed by lentivirus group;protocol C:lentivirus and drug induction group]. RESULTS AND CONCLUSION:(1)Morphological change of cells:Cell morphology was all altered after the induction of three protocols.At day 11,human umbilical cord mesenchymal stem cells induced by protocol B showed the most cell clusters among the three protocols,appearing aggregated islet-like cell clusters.(2)Islet-related gene expression detected by RT-qPCR:Horizontal comparison of the three protocols at the same induction time point showed that the expression levels of MAFA and PDX1 genes were the highest in protocol C on day 5 of induction,and those in protocol B were the highest on day 11 of induction.Human umbilical cord mesenchymal stem cells induced by protocol B had the greatest expression of GCG gene at day 5,INS and GLUT2 genes at day 11.(3)Dithizone staining to identify zinc ions:parts of the post-induced cells were stained brownish red by dithizone on day 11.The partial small island cells were stained brownish red with a darker color(positive expression)in protocol B.(4)It is concluded that the overexpression of MAFA and PDX1 can promote the differentiation of human umbilical cord mesenchymal stem cells into insulin-producing cells.The combination of MAFA-PDX1 gene modification and drug induction is superior to the single gene modification.
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BACKGROUND:At present,many drugs used in the treatment of polycystic ovary syndrome are super-designated drugs,and the treatment of patients with polycystic ovary syndrome still faces great challenges.Studies have shown that human umbilical cord mesenchymal stem cells can repair ovarian function,but few studies have reported their therapeutic effect on polycystic ovary syndrome. OBJECTIVE:To investigate the therapeutic effect of human umbilical cord mesenchymal stem cells on polycystic ovary syndrome,and to preliminarily explore the correlation between mitochondrial autophagy and the improvement of polycystic ovary syndrome by human umbilical cord mesenchymal stem cells. METHODS:Polycystic ovary syndrome mouse model was established by subcutaneous injection of dehydroepiandrosterone for 20 days into C57BL/6J mice.Human umbilical cord mesenchymal stem cells(2×106)were injected through the caudal vein.After treatment,vaginal secretions were collected for 10 consecutive days to detect the estrus cycle of mice.At 2 weeks after treatment,the levels of sex hormones in the peripheral blood of mice,including luteinizing hormone and follicle-stimulating hormone,were detected by ELISA.Hematoxylin-eosin staining was used to evaluate ovarian histopathology.Finally,mitochondrial autophagy in ovaries was observed by transmission electron microscopy. RESULTS AND CONCLUSION:(1)After human umbilical cord mesenchymal stem cell therapy,follicles at different stages(primitive follicles,primary follicles,and secondary follicles)appeared in the ovary of polycystic ovary syndrome mice,and luteal tissue could be seen,indicating that ovulation function of mice was effectively improved.(2)Polycystic ovary syndrome mice treated with human umbilical cord mesenchymal stem cells had sex hormone levels.(3)Untreated polycystic ovary syndrome mice were found to be in the estrous stage for a long time,lacking estrous interphase and estrous phase,but after human umbilical cord mesenchymal stem cell therapy,the estrous cycle returned to a normal level.(4)After treatment with human umbilical cord mesenchymal stem cells,the mitochondrial autophagy of polycystic ovary syndrome mice was significantly reduced.(5)The results show that human umbilical cord mesenchymal stem cells can effectively improve the symptoms of endocrine disorders and promote ovulation in polycystic ovary syndrome mice,which may be related to the inhibition of mitochondrial autophagy.
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BACKGROUND:The aging of mesenchymal stem cells is one of the main causes of aging-related diseases,and seriously affects its clinical application.Traditional Chinese medicine has a good anti-aging effect,and it can inhibit the aging of mesenchymal stem cells to promote its application in tissue engineering and prevent and treat aging-related diseases. OBJECTIVE:To review the effect and mechanism of traditional Chinese medicine on inhibiting the aging of mesenchymal stem cells. METHODS:We searched CNKI and PubMed for the literature on inhibiting mesenchymal stem cell aging with traditional Chinese medicine from 2012 to 2022.The keywords were"traditional Chinese medicine,mesenchymal stem cells(MSCs),aging"in Chinese and English,respectively.Finally,92 articles were included for further review. RESULTS AND CONCLUSION:(1)We summarized five main mechanisms of the aging of mesenchymal stem cells:DNA damage,telomere shortening,oxidative stress,autophagy disorder and mitochondrial dysfunction.(2)This paper reviewed the phenotypic characteristics of senescent mesenchymal stem cells,including increases in cell volume,decreases in proliferation and multi-directional differentiation,increases in β-galactosidase activity,and activation of p21 and p16 pathways,and so on.(3)We summarized the main mechanisms of Chinese medicine inhibiting the senescence of mesenchymal stem cells at present,including inhibiting the activation of the Wnt pathway,inhibiting the production of mitochondrial reactive oxygen species,promoting the silencing of information regulator factor 2 homolog 1,phosphatidylinositol 3-kinase/protein kinase B,adenosine 5'-monophosphate-activated protein kinase and nuclear factor E2 related factor 2 pathway activation,and promoting the expression of telomerase reverse transcriptase.(4)At present,bone marrow mesenchymal stem cells are the most widely studied in the research of traditional Chinese medicine to inhibit the aging of bone marrow mesenchymal stem cells,and the effect is better.(5)Zuogui Wan,Bushen Tiaogan Formula,resveratrol,Astragalus membranaceus and other traditional Chinese medicines can prevent and treat osteoporosis by promoting the proliferation and osteogenic differentiation of aging mesenchymal stem cells.However,the mechanism of Chinese medicine in improving the paracrine function of mesenchymal stem cells and preventing other aging-related diseases by inhibiting the aging of mesenchymal stem cells needs to be further explored.
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OBJECTIVE:To evaluate the efficacy of exosomes derived from mesenchymal stem cells on animal models of acute liver failure. METHODS:PubMed,Web of Science,Embase,The Cochrane Library,CBM,CNKI,WanFang,and VIP databases were retrieved from inception to January 16,2023.A series of animal experiments on the treatment of acute liver failure animal models by exosomes derived from mesenchymal stem cells were collected.Two evaluators screened the literature and extracted the data independently.The bias risk was evaluated by the SYRCLE tool.The extracted data were analyzed by Revmen 5.4.1 software and Stata 17.0 software. RESULTS:A total of 241 articles were retrieved and 9 animal experiments were included,with 219 animals:110 animals in the model group and 109 animals in the exosome group.The results showed that the survival rate of animals in the exosome group improved significantly[RR=9.34,95%CI(3.91,22.29),P<0.001],the levels of serum alanine transaminase[SMD=-5.31,95%CI(-7.43,-3.19),P<0.001]and aspartate aminotransferase[SMD=-4.47,95%CI(-5.85,-3.10),P<0.001]were reduced obviously.The expressions of interleukin-1β[SMD=-11.54,95%CI(-18.12,-4.95),P=0.000 6],interleukin-6[SMD=-5.75,95%CI(-8.08,-3.41),P<0.001]and tumor necrosis factor-α[SMD=-4.46,95%CI(-6.83,-2.09),P=0.000 2],were suppressed obviously. CONCLUSION:Exosomes derived from mesenchymal stem cells effectively inhibit the inflammatory response,ameliorate liver function of animals with acute liver failure,and improve their survival rate.The results of subgroup analysis showed that the shorter survival time of animals(≤24 hours),the lower dose of transplanted exosomes(<1 mg/kg)and the source of exosomes(adipose-derived mesenchymal stem cells)may affect the efficacy of the exosomes derived from mesenchymal stem cells in the animal model of acute liver failure.This conclusion and its clinical transformation still need to be confirmed by randomized controlled studies with large sample sizes and high quality.
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BACKGROUND:HLA haploid allogeneic hematopoietic stem cell transplantation provides a chance of survival for patients with high-risk hematologic malignancies.In recent years,the research on the transplantation mode and graft selection of haploidentical transplantation is still ongoing.At present,the mixed transplantation model of non-extracorporeal T-cell removal bone marrow and peripheral blood stem cells established by the Hematology Research Center of Peking University is gradually becoming popular in China,but this model requires the collection of donor bone marrow fluid,which increases the pain and risk of the donor. OBJECTIVE:To explore the curative effect of infusion of umbilical cord mesenchymal stem cells replacing donor bone marrow cells in haploidentical peripheral blood hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:Fifty hematological malignancies patients who underwent haploidentical hematopoietic stem cell transplantation from January 2019 to May 2022 were selected and randomly assigned to two study groups at a ratio of 2:3.Among them,19 patients received umbilical cord mesenchymal stem cell combined with peripheral blood stem cell transplantation,and 31 patients were treated with bone marrow cells combined with peripheral blood stem cells.The study was approved by the Ethics Committee of Henan Provincial People's Hospital.The recipients of umbilical cord mesenchymal stem cells were first transfused with third-party umbilical cord mesenchymal stem cells(1×106/kg)on the day of transplantation,followed by peripheral blood hematopoietic stem cells 6 hours later.In the bone marrow group,donor bone marrow cells were transfused +1 day after transplantation and peripheral blood stem cells were transfused +2 days after transplantation.After transplantation,rabbit anti-human thymocyte immunoglobulin,cyclosporine A,mycophenolate mofetil,and a short-course methotrexate were used for graft-versus-host disease prophylaxis for all recipients. RESULTS AND CONCLUSION:No adverse events occurred during the reinfusion of umbilical cord mesenchymal stem cells.There were no significant differences between the mesenchymal stem cell group and the bone marrow group in the engraftment rate[100%(19/19)vs.96.8%(30/31),P>0.05],median duration for neutrophil engraftment(14 days vs.15 days,P>0.05)and median duration for platelet engraftment(20 days vs.19 days,P>0.05).The incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease in the mesenchymal stem cell group was significantly lower than in the bone marrow group[21.1%(4/19)vs.58.1%(18/31),P = 0.01].There were no significant differences between the two groups in the incidence of chronic graft-versus-host disease[21.1%(4/19)vs.25.8%(8/31),P>0.05],the relapse rates[15.8%(3/19)vs.16.1%(5/31),P>0.05]and the incidence of early cytomegalovirus viremia[42.1%(8/19)vs.35.5%(11/31),P>0.05],and the 2-year overall survival rate[68.4%(10/19)vs.70.9%(16/31),P>0.05].It is indicated that umbilical cord mesenchymal stem cells replace donor bone marrow cells in haploidentical peripheral blood stem cell transplantation for malignant hematological diseases,which reduced the incidence of acute graft-versus-host disease after transplantation,did not increase the incidence of chronic graft-versus-host disease,recurrence rate and early cytomegalovirus viremia,and reduced the pain and risk of donor pulp extraction.
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BACKGROUND:Currently,a variety of mesenchymal stem cells have been confirmed to have the effect of promoting wound repair,but there is still a lack of relevant research on whether placenta-derived mesenchymal stem cells can promote acute skin wound healing. OBJECTIVE:To investigate the effect of placenta-derived mesenchymal stem cell transplantation on the healing of acute skin wound in rats. METHODS:Twenty SD rats were divided into PBS group and stem cell group by the random number table method,with 10 rats in each group.All rats were selected to establish a full-thickness skin defect model.In the PBS group and stem cell group,PBS buffer and placenta-derived mesenchymal stem cells were immediately injected on the wound surface and wound margin immediately and on day 8 after modeling.The wound healing was observed immediately and on days 2,4,6,8,10,12,and 14 after modeling.The skin tissue of the wound surface was taken on day 14 and treated with hematoxylin-eosin staining,Masson staining,immunohistochemical staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1)The wound surface of the rats in each group decreased with the prolongation of treatment time.The wound healing rate and wound epithelization rate of the stem cell group at 14 days were higher than those of the PBS group(P<0.01),and the wound contracture rate was lower than that of the PBS group(P<0.01).(2)The results of hematoxylin-eosin staining showed that the skin wound healing of the stem cell group was better than that of the PBS group;the degree of wound epithelization was higher,and the morphology of collagen fibers was close to that of normal skin.(3)Masson staining results showed that compared with the PBS group,collagen fibers in the skin wound tissue of the stem cell group were significantly increased and thicker,and the content of collagen fibers in the new tissue was significantly higher than that of the PBS group(P<0.01).(4)Immunohistochemical staining showed that the number of new capillaries in the stem cell group was higher than that in the PBS group(P<0.01),while the expressions of tumor necrosis factor-α and interleukin-6 were lower than those in the PBS group(P<0.01).(5)Immunofluorescence staining showed that the number of M2 macrophages in the new wounds of the stem cell group was higher than that of the PBS group(P<0.01),while the number of M1 macrophages was less than that in the PBS group(P<0.01).These findings indicate that placenta-derived mesenchymal stem cells can accelerate skin wound healing,promote wound epithelization,and reduce wound contracture,which may be related to the promotion of capillary angiogenesis,regulation of collagen fiber production,inhibition of inflammation,and regulation of macrophage polarization to M2 type.
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BACKGROUND:Mouse osteogenic potential is regulated by the JAK-STAT signaling pathway,and interleukin-9 can regulate multiple cellular functions through the JAK-STAT pathway,which has the potential to be a novel cytokine that regulates osteogenic potential. OBJECTIVE:To investigate the effect of interleukin-9 deficiency on osteogenic potential in mice METHODS:The femurs collected from 2-month-old wild-type and interleukin-9 knockout mice were subjected to Micro-CT scanning to analyze the changes in bone mass.Then,hematoxylin-eosin staining,Masson staining,and immunohistochemical staining of type Ⅰ collagen were performed on the slices of the femurs of mice.Bone marrow cells from 2-month-old wild-type and interleukin-9 knockout mice were extracted for colony-forming assay and detection of osteogenic gene expression in bone marrow mesenchymal stem cells.To further verify whether interleukin-9 worked through the JAK-STAT pathway,the expression of STAT3 protein was detected by western blot. RESULTS AND CONCLUSION:Micro-CT results showed the bone mass of interleukin-9 knockout mice decreased significantly compared with that of wild-type mice.In addition,the bone mineral density,bone volume fraction,trabecular number significantly decreased and trabecular separation markedly escalated in interleukin-9 knockout mice.The findings of hematoxylin-eosin staining were consistent with Micro-CT results.Interleukin-9 knockout mice had lower bone trabecular density.Type I collagen immunohistochemistry staining and Masson staining indicated the number of type Ⅰ collagen positive osteoblasts was significantly reduced and the capacity of collagen formation was damaged in interleukin-9 knockout mice.The results of colony-forming assay indicated that the mineralization capacity of osteoblast in interleukin-9 knockout mice were significantly lower than that in wild-type mice.Western blot results showed that osteogenesis induction activated STAT3 signaling,and the pSTAT3 level in wild-type mice with osteogenic induction was significantly higher than that in interleukin-9 knockout mice with osteogenic induction.These findings suggest that interleukin-9 regulates osteogenesis through the JAK-STAT3 pathway and interleukin-9 deficiency inhibits osteoblast differentiation and function,which may lead to reduced bone mass in interleukin-9 knockout mice.
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BACKGROUND:Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level,and the mechanism of related signaling pathways is an important way to further understand osteoporosis.At present,traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis.Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action. OBJECTIVE:To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature. METHODS:"Kaempferol,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathways"were used as Chinese and English search terms to search CNKI,WanFang,VIP,PubMed,Web of Science and Embase databases for relevant literature published from database inception to February 2023. RESULTS AND CONCLUSION:Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation,proliferation and apoptosis of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts.Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways.Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex.Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis.Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification.Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway.Kaempferol inhibits the expression of ERK,JNK,p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway,thus protecting osteogenesis.Kaempferol enhances the expression of osteogenic factors,bone morphogenetic protein-2,p-Smad1/5/8,β-catenin and Runx2,inhibits the expression of Peroxisome proliferation-activated receptor,and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.
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BACKGROUND:The pathogenesis of osteoporosis is complex,and its essence is the weakening of bone formation and the enhancement of bone absorption caused by various reasons,resulting in the imbalance of bone metabolism.In recent years,N6-methyladenosine has been found(N6-methyladenosine,m6A)methylation can prevent and treat osteoporosis by regulating bone metabolism. OBJECTIVE:Taking the regulation of bone metabolism by m6A methylation as an entry point,to systematically sort out and summarize the research progress of m6A methylation in osteoporosis,so as to provide certain theoretical reference bases for the search of new therapeutic targets for osteoporosis. METHODS:CNKI,WanFang,VIP,PubMed,MEDLINE,Nature,and Cochrane databases were retrieved for relevant literature published from database inception to 2023.The keywords were"osteoporosis,m6A methylation,bone metabolism,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English.Duplicates and obsolete non-referenced documents were excluded,and a total of 73 standard papers were included for further review. RESULTS AND CONCLUSION:m6A methylation can affect the activity and differentiation of bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts through various pathways to regulate bone metabolism and prevent osteoporosis.The regulatory process of m6A methylation is extremely complex,and its related proteins play different roles in different cells.Even in the same kind of cells,the same type of proteins may have radically different roles,regulating different physiological and pathological processes.
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BACKGROUND:Tissue engineering has brought new hope to the clinical challenge of liver failure,and the preparation of plant-derived decellularized fiber scaffolds holds significant importance in liver tissue engineering. OBJECTIVE:To prepare apple tissue decellularized scaffold material by using fresh apple slices and a solution of sodium dodecyl sulfate,and assess its biocompatibility. METHODS:Fresh apples were subjected to decellularization using phosphate buffer saline and sodium dodecyl sulfate solution,separately.Afterwards,the decellularized apple tissues and apple decellularized scaffold materials were decontaminated with phosphate buffer saline.Subsequently,scanning electron microscopy was used to assess the effectiveness of decellularization of the apple materials.Adipose-derived mesenchymal stem cells were extracted from the inguinal fat BALB/C of mice,and their expression of stem cell-related markers(CD45,CD34,CD73,CD90,and CD105)was identified through flow cytometry.The cells were then divided into a scaffold-free control group and a scaffold group.Equal amounts of adipose-derived mesenchymal stem cells were seeded onto both groups.The biocompatibility of the decellularized scaffold with adipose-derived mesenchymal stem cells was evaluated using CCK-8 assay,hematoxylin-eosin staining,and phalloidine staining.Cell adhesion and growth on the scaffold were observed under light microscopy and scanning electron microscopy.Furthermore,the scaffold was subdivided into the non-induced group and the hepatogenic-induced group.Adipose-derived mesenchymal stem cells were cultured on the decellularized apple scaffold,and they were cultured for 14 days in regular culture medium or hepatogenic induction medium for comparison.Immunofluorescent staining using liver cell markers,including albumin,cytokeratin 18,and CYP1A1,was performed.Enzyme-linked immunosorbent assay was used to detect the secretion of alpha fetoprotein and albumin.Additionally,scanning electron microscopy was employed to observe the morphology of the induced cells on the scaffold,verifying the expression of liver cell-related genes on the decellularized scaffold material.Finally,the cobalt-60 irradiated and sterilized decellularized apple scaffolds were transplanted onto the surface of mouse liver and the degradation of the scaffold was observed by gross observation and hematoxylin-eosin staining after 28 days. RESULTS AND CONCLUSION:(1)The scanning electron microscopy results revealed that the decellularized apple scaffold material retained a porous structure of approximately 100 μm in size,with no residual cells observed.(2)Through flow cytometry analysis,the cultured cells were identified as adipose-derived mesenchymal stem cells.(3)CCK-8 assay results demonstrated that the prepared decellularized apple tissue scaffold material exhibited no cytotoxicity.Hematoxylin-eosin staining and phalloidine staining showed that adipose-derived mesenchymal stem cells were capable of adhering and proliferating on the decellularized apple tissue scaffold.(4)The results obtained from immunofluorescence staining and enzyme-linked immunosorbent assay revealed that adipose-derived mesenchymal stem cells cultured on the decellularized apple scaffolds exhibited elevated expression of liver-specific proteins,including albumin,alpha-fetoprotein,cytokeratin 18,and CYP1A1.These results suggested that they were induced differentiation into hepatocyte-like cells possessing functional characteristics of liver cells.(5)The decellularized apple scaffold implanted at 7 days has integrated with the liver,with partial degradation of the scaffold observed.By 28 days,the decellularized apple scaffold has completely degraded and has been replaced by newly-formed tissue.(6)The results indicate that the decellularized scaffold material derived from apple tissue demonstrates favorable biocompatibility,promoting the proliferation,adhesion,and hepatic differentiation of adipose-derived mesenchymal stem cells.
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BACKGROUND:Osteoarthritis is one of the most common senile chronic degenerative diseases in China.Due to its complex pathogenesis and cellular molecular communication pathways,there is currently no effective method to slow down the progression of osteoarthritis.Studies have found that transforming growth factor-β is one of the key factors in the maintenance and regulation of joint stability and plays a significant role in the formation of early joints,as well as the development of bone and cartilage,and the remodeling of joints at various stages. OBJECTIVE:To review the regulatory role of the transforming growth factor-β subfamily in the occurrence and development of osteoarthritis,both domestically and internationally in recent years,to analyze the impacts it has at different stages of osteoarthritis,and to explore the potential application prospects of transforming growth factor-β in the clinical treatment of osteoarthritis,with a view to informing clinical treatment protocols.. METHODS:The relevant articles were searched by computer from CNKI Database and PubMed Database.The search terms were"osteoarthritis,transforming growth factor,signaling pathway,bone remodeling,cartilage degeneration,angiogenesis,treatment"in Chinese and English,respectively.Finally,57 articles were included for review. RESULTS AND CONCLUSION:The pathogenesis of osteoarthritis remains a subject of ongoing exploration with no unified consensus.Numerous studies highlight the close correlation between osteoarthritis and cytokines,focusing on the transforming growth factor-β superfamily as a pivotal mechanism and therapeutic breakthrough.Transforming growth factor-β plays a crucial role in early joint cartilage formation and maintenance,promoting cartilage repair.However,post-joint formation,its protective effect weakens,leading to potential destructive consequences.This dual regulatory role is a current clinical treatment focus,necessitating further research to delineate its application scope for standardized protocols.Highly active transforming growth factor-β participates in the regulation of bone cells,osteoblasts,and osteoclasts under mechanical stress,and intervenes in the subsequent remodeling of bone microstructure.Specific inhibitors present potential targeted therapeutics,yet their safety and efficacy in clinical settings require refinement.Vascular proliferation may serve as a potential disruptive pathway in transforming growth factor-β-mediated cartilage degeneration and subchondral bone remodeling.Abnormal communication pathways can further disrupt the homeostasis of the microenvironment of osteochondral units,thereby accelerating key pathological progressions of osteoarthritis.Research on transforming growth factor-β in osteoarthritic contexts is comprehensive,holding broad clinical application prospects.Drugs related to transforming growth factor-β are in clinical trial phases,but addressing potential impacts on other tissues and precise control of targeted delivery are critical concerns.As research advances,there is optimism for innovative breakthroughs in slowing the progression of osteoarthritis in the future.
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Exosomes are extracellular vesicles with a diameter of 40-100 nm, which contain a variety of functionally active substances such as proteins, microRNAs, and they are transported into the cell via different pathways. Studies have confirmed that exosomes slow down the progression of diabetic retinopathy by modifying changes in the levels of cell proliferation/apoptosis factors, antioxidant regulatory factors, inflammatory factors, and vascular endothelial growth factor in different ways, including direct regulation and delivery of different miRNAs, long-chained noncoding RNAs, which in turn inhibit high-glucose-induced retinal inflammation, neovascularization, microvascular damage, and vascular leakage and other retinal injuries caused by high glucose. This review summarizes the basic characteristics of exosomes and their research progress in diabetic retinopathy.
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【Objective】 To investigate the effect and mechanism of musk-containing serum on the migration of bone marrow mesenchymal stem cells (BMSCs). 【Methods】 Sixty SD rats were randomly divided into four groups: musk-high-, medium- and low-dose groups and blank control group; medicated serum was prepared. Fifteen SD rats were isolated and cultured with BMSCs, and the third generation of BMSCs were identified by morphology, phenotype, osteogenic and adipogenic induction. BMSCs received medicinal healing intervention with high-, medium- and low- (16.8, 8.4, and 4.2 μL/100 g) musk, and the cell proliferation rate was detected by MTT assay. Under the intervention of the protein kinase C (PKC) signaling pathway (GF109203X), the effect of musk with pharmacition on the migration of BMSCSs was detected with the Transwell test. 【Results】 The rat BMSCs were attached to the wall, with orderly arrangement and good cell viability. Phenotypic identification revealed that the expressions of CD44 and CD90 were positive, while the expressions of CD45 and CD34 were negative, and the cells could differentiate into osteoblasts and adipocytes. The proliferation rates of BMSCSs with different concentrations at different time periods were higher than those in the blank control group (P0.05). 【Conclusion】 The mechanism of musk-containing serum in promoting BMSCs migration may be related to the activation of PKC signaling pathway.
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ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases.
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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 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.