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Background Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown. Results In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1. Conclusions Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis.
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Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.
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Humans , Antioxidants/metabolism , Ferroptosis , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Iron Overload/metabolismABSTRACT
With the multi-directional differentiation potential such as osteogenic differentiation, chondrogenic differentiation and adipogenic differentiation, mesenchymal stem cells (MSCs) have been widely used in basic research and clinical applications. The differentiation potential of MSCs is altered during senescence. Osteogenic differentiation potential decreases, while the lipogenic differentiation potential increases in aging MSCs. Changes in differentiation potential of MSCs during senescence are accompanied with cell physical heterogeneity variation (cell size, cell stiffness and nucleoplasmic ratio). Studies have shown that changes in physical heterogeneity of stem cells may be a key factor leading to the differences in differentiation potential of MSCs. Therefore, studies on physical heterogeneity variation of MSCs during senescence will provide a new research direction in fate prediction of stem cell. In this review, the effects of physical heterogeneity variation on differentiation potential of MSCs were summarized, and the corresponding mechanism was also discussed.
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Abstract Objectives Osteoblasts are derived from Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs), which play an indispensable role in bone formation. In this study, the authors aim to investigate the role of IRF4 in the osteogenic differentiation of BM-MSCs and its potential molecular mechanism. Methods The authors used lentivirus infection to overexpress IRF4 in BM-MSCs. The expression of IRF4 and osteogenesis-related genes were detected by qRT-PCR and western blot analysis. The osteogenic differentiation of BM-MSCs was evaluated by Alkaline Phosphatase (ALP) activity, Alizarin red staining, and Alkaline Phosphatase (ALP) staining. Chromatin Immunoprecipitation (ChIP), Dual-Luciferase reporter assay and RNA Immunoprecipitation Assay were applied to confirm the regulatory mechanism between IRF4, miR-636 and DOCK9. Results The authors found IRF4 was down-regulated during the osteogenic differentiation of BM-MSCs, and IRF4 overexpression could decrease the osteogenic differentiation of BM-MSCs by specifically promoting the reduction of Alkaline Phosphatase (ALP) activity and down-regulating osteogenic indicators, including OCN, OPN, Runx2 and CollA1. Mechanistically, IRF4 activated microRNA-636 (miR-636) expression via binding to its promoter region, and Dedicator of Cytokinesis 9 (DOCK9) was identified as the target of miR-636 in BM-MSCs. Moreover, the damage in the capacity of osteogenic differentiation of BM-MSCs induced by IRF4 overexpression could be rescued by miR-636 inhibition. Conclusions In summary, this paper proposed that IRF4/miR-636/DOCK9 may be considered as targets for the treatment of osteoporosis (OP).
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Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.
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【Objective】 To explore the establishment methods of transgenic human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing tumor necrosis factor(TNF)-related apoptosis-inducing ligand (TRAIL) based on the transposons, and attempt to apply it on the nude mice mode with glioma. 【Methods】 PiggyBac transposon system specially designed by us was used to prepare non-targeting and Her2-targeting hUC-MSCs that can stably express TRAIL through puromycin screening. The glioma cells expressing firefly luciferase (U87MG-LUC) were injected into the skull of the immunodeficient mice (BALB/c-nu/nu) with 1×106 cells per mouse. After 7 days of injection, the mice transplanted with U87MG were detected with a small animal living imager to determine the size and location of the tumors in skull. Then we injected the glioma-transplantation nude mouse with two kinds of transgenic hUC-MSCs expressing TRAIL (named as untarget-TRAIL and target-TRAIL, respectively), or the non-transgenic hUC-MSCs (all 1×106 cells per mouse) or PBS (named as WT-MSCs and PBS for negative control) respectively, and then monitored the changes of tumor signals by a small animal living imager every week for 3~4 weeks. 【Results】 After six passages to expand the cells, the both transgenic cell lines can stably express TRAIL gene. Their ratio of green fluorescent protein (GFP) positive cells can reach 93%-97%, and the positive ratio of their MSC-specific surface markers still maintained normal (CD34+, CD45+, and HLA-DR+ all <0.1%, CD90>99%, CD73>88%, and CD105 >60%). The median survival time (d) of U87MG-transplanted nude mice in the groups of untarget-TRAIL, target-TRAIL, WT-MSCs, and PBS was 41 vs 39 vs 24 vs 23(P<0.05). 【Conclusion】 The transgenic hUC-MSCs overexpressing TRAIL gene can significantly prolong the survival time of nude mice with brain glioma.
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Background: Diesel vehicles exhaust contains toxic nanoparticles that drastically affect lung tissue due to their direct cytotoxic effects, induction of oxidative stress, inflammatory signaling pathways and DNA damage. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory effects and efficient regenerative capacity in chronic lung diseases. Objectives: Evaluation of the effects of MSCs and MSCs-derived micro vesicles (MSCs-MVs) on pulmonary toxicity induced by diesel exhaust nanoparticles (DENPs). Materials and Methods: Sixty male rats were equally divided into: Group I (Control rats), Group II (DENPs group) received repeated doses of DENPs (180μg/rat) intratracheally every other day for 6 days, Group III (MSCs group) received MSCs intravenously (3×106 cells) after the last dose of DENPs and Group IV (MSCs-MVs group) received MSCs-MVs (0.5 mg/mL) intravenously after the last dose of DENPs. Lung tissue were subjected to histological and immunohistochemical assessment. Inflammatory cytokines and bronchoalveolar lavage fluid (BALF) contents of inflammatory cells, albumin, LDH and total proteins were evaluated. Results: Histological picture of lung tissue in DENPs group showed numerous collapsed alveoli, thick interalveolar septa and marked cellular infiltration. Elastic fibers were markedly decreased by DENPs. Increased optical density of NF-κB/p65 immunoreactivity. Bronchoalveolar lavage fluid showed significant elevation of inflammatory cytokines (TNF-a, IL-6), polymorphonuclear leukocytes (PMN), neutrophils, macrophages, LDH, total proteins and albumin. Treatment with either MSCs or MSCs-MVs led to a significant amelioration of all of the aforementioned studied parameters. Conclusion: MSCs-MVs and MSCs showed significant therapeutic effects against DENPs damaging effects on the lung tissues via their regenerative capacity and anti-inflammatory effects.
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Icariin, a prenylated flavonol glycoside isolated from Epimedium, has been considered as a potential alternative therapy for osteoporosis. The present study aimed to clarify the detailed molecular mechanisms of action of icariin on osteoblast function, using bone marrow-derived mesenchymal stem cells (BM-MSCs). BM-MSCs were first stimulated by icariin. Then, gene and protein expression of cAMP/PKA/CREB signaling molecules were analyzed by RT-PCR and western blotting (WB), and alkaline phosphatase (ALP) was analyzed in cell lysates by ELISA. MTT assays indicated that icariin did not have significant effects on cell viability up to 1 µM. Icariin showed a dose-dependent effect on the alkaline phosphatase activity of BM-MSCs. WB analysis showed that icariin treatment of BM-MSCs significantly enhanced the protein expression of protein kinase A (PKA) and cAMP-responsive element binding protein (CREB), while RT-PCR results showed that icariin dose-dependently increased the mRNA levels of PKA and CREB. Icariin induced BM-MSC differentiation by BMP2, Smad1, and Runx2. RT-PCR and WB results indicated that icariin significantly increased the expression of BMP2, Smad1, and Runx2 in BM-MSCs. These results suggest that icariin is an agonist of the cAMP/PKA/CREB pathway in BM-MSC differentiation, raising the possibility that it could be used in the treatment of osteoporosis.
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Cirrhosis is an advanced stage of liver fibrosis that causes fatal complications and and threats human health.Liver transplantation is the preferred treatment method of cirrhosis patients,but the therapeutic effect of liver transplantation is limited.In recent years,researchers at home and abroad have proposed the concept of cell replacement therapy for liver cirrhosis.Among them,mesenchymal stem cells (MSCs) have a wide range of sources,the MSCs can inhibit immunity and reduce the infiltration of inflammatory cells and release of pro-inflammatory cytokines,and they can also be induced to differentiate into hepatocytes to mitigate fibrosis,which become the preferred drug of cell replacement therapy for cirrhosis.Here,we mainly reviewed the mesenchymal stem cells from the features,the mechanisms of treatment for cirrhosis,and recent experimental studies and clinical trials.
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Wharton's jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have immunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medicine.
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Humans , Embryonic Stem Cells , Ethics , Graft vs Host Disease , Hematopoietic Stem Cells , Immunomodulation , Mesenchymal Stem Cells , Regenerative Medicine , Stem Cells , Umbilical Cord , Wharton JellyABSTRACT
BACKGROUND: Mesenchymal stem cells (MSCs) can be used for a wide range of therapeutic applications because of not only their differentiation potential but also their ability to secrete bioactive factors. Recently, several studies have suggested the use of human embryonic stem cell-derived MSCs (hE-MSCs) as an alternative for regenerative cellular therapy due to mass production of MSCs from a single donor. METHODS: We generated hE-MSCs from embryonic stem cell lines, SNUhES3, and analyzed immune properties of these cells. Also, we evaluated the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease. RESULTS: The cell showed the suppression of immunity associated with allogenic peripheral blood mononuclear cells in mixed lymphocyte response assay. We also detected that cytokines and growth factor related to the immune response were secreted from these cells. To assessed the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease, we used imiquimod (IMQ)-induced skin psoriasis mouse model. The score of clinical skin was significantly reduced in the hE-MSCs treated group compared with control IMQ group. In histological analysis, the IMQ-induced epidermal thickness was significantly decreased by hE-MSCs treatment. It was correlated with splenomegaly induced by IMQ which was also improved in the hE-MSCs. Moreover, IMQ-induced inflammatory cytokines; Th1 cytokines (TNF-α, IFN-α, IFN-γ,and IL-27) and Th17 cytokines (IL-17A and IL-23), in the serum and skin showed marked inhibition by hEMSCs. CONCLUSION: These results suggested that hE-MSCs have a potency of immune modulation in psoriasis, which might be the key factor for the improved psoriasis.
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Animals , Humans , Mice , Cytokines , Embryonic Stem Cells , Lymphocytes , Mesenchymal Stem Cells , Psoriasis , Skin Diseases , Skin , Splenomegaly , Tissue DonorsABSTRACT
Aim To study the relationship between WntlOb and bone morphogenetic protein-9 (BMP9)-induced osteogenic differentiation of mesenchymal stem cells (MSCs), and the molecular mechanisms underlying this process. Methods PCR, Western blot and histochemical staining were used to detect the effect of BMP9 on WntlOb and the effect of WntlOb on BMP9-induced osteogenic differentiation in MSCs. Meanwhile, real-time PCR, Western blot, oil red O staining, and flow cytometry assay were used to analyze the potential mechanism of Wnt10b affecting the function of BMP9. Results Wnt10b could be detected in C3H10T1/2, C2C12, MEFs and MC3T3-E1 cells. BMP9 up-regulated the expression of WntlOb in C3H10T1/2 cells. WntlOb enhanced the capability of BMP9 to increase the level of OCN and mineralization in C3H10T1/2 cells, and silencing Wnt10b attenuated these effects of BMP9. Wnt10b exhibited no substantial effect on cell cycle affected by BMP9, but it enhanced the effect of BMP9 on inducing phosphorylation of Smadl/5/8. While silencing Wnt10b attenuated this effect of BMP9. In addition, Wnt10b inhibited BMP9-induced adipogenic differentiation in C3H10T1/2 cells, and silencing Wnt10b promoted this effect of BMP9. Conclusions Wnt10b can promote BMP9-induced osteogenic differentiation of MSCs, which may be mediated through enhancing BMP/Smad signaling and reducing adipogenic differentiation.
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BACKGROUND: Mesenchymal stem cells (MSCs) and/or biological scaffolds have been used to regenerate articular cartilage with variable success. In the present study we evaluated cartilage regeneration using a combination of bone marrow (BM)-MSCs, Hyalofast™ and/or native cartilage tissue following full thickness surgical cartilage defect in rabbits. METHODS: Full-thickness surgical ablation of the medial-tibial cartilage was performed in New Zealand white (NZW) rabbits. Control rabbits (Group-I) received no treatment; Animals in other groups were treated as follows. Group-II: BMMSCs (1 × 10⁶ cells) + Hyalofast™; Group-III: BMMSCs (1 × 10⁶ cells) + cartilage pellet (CP); and Group-IV: BMMSCs (1 × 10⁶ cells) + Hyalofast™+ CP. Animals were sacrificed at 12 weeks and cartilage regeneration analyzed using histopathology, International Cartilage Repair Society (ICRS-II) score, magnetic resonance observation of cartilage repair tissue (MOCART) score and biomechanical studies. RESULTS: Gross images showed good tissue repair (Groups IV>III>Group II) and histology demonstrated intact superficial layer, normal chondrocyte arrangement, tidemark and cartilage matrix staining (Groups III and IV) compared to the untreated control (Group I) respectively. ICRS-II score was 52.5, 65.0, 66 and 75% (Groups I–IV) and the MOCART score was 50.0, 73.75 and 76.25 (Groups II–IV) respectively. Biomechanical properties of the regenerated cartilage tissue in Group IV closed resembled that of a normal cartilage. CONCLUSION: Hyalofast™ together with BM-MSCs and CP led to efficient cartilage regeneration following full thickness surgical ablation of tibial articular cartilage in vivo in rabbits. Presence of hyaluronic acid in the scaffold and native microenvironment cues probably facilitated differentiation and integration of BM-MSCs.
Subject(s)
Animals , Rabbits , Bone Marrow , Cartilage , Cartilage, Articular , Chondrocytes , Cues , Hyaluronic Acid , Mesenchymal Stem Cells , New Zealand , Osteoarthritis , RegenerationABSTRACT
Allergic rhinitis (AR) is an allergic disease of nasal mucosa, currently the consensus has been reached that there is a Th1/Th2 imbalance in AR′s pathogenesis, meanwhile there are defects in the number and/or function of Treg cells. Mesenchymal stem cells (MSCs) have characteristics of multiple differentiation potential, low immunogenicity and immunomodulation function, which can be migrated and implanted into the nasal inflammatory mucosal, recovering the Th1/Th2 immune balance and up-regulate the Treg cells by immunomodulatory function to improve AR. For the present, the treatment of AR by MSCs is basically at the animal experiment stage. This paper reviews the progress of MSCs in AR′s treatment and provides a basis for the clinical treatment of MSCs.
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Objective To compare mobilization effects of endogeneous MSCs in the treatment of ulcerative colitis rats by Shenling Baizhu Powder and Tongxie Yaofang Decoction. Methods Twenty SD male rats were randomly divided into blank group, model group, Shenling Baizhu Powder group and Tongxie Yaofang Decoction group. TNBS/ethanol method was used to build the ulcerative colitis model. Administration groups were given Shenling Baizhu Powder and Tongxie Yaofang Decoction for gavage and model group and blank group were given normal saline for gavage. After gavage, MSCs from peripheral blood and bone marrow were extracted for primary culture. MSCs of bone marrow and peripheral blood were detected by flow cytometry. Results MSCs from bone marrow showed: Compared with the blank group, the percentage of positive cells in the model group decreased (P<0.05); Compared with the model group, the percentage of positive cells in Shenling Baizhu Powder group and Tongxie Yaofang Decoction group increased, and the expression of Shenling Baizhu Powder group was more obvious (P<0.05). MSCs from peripheral blood showed: Compared with the blank group, the percentage of positive cells in the model group increased (P<0.05); Compared with the model group, the percentage of positive cells in Shenling Baizhu Powder group and Tongxie Yaofang Decoction group decreased, and the expression of Shenling Baizhu Powder group was more obvious (P<0.05). Conclusion Shenling Baizhu Powder and Tongxie Yaofang Decoction have the function of promoting the increase of bone marrow-derived MSCs and the reduction of peripheral blood source of MSCs in model rats, and Shenling Baizhu Powder is better than Tongxie Yaofang Decoction.
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Mechanosensitive (MS) channels are extensively studied membrane protein for maintaining intracellular homeostasis through translocating solutes and ions across the membrane, but its mechanisms of channel gating and ion selectivity are largely unknown. Here, we identified the YnaI channel as the Na/K cation-selective MS channel and solved its structure at 3.8 Å by cryo-EM single-particle method. YnaI exhibits low conductance among the family of MS channels in E. coli, and shares a similar overall heptamer structure fold with previously studied MscS channels. By combining structural based mutagenesis, quantum mechanical and electrophysiological characterizations, we revealed that ion selective filter formed by seven hydrophobic methionine (YnaI) in the transmembrane pore determined ion selectivity, and both ion selectivity and gating of YnaI channel were affected by accompanying anions in solution. Further quantum simulation and functional validation support that the distinct binding energies with various anions to YnaI facilitate Na/K pass through, which was defined as binding-block mechanism. Our structural and functional studies provided a new perspective for understanding the mechanism of how MS channels select ions driven by mechanical force.
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Cryoelectron Microscopy , Escherichia coli Proteins , Chemistry , Metabolism , Ion Channels , Chemistry , Metabolism , Mechanotransduction, Cellular , Models, Molecular , Quantum TheoryABSTRACT
Cell sheets technology is being available for fracture healing. This study was performed to clarify bone healing mechanism of undifferentiated (UCS) and osteogenic (OCS) differentiated mesenchymal stromal cell (MSC) sheets in the fracture model of dogs. UCS and OCS were harvested at 10 days of culture. Transverse fractures at the radius of six beagle dogs were assigned into three groups (n = 4 in each group) i.e. UCS, OCS and control. The fractures were fixed with a 2.7 mm locking plate and six screws. Cell sheets were wrapped around the fracture site. Bones were harvested 8 weeks after operation, then scanned by micro-computed tomography (micro-CT) and analyzed histopathologically. The micro-CT revealed different aspects of bone regeneration among the groups. The percentages of external callus volume out of total bone volume in control, UCS, and OCS groups were 42.1, 13.0 and 4.9% (p < 0.05) respectively. However, the percentages of limbs having connectivity of gaps were 25, 12.5 and 75% respectively. In histopathological assessments, OCS group showed well organized and mature woven bone with peripheral cartilage at the fracture site, whereas control group showed cartilage formation without bone maturation or ossification at the fracture site. Meanwhile, fracture site was only filled with fibrous connective tissue without endochondral ossification and bone formation in UCS group. It was suggested that the MSC sheets reduced the quantity of external callus, and OCS induced the primary bone healing.
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Animals , Dogs , Bone Regeneration , Bony Callus , Cartilage , Connective Tissue , Extremities , Fracture Healing , Mesenchymal Stem Cells , Osteogenesis , RadiusABSTRACT
Objective To investigate the effect of nuclear factor erythroid-2-related factor 2(Nrf2) on the anti-hypoxia and anti-apoptotic ability of mesenchymal stem cells(MSCs). Methods Human embryonic kidney cells(293FT) were transfected with recombinant plasmid which overexpressed Nrf2 and helper plasmid. High-titer lentivirus which overexpressed Nrf2 were obtained. MSCs were transfected with lentivirus with Nrf2 overexpression and empty lentiviral vector to establish Nrf2-MSCs which stably overexpressed Nrf2 (Nrf2 overexpression group) and green fluorescent protein (GFP)-MSCs(control group). The expression of green fluorescent in 2 groups was observed by fluorescence microscope. The expression level of Nrf2 protein in 2 groups was measured by Western Blot. The anti-hypoxia ability of 2 groups was observed by light microscope. The anti-apoptotic ability of 2 groups was measured by flow cytometry. Results Nrf2-MSCs which stably overexpressed Nrf2 were successfully established. Western Blot analysis revealed that the expression level of Nrf2 protein in the Nrf2 overexpression group was significantly higher than that in the control group(P<0.01). After 15 h hypoxia treatment, the cell activity in the Nrf2 overexpression group was significantly higher than that in the control group. Flow cytometry showed that the apoptosis rate in the Nrf2 overexpression group was (30.9±1.4)%, significantly lower than (61.3±1.3)% in the control group(P<0.05). Conclusions Nrf2-MSCs which can stably overexpress Nrf2 possess certain anti-hypoxia and anti-apoptotic ability in hypoxia environment.
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Objective:To explore mechanisms underlying the rescuing effects of transplanted mesenchymal stem cells (MSCs) derived exosomes on estrogen-deficient osteoporosis.Methods:Mouse estrogen-deficient osteoporosis model was constructed in 12 female C57BL6/J rats and the exosome release was regulated by siRNA.Osteogenic induction,alizarin red staining and qPCR were performed to evaluate the effects of exosomes on recipient MSC functions.The miR-26a mimics and inhibitors and qPCR were used to explore the mechanisms underlying exosome-mediated functional rescue of recipient MSCs.Results:Donor MSCs alleviated estrogen-deficient osteoporosis via exosome release,and the alleviated osteoporosis by exosomes rescued the recipient MSC functions were observed.Moreover,the rescued recipient MSC functions by exosomes transferred miR-26a were found.Conclusion:Donor MSC-derived exosomes may rescue MSC functions and may remit osteoporosis of the recipient through transfering miR-26a.
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Objective To explore the security of exosome derived from human umbilical cord mesenchymal stem cell(huc-MSC-exosome)as a kind of biological product on clinical application.Methods huc-MSC-exosome were separated by ultea centrifuge. CD9 and CD63 expression of huc-MSC-exosome were tested by Western-blot.Nanoparticle analysis was used to detect the size and concentration of huc-MSC-exosome.Hemolytic experiment,systemic anaphylaxis and blood routine test were used to verify the self-safety of huc-MSC-exosome.Results huc-MSC-exosome expressed specific markers of exosome,CD9 and CD63.Moreover,huc-MSC-exosome cannot result in hemolysis,systemic anaphylaxis reaction and abnormality of blood routine test.Conclusion Exosome derived from human umbilical cord mesenchymal stem cell has general signs of exosomes and possesses the certainly security,which may provide the experimental evidence for huc-MSC-exosome clinical application.