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1.
Article in English | WPRIM | ID: wpr-906679

ABSTRACT

@#BACKGROUND: Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury. Mesenchymal stem cell (MSC) transplantation is used to reduce tissue damage, but exosomes are more stable and highly conserved than MSCs. This study was conducted to investigate the therapeutic effects of MSC-derived exosomes (MSC-Exo) on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R), and to explore the underlying mechanisms. METHODS: Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment, with or without MSC-Exo treatment. Exosomal integration, cell viability, mitochondrial membrane potential, and generation of reactive oxygen species (ROS) were examined. Terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis. Moreover, mitochondrial function-associated gene expression, Nrf2 translocation, and expression of downstream antioxidant proteins were determined. RESULTS: MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation (P<0.05). The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus (2.14±0.65 vs. 5.48±1.09, P<0.01) and increased the intracellular expression of antioxidative proteins, including superoxide dismutase and glutathione peroxidase (17.18±0.97 vs. 14.40±0.62, and 20.65±2.23 vs. 16.44±2.05, respectively; P<0.05 for both). OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial function-associated genes, such as PINK, DJ1, LRRK2, Mfn-1, Mfn-2, and OPA1. The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons. CONCLUSIONS: MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons. Therefore, MSC-Exo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.

2.
Article in Chinese | WPRIM | ID: wpr-920560

ABSTRACT

Objective@#To explore the effects of red LEDs on the proliferation and osteogenic differentiation of human stem cells from apical papilla (hSCAPs).@*Methods@#hSCAPs were obtained by isolation, culture and flow cytometry in vitro and irradiated with 1, 3, 5, and 7 J/cm2 red LEDs. The proliferation of hSCAPs was detected using a CCK-8 assay. The osteogenic differentiation of hSCAPs was evaluated using alkaline phosphatase (ALP) staining, ALP activity assay and Alizarin red quantitative detection. The effect of 5 J/cm2 red LEDs on the expression levels of the ALP, Runx2, OCN, OPN and BSP genes and proteins was detected by RT-PCR and western blot, respectively.@*Results@# Red LEDs at 1, 3, 5, and 7 J/cm2 promoted the proliferation of hSCAPs (P < 0.05). The effects of red LEDs with different light energies on the proliferation of hSCAPs were different at different time points (P < 0.05). On the 7th and 14th days after irradiation, red LEDs promoted the osteogenic differentiation of hSCAPs, and the effect of 5 J/cm2 red LEDs was the most obvious under osteogenic induction culture conditions (P<0.05). Red LEDs (5 J/cm2) promoted the expression of the ALP, Runx2, OCN, OPN and BSP genes and proteins (P < 0.05).@*Conclusion @#Red LEDs promoted the proliferation and osteogenic differentiation of hSCAPs.

3.
Rev. cuba. hematol. inmunol. hemoter ; 37(2): e1237, 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1289429

ABSTRACT

Introducción: En el tejido adiposo se han identificado células madre mesenquimales con capacidad autorrenovadora y multipotencial. Mediante digestión enzimática y centrifugado del lipoaspirado se libera una población heterogénea de células denominada fracción vascular estromal, con innumerables potencialidades terapéuticas en el campo de la medicina regenerativa. Objetivo: Actualizar el alcance de las células madre derivadas de tejido adiposo en la terapia regenerativa. Método: Se revisaron 38 artículos entre los años 2000 y 2019 en las bases de datos Scielo, ScienceDirect, Medline y Pubmed. Desarrollo: Las células de la fracción vascular estromal se caracterizan por su capacidad de generar tejido adiposo y vasos sanguíneos, y por la producción de factores de crecimiento que ayudan en la supervivencia de los adipocitos y la formación de una red vascular. El principal mecanismo de acción de las células madre derivadas de tejido adiposo parece deberse a su acción paracrina y a la sinergia con células endoteliales. En el campo de la medicina regenerativa se han utilizado en el tratamiento de cicatrices patológicas y de fibrosis deformantes con impotencia funcional, en las reconstrucciones de secuelas por cáncer y en el cierre precoz de zonas cruentas. Conclusiones: La lipotransferencia es un procedimiento con un mínimo de complicaciones que constituye una de las opciones terapéuticas más empleadas para corregir defectos en los tejidos, debido a que no solo es un medio de relleno, sino que también permite la regeneración y restauración tisular. La presencia de células madre en el tejido adiposo, unido a su accesibilidad, disponibilidad e histocompatibilidad, ha motivado su aplicación cada vez más expandida en la medicina estética, reconstructiva y regenerativa(AU)


Introduction: Mesenchymal stem cells with self-renewing and multipotential capacity have been identified in adipose tissue. By means of enzymatic digestion and centrifugation of the lipoaspirate a heterogeneous population of cells called vascular stromal fraction is released. It has innumerable therapeutic potentialities in the field of regenerative medicine. Objective: To update the scope of stem cells derived from adipose tissue in regenerative therapy. Method: 38 articles published between 2000 and 2019 in the Scielo, ScienceDirect, Medline and Pubmed databases were reviewed. Development: The cells of the vascular stromal fraction are characterized by generating adipose tissue and blood vessels and by the production of growth factors that help in the survival of adipocytes and the formation of a vascular network. The main mechanism of action of stem cells derived from adipose tissue appears to be due to their paracrine action and synergy with endothelial cells. Stem cells derived from adipose tissue have been used in regenerative medicine for the treatment of pathological scars and deforming fibrosis with functional impotence, in the reconstruction of cancer sequelae and in the early closure of bloody areas. Conclusions: Lipotransfer is a procedure with a minimum of complications that constitutes one of the most widely used therapeutic options to correct tissue defects, since it is not only a filling medium, but also allows tissue regeneration and restoration. The presence of stem cells in adipose tissue, together with their accessibility, availability and histocompatibility, has motivated their increasingly widespread application in aesthetic, reconstructive and regenerative medicine(AU)


Subject(s)
Humans , Regeneration , Centrifugation , Adipocytes , Regenerative Medicine , Mesenchymal Stem Cells
4.
Cienc. Salud (St. Domingo) ; 5(2): [45-55], Ene-Abr. 2021. tab
Article in Spanish | LILACS | ID: biblio-1291442

ABSTRACT

Introducción: las células madre mesenquimatosas (CMM) se diferencian de diversos tipos celulares para la regeneración de tejidos, esta característica sumada con la versatilidad del antígeno leucocitario humano (HLA) representan una eficaz alternativa para el tratamiento de enfermedades con tejidos deteriorados. Se pueden obtener a partir de médula ósea, cordón umbilical (CU) y sangre fetal. Objetivo: analizar los tipos de diferenciación de las CMM, sus métodos de extracción y su relación con bancos de sangre de cordón umbilical (BSCU), a fin de demostrar la eficacia de las CMM, en patologías que impliquen alteración de algún tejido u órgano. Metodología: se revisaron varias publicaciones en español e inglés en Pubmed, Clinicalkey y Science Direct; desde 2013 hasta 2020. Se usaron los términos sangre fetal, células madre mesenquimatosas, trasplante de Células Madre de Sangre del Cordón Umbilical y bancos de sangre. Con dicha información se redactó un panorama amplio sobre las células mesenquimales y como estas participan en diversas áreas de la salud, con un énfasis importante en sus usos terapéuticos y lo referente a de donde provienen. Conclusión: a través de la pluripotencialidad de las CMM, se han podido emplear en múltiples patologías pues reestablece tejidos o líneas celulares exitosamente. Así mismo, los recursos para su obtención son claves en la tolerancia de los pacientes, por lo cual una gran opción para su obtención es el CU, que actualmente cuenta con bancos exclusivos para esto. (AU)


Introduction: mesenchymal stem cells (MSC) differentiate into multiple cell types for tissue regeneration, this characteristic added with the versatility of human leukocyte antigen (HLA) represent an effective alternative for the treatment of diseases with damaged tissues. They can be obtained from bone marrow, umbilical cord (UC), and fetal blood. Objetive: analyze the types of differentiation of MSC, their extraction methods and their relationship with umbilical cord blood banks (UCBB), in order to demonstrate the efficacy of MSC, in pathologies that involve alteration of a tissue or organ. Methodology: several publications in Spanish and English in Pubmed, Clinicalkey and Science Direct were reviewed; from 2013 to 2020. The terms fetal blood, mesenchymal stem cells, Umbilical Cord Blood Stem Cell transplantation and blood banks were used. With this information, a broad overview of mesenchymal cells and how they participate in various areas of health was drawn up, with an important emphasis on their therapeutic uses and where they come from. Conclusion: through the pluripotentiality of MSC, they have been used in multiple pathologies as it successfully re-establishes tissues or cell lines. Also, the resources for obtaining it are key in the tolerance of patients, which is why a great option for obtaining it is the UC, which currently has exclusive banks for this.


Subject(s)
Mesenchymal Stem Cells , Blood Banks , Fetal Blood
5.
Clinics ; 76: e2604, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249585

ABSTRACT

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.


Subject(s)
Humans , Coronavirus Infections , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Umbilical Cord , Pilot Projects , Betacoronavirus
6.
Article in Chinese | WPRIM | ID: wpr-882229

ABSTRACT

@#Periodontium regeneration and repair is a controversial and difficult point in the treatment of periodontosis. The proliferation, differentiation, migration and adhesion of periodontal ligament cells and the dynamic relationship between periodontal ligament cells and their extracellular matrix proteins are the basis of periodontium morphological reconstruction, functional maintenance and tissue repair. This article reviews the mechanism of estrogen-regulated periodontal membrane fine repair and periodontal tissue reconstruction to provide the basis for follow-up research on the treatment of periodontitis and the promotion of periodontal tissue repair and reconstruction by exogenous estrogen-mediated periodontal membranes. Under the regulation of certain concentrations of estrogen, the proliferation and differentiation ability of periodontal ligament stem cells (PDLSCs) and bone mesenchymal stem cells (BMSCs) to other periodontal ligament cells were enhanced. At the same time, PDLSCs, BMSCs, human periodontal ligament fibroblasts (HPLFSs), osteoblasts and cementoblasts synthesized and secreted collagen I (COLI), osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OCN) into the extracellular matrix. They interact with fibronectin (FN) and cementum attachment protein (CAP) in the extracellular matrix to form a variety of chain complexes and regulate each other, thus promoting the growth, migration, adhesion and fibrosis of periodontal ligament cells, repairing the collagen fiber skeleton of the periodontal ligament and adhering the two ends to the new cementum and the inherent alveolar bone.

7.
Acta cir. bras ; 36(12): e361206, 2021. graf
Article in English | LILACS-Express | MEDLINE, LILACSEXPRESS, LILACS, VETINDEX | ID: biblio-1355568

ABSTRACT

ABSTRACT Purpose: To evaluate whether the pigeon (Columba livia) is a good model for evaluating the vestibular system involved with postural maintenance during movement. Methods: This study maps the brainstem targets of the horizontal ampullary inputs from the vestibular periphery of the pigeon. We used biotin dextran amine (BDA) injection in horizontal semicircular canal (HSCC), immunohistochemistry for GluR2/3 and GluR4 AMPA and computerized histomorphology reconstruction. Results: Our results show the same distribution pattern with ipsilateral projections to vestibular nuclear complex (VNC) from the HSCC, with the majority of labeled fibers being, long, thin, with few varicosities and many ramifications. Horizontal semicircular canal projections achieve neurons belonging to all nuclei of the VNC with exception of dorsal portion of lateral vestibular nucleus and this area express GluR2/3 and GluR4 AMPA receptors reinforcing the idea of glutamate participation in these connections. Conclusions: Pigeon is an appropriated experimental model to study of projections of HSCC and reinforcing the information that the vestibular system has strong relation with the fast responses necessary for postural control. Moreover, its phylogenetic organization apparently conservation, also seems to be a fundamental characteristic for vertebrates.

8.
Article in Chinese | WPRIM | ID: wpr-905959

ABSTRACT

Objective:To investigate the effect of astragaloside Ⅳ(AST Ⅳ)and Notoginseng total saponins (NTS) combined with bone marrow mesenchymal stem cell (BMSC) transplantation on neural repair and angiogenesis in rats with cerebral ischemia. Method:The rats were randomly divided into a sham operation group, a model group, low- and high-dose AST Ⅳ + NTS groups, a BMSC infusion group, and low- and high-dose BMSC infusion+AST Ⅳ (10 and 20 mg·kg<sup>-1</sup>) + NTS group (25, 50 mg·kg<sup>-1</sup>). BMSCs were isolated and purified by whole bone marrow adherent culture. The positive expression of surface markers of BMSCs (CD29, CD90, CD34, and CD45) was detected by flow cytometry. The focal cerebral ischemia model was established by middle cerebral artery occlusion (MCAO). The PKH26-labeled BMSCs were injected into the tail vein of rats in the BMSC infusion group, once a day. The rats in the combination groups received BMSC injection once a day and intragastric administration of drugs twice a day. Other groups were administered twice a day by gavage. The sham operation group and the model group received the same amount of normal saline. Symptoms and signs of neurological deficits were assessed by the Longa method and the cerebral infarction rate was determined by TTC staining. The survival and vascularization [double positive expression of PKH26/vascular endothelial growth factor (VEGF)] after transplantation of BMSCs were observed by the immunofluorescence method. The protein expression of Ang1 and TGF-<italic>β</italic><sub>1</sub> was measured by Western blot. Result:BMSCs were properly isolated and cultured. The identification of surface markers CD29, CD90, CD34, and CD45 was consistent with the characteristics of BMSCs. The neurological deficit score and cerebral infarction rate of the model group were significantly increased (<italic>P</italic><0.01). All drugs and cell transplantation could alleviate the above pathological changes in varying degrees. The strongest effect was observed in high-dose BMSC infusion+AST Ⅳ+NTS group (<italic>P</italic><0.01), which was superior to those in the AST Ⅳ+NTS groups or the BMSC infusion group. BMSC injection helped cells survive in the ischemic brain tissues and promoted angiogenesis, and this effect could be enhanced by the combination with drugs. After cerebral ischemia, the expression of Ang1 and TGF-<italic>β</italic><sub>1</sub> was increased, and the effect in the BMSC infusion+AST Ⅳ+NTS groups was the strongest (<italic>P</italic><0.01). Conclusion:AST Ⅳ combined with NTS can promote the survival of transplanted BMSCs and facilitate angiogenesis after target repair of damaged blood vessels after cerebral ischemia. The mechanism may be related to the improvement of the local microenvironment in the brain after cerebral ischemia and the promotion of the survival and differentiation of transplanted stem cells.

9.
International Eye Science ; (12): 597-603, 2021.
Article in Chinese | WPRIM | ID: wpr-873852

ABSTRACT

@#AIM: To explore the differentiation of bone marrow-derived mesenchymal stem cells from peripheral blood to the retina and the expression of ciliary neurotrophic factor(CNTF). We also investigate the mechanism by which Bu Shen Yi Jing Fang could treat dry age-related macular degeneration(ARMD). <p>METHODS:C57BL/6 mice were administered with sodium iodate(NaIO3)by tail intravenous injection. One day after modeling, 3×106 green fluorescent protein labeled bone marrow-derived mesenchymal stem cells(GFP-BMSCs)were injected into the tail vein. The injected mice were randomly divided into distilled water group and Bu Shen Yi Jing Fang group according to random number table, and 12 mice in each group. The mice were intragastrical administrated with either Bu Shen Yi Jing Fang solution or distilled water every day. Twelve healthy C57BL/6 mice were fed regularly as the normal group. At 14d after the treatment, the differentiation of GFP-BMSCs in retina was determined by immunofluorescence, and the expression of CNTF in the retina was detected by immunofluorescence and quantitative real-time PCR.<p>RESULTS: Immunofluorescence staining showed that there were more glial fibrillary acidic protein(GFAP)and GFP double-stained positive cells in the Bu Shen Yi Jing Fang group than in the distilled water group(<i>P</i><0.01), and the positive rate of retinal pigment epithelium 65(RPE65)was not significantly different between two groups(<i>P</i>>0.05). There were no Rhodopsin and GFP double-stained positive cells in the two groups. Immunofluorescence and quantitative real-time PCR showed that the expression of CNTF in the Bu Shen Yi Jing Fang group was higher than which in the distilled water group(<i>P</i><0.05). <p>CONCLUSION: Bu Shen Yi Jing Fang facilitated the differentiation of peripheral blood stem cells into glial cells in the retina and the expression of CNTF, which might be one of the mechanisms of Bu Shen Yi Jing Fang in the treatment of dry ARMD.

10.
Article in Chinese | WPRIM | ID: wpr-848022

ABSTRACT

BACKGROUND: In recent years, the incidence of non-traumatic femoral head necrosis has increased gradually. It has the characteristics of insidious onset, rapid development of disease and high disability rate, bringing a great burden to patients, their families and society. Confirming its pathogenesis is of great significance for the early effective treatment of non-traumatic femoral head necrosis. OBJECTIVE: To review the relevant literature worldwide and to summarize the research progress of osteogenic signaling pathways in the pathogenesis of non-traumatic femoral head necrosis. METHODS: PubMed, Embase, Medline, CNKI, VIP and WanFang databases were retrieved with the keywords of “non-traumatic osteonecrosis of femoral head, osteogenesis, signaling pathways, pathogenesis, Wnt/β-catenin, PPARy, TGF-β/Smad, PI3K/AKT, MAPK, Notch” in English and Chinese, respectively. The articles concerning mechanism and application of osteogenic signaling pathways associated with avascular necrosis of the femoral head were included. RESULTS AND CONCLUSION: Recently, the role of osteogenic signaling pathways in non-traumatic femoral head necrosis has received increasing attentions. The abnormal differentiation of bone marrow mesenchymal stem cells in the development of non-traumatic femoral head necrosis has also become an issue of concern. Abnormal differentiation of bone marrow mesenchymal stem cells, inhibition of osteogenic differentiation, increased bone destruction, and imbalance of bone metabolism may be the main cause of non-traumatic femoral head necrosis, and Wnt/β-catenin, PPARy, TGF-β/Smad, PI3K/AKT, MAPK, Notch and other osteogenic signaling pathways may be a viable approach to intervention for non-traumatic femoral head necrosis. Although a large number of in vitro and animal studies have confirmed that osteogenic signaling pathway may have the potential to regulate bone marrow mesenchymal stem cell differentiation and reverse femoral head necrosis, its specific mechanism of action remains unclear and little is reported on its clinical applications. Therefore, exploring the mechanism of signaling pathways and accelerating its clinical use are the directions of the future research.

11.
Article in Chinese | WPRIM | ID: wpr-847225

ABSTRACT

BACKGROUND: Stem cell transplantation has a significant neuroprotective effect on neurological diseases. Current transplantation methods such as arteriovenous transplantation and brain stereotactic transplantation are not suitable for clinical application in preterm infants. OBJECTIVE: To explore the feasibility of nasal transplantation of human umbilical cord mesenchymal stem cells and human neural stem cells for the treatment of white matter injury in premature rat infants. METHODS: Human umbilical cord mesenchymal stem cells were prepared from human umbilical cord tissue, and human neural stem cells were prepared from human embryonic brain tissue. In vitro migration of two kinds of cells was assessed by Transwell method. Forty 3-day-old Sprague-Dawley rats were randomly divided into sham operation group, model control group, human umbilical cord mesenchymal stem cell transplantation group and human neural stem cell transplantation group, with 10 rats in each group. Rats in all groups except the sham operation group were treated with right common carotid artery ligation and hypoxia for 90 minutes to establish a rat model of white matter injury in the preterm infant. Totally 1×106 cells were delivered intranasally in the transplantation group at 3 days after injury. Each nostril was infused with 5×105, and each nostril was infused once. On day 7 after injury, MBP immunofluorescence staining was used to detect the expression of myelin basic protein in the white matter of the brain to identify the damage of the white matter injury model. At 24 hours after transplantation, human umbilical cord mesenchymal stem cell migration was detected by anti-HuNu immunohistochemical method and human neural stem cell migration was detected by CM-Dil fluorescent labeling method. RESULTS AND CONCLUSION: (1) On day 7 after modeling, compared with the normal side, the positive area of MBP decreased in cingulate band, corpus callosum and external capsule of the affected side in the model of brain white matter injury in preterm infants (P < 0.05), indicating a successful modeling. (2) In vitro experiments showed that the migration rate of human neural stem cells was the same as that of human umbilical cord mesenchymal stem cells. (3) At 24 hours after the nasal transplantation, human umbilical cord mesenchymal stem cells migrated to the cortex, corpus callosum and hippocampus on the normal side and the damaged side, and human neural stem cells migrated to the damaged cortex, corpus callosum and hippocampus, and human umbilical cord mesenchymal stem cells migrated more than human neural stem cells. (4) Overall, these findings indicate that 24 hours after the nasal transplantation, human umbilical cord mesenchymal stem cells could survive and migrate to the normal side and the injury side, and human neural stem cells could survive and migrate to the injury side; and the migration of human umbilical cord mesenchymal stem cells was more extensive than that of human neural stem cells.

12.
Article in Chinese | WPRIM | ID: wpr-847224

ABSTRACT

BACKGROUND: Thymus is an important central immune organ of human body, which is the place where T cells grow, develop and mature. Thymus is the first organ of senescence in human body, gradually atrophy and degeneration after puberty, followed by the gradual decline of immune function. OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells on the structure and function of thymus in the aging macaques. METHODS: Bone marrow was collected from female macaques with an average age of 3 years by bone marrow aspiration. Bone marrow mesenchymal stem cells were obtained by differential adherent culture. Five young macaques with an average age of 3 years were used as the young group. Ten aging macaques with an average age of 25 years were randomly divided into elderly group (n=4) and elderly treatment group (n=6). The macaques in the elderly treatment group were infused with bone marrow mesenchymal stem cells (1 × 107 cells/kg) through the femoral vein, and were infused every other day for three consecutive times. Macaques of the young group and the elderly group were infused with the same volume of saline at the same time. The changes of output and secretion levels of the subgroup of thymocytes in the elderly treatment group after infusion, thymic index, thymic tissue structure and collagen fiber deposition in each group were analyzed. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cell transplantation increased thymus index, T cell output level and reduced regulatory T cells, improved thymus secretion function, increased thymosin alpha and thymosin II secretion. The thymus parenchyma area increased; the skin and medulla junction appeared; part of the thymus tissue was regenerated and transformed to normal structure; the degree of thymus tissue fibrosis was reduced; and collagen fiber deposition was reduced. These results indicate that bone marrow mesenchymal stem cell transplantation can improve the structure and function of thymus in aging macaques.

13.
Article in Chinese | WPRIM | ID: wpr-847222

ABSTRACT

BACKGROUND: Studies have shown that mesenchymal stem cells can participate in the repair of wound injury caused by diabetes, but the high glucose environment obviously inhibits the function of mesenchymal stem cells and the effect of transplantation. OBJECTIVE: To observe the effect of conditioned medium of bone marrow mesenchymal stem cells intervened by rosiglitazone on the proliferation and migration of endothelial progenitor cells in high glucose environment. METHODS: (1) The bone marrow mesenchymal stem cells from the logarithmic growth period were cultured in three groups. The normal group was cultured with alpha-MEM medium containing 10% fetal bovine serum. The high glucose group was cultured with alpha-MEM medium containing 10% fetal bovine serum and 25 mmol/L glucose. The rosiglitazone group was cultured with alpha-MEM medium containing 10% fetal bovine serum, 25 mmol/L glucose and 10 μmol/L rosiglitazone. After 48 hours of culture, the culture supernatant was extracted as conditioned medium. The levels of vascular endothelial growth factor and matrix cell derived factor 1 in conditioned medium were detected by ELISA. (2) The endothelial progenitor cells from the logarithmic growth period were divided into three groups. The control group was cultured with the EGM-2 MV medium containing 10% fetal bovine serum. The model group was cultured with the EGM-2 MV medium containing 10% fetal bovine serum, 30 mmol/L glucose and conditioned medium of the high glucose group. The experimental group was cultured with EGM-2 MV medium containing 10% fetal bovine serum, 30 mmol/L glucose and conditioned medium of the rosiglitazone group. After 24 hours of culture, the ability of cell proliferation and migration was detected. RESULTS AND CONCLUSION: (1) The levels of vascular endothelial growth factor and matrix cell derived factor 1 in the conditioned medium of high glucose group were significantly lower than that of the normal group (P < 0.05). The levels of vascular endothelial growth factor and matrix cell derived factor 1 in the conditioned medium of the rosiglitazone group were significantly higher than in the high glucose group (P < 0.05). (2) The proliferation and migration ability of endothelial progenitor cells in the model group was lower than that in the control group (P < 0.05). The proliferation and migration ability of endothelial progenitor cells in the experimental group was higher than that in the model group (P < 0.05). (3) It is suggested that the conditioned medium of rosiglitazone intervened bone marrow mesenchymal stem cells can promote the proliferation and migration of endothelial progenitor cells.

14.
Article in Chinese | WPRIM | ID: wpr-847218

ABSTRACT

BACKGROUND: The treatment and prognosis of traumatic brain injury are difficult points in clinical work at present. More and more studies have shown that exosomes derived from stem cells show unique advantages in traumatic brain injury, which may have greater neurotherapeutic potential in the treatment of traumatic brain injury, and may essentially restore neurovascular function and promote neuronal regeneration, thereby providing new ideas for the treatment of traumatic brain injury. OBJECTIVE: To review the application and advantages of exosomes derived from stem cells in traumatic brain injury. METHODS: A computer-based search was performed in the PubMed and CNKI databases for articles addressing exosomes. The keywords were “Traumatic brain injury, Exosomes, Stem cells” in English and Chinese, respectively. Finally, 53 articles were included for review. RESULTS AND CONCLUSION: (1) A large number of traumatic brain injury animal experiments proved that nerve cells and stem cells can secrete exosomes. (2) Exosomes derived from nerve cells and stem cells play a positive role in the treatment of traumatic brain injury, but the exosomes derived from stem cells are more effective in nerve, vascular regeneration and neurofunctional recovery. (3) The exosomes derived from stem cells may open up a new approach to traumatic brain injury.

15.
Article in Chinese | WPRIM | ID: wpr-847217

ABSTRACT

BACKGROUND: Bone marrow mesenchymal stem cells induce osteogenesis and inhibit adipocyte differentiation, which is the key to the prevention and treatment of osteoporosis and the source of seed cells for bone tissue repair engineering. Wnt signaling pathway plays an important role in bone formation. OBJECTIVE: To review the related factors and molecular mechanisms that regulate osteogenic differentiation of bone marrow mesenchymal stem cells through Wnt/β-catenin signaling pathway. METHODS: CNKI, PubMed and Wanfang Medical Database were retrieved by computer for related literatures published from inception to February 2020. The Chinese key words were “bone marrow mesenchymal stem cells, osteoporosis, osteogenic differentiation, osteocytes, extracellular matrix, osteoarthritis, Wnt, β-catenin”. The English key words were “BMSCs, osteoarthritis, Wnt/β-catenin, Wnt”. Finally, 62 articles were included in the review. RESULTS AND CONCLUSION: The relevant factors can directly or indirectly regulate the osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β-catenin signaling pathway. There are positive promotion, negative inhibition and even loop regulation due to the interaction between various factors. The Wnt/β-catenin signaling pathway is a key signal for osteogenic differentiation of bone marrow mesenchymal stem cells. The systematic analysis of the molecular mechanism of osteogenic differentiation of bone marrow mesenchymal stem cells provides a theoretical basis for bone tissue engineering, and can realize the application of bone tissue engineering faster.

16.
Article in Chinese | WPRIM | ID: wpr-847216

ABSTRACT

BACKGROUND: Systemic lupus erythematosus is an autoimmune disease with unknown causes. To establish a tree shrew model of systemic lupus erythematosus is helpful to understand its pathogenesis and provide evidence for stem cell transplantation in the treatment of autoimmune diseases. OBJECTIVE: To establish a tree shrew model of systemic lupus erythematosus and to assess the therapeutic effect of umbilical cord mesenchymal stem cell transplantation. METHODS: Tree shrews were grouped and intraperitoneally injected pristane, lipopolysaccharide, and their combination. At 3 weeks after injection, 12 tree shrew models were divided into treatment group and model control group (n=6 per group). An additional 6 models were selected as a normal control group. In the treatment group, each tree shrew was injected with 1×106 DiR-labeled umbilical cord mesenchymal stem cells through caudal vein. Two weeks later, the heart, liver, spleen, lung and kidney of tree shrews were taken for pathological sections. The sections received hematoxylin-eosin staining, kidney Masson staining and immune complex detection. Simultaneously, the heart, liver, spleen, lung and kidney of the three groups of tree shrews were taken for in vitro imaging. RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining showed pathological changes of the heart, liver, spleen, lung and kidney in the model control group; and there were a lot of immune complex deposits in renal tissue in the model control group. The pathological changes in the treatment group improved, and the structure recovered to close to the normal control group. (2) In vitro imaging showed that DiR-labeled cells were mainly distributed in the lung, liver and spleen of the tree shrews in the treatment group. The fluorescence intensity of tree shrews in the treatment group was significantly higher than that in the normal control group and model control group (P < 0.05). (3) Results demonstrated that intraperitoneal injection of pristane and lipopolysaccharide is the best method to induce pathological changes of systemic lupus erythematosus in tree shrews. The pathological changes after treatment with umbilical cord mesenchymal stem cells have improved, indicating that umbilical cord mesenchymal stem cells have certain treatment effects on tree shrew models of systemic lupus erythematosus.

17.
Article in Chinese | WPRIM | ID: wpr-847215

ABSTRACT

BACKGROUND: Skin transplantation is one of the most effective methods for treating large-area burns. How to effectively suppress the immune rejection after allogeneic skin transplantation is a problem that needs to be solved urgently. OBJECTIVE: To investigate the effect of human adipose derived mesenchymal stem cells (hADSCs) on the immunoregulation of skin grafts in different strains of mice. METHODS: Isolated hADSCs were cultured to the 3rd generation. Sixty ICR neonatal mice, 2-4 days of age, were randomly divided into four groups (n=15). The skin tissues of ICR neonatal mice were transplanted into adult C57BL/6 mice to establish a different strain of mouse skin graft immune rejection model. PBS and low dose (5×104), medium dose (10×104), high dose (20×104) hADSCs were injected into the model mice through tail vein, and the survival time of transplanted skin in each group was recorded. On the 7th day after operation, five mice from each group were randomly selected to remove their spleen and serum, and the expression of immune factors interleukin-10, tumor necrosis factor-α and interferon-γ were detected by RT-PCR and ELISA respectively. The transplanted part of the skin was taken to make pathological sections for observing the infiltration of lymphocytes. RESULTS AND CONCLUSION: Compared with the PBS group, the survival time of the skin was prolonged in the low dose hADSCs group; however, there was no significant difference between the two groups (P > 0.05). Compared with the PBS and low dose hADSCs groups, the survival time of the skin was significantly increased in the medium and high dose groups (P 0.05). Compared with the PBS group, the relative expression of tumor necrosis factor-α and interferon-γ in the spleen and serum was significantly decreased in the low, medium and high dose hADSCs groups (P < 0.05), whereas the level of interleukin-10 was significantly elevated in the medium and high dose hADSCs groups (P < 0.05). To conclude, the appropriate dose of hADSCs can significantly prolong the survival time of transplanted skin between different strains of mice, by regulating the expression of related immune factors in the recipient mice.

18.
Article in Chinese | WPRIM | ID: wpr-847211

ABSTRACT

BACKGROUND: Transplanting islet-like cells induced by human umbilical cord mesenchymal stem cells (hUC-MSCs) into type 1 diabetic mice can reduce blood glucose level and improve the symptoms of diabetes mellitus. However, there are few reports on intraperitoneal transplantation. OBJECTIVE: To study the therapeutic effect of transplantation of islet-like cells induced by hUC-MSCs in different ways for the treatment of type 1 diabetic mice. METHODS: The hUC-MSCs were isolated and cultured by tissue explants adherent method and differentiated into islet-like cells. The 3 of 15 male C57BL/6J mice were used as normal group, and the remaining mice were taken to prepare a mouse model of type 1 diabetes using intraperitoneal injection of streptozotocin. After successful modeling, nine model mice were randomly divided into diabetes group, tail vein-islet-like cells group, and abdomen-islet-like cells group, with three mice in each group. After 10 days of modeling, the normal group and diabetic group were not treated. The tail vein-islet-like cells group was injected with 5×105 cells/0.4 mL islet-like cells via the tail vein and the abdomen-islet-like cells group was intraperitoneally injected with 5×105 cells/0.4 mL islet-like cells. During the treatment, the blood glucose and insulin levels were measured twice a week; glucose tolerance test was performed at 28 days after cell transplantation; and fasting insulin level was detected at 42 days after cell transplantation. RESULTS AND CONCLUSION: (1) Compared with the diabetic group, in the tail vein-islet-like cells group, the blood glucose level began to decrease on the 10th day after transplantation and maintained until the 31st day, and the insulin level and glucose tolerance significantly improved (P < 0.05). However, there was no significant improvement in blood glucose level, insulin level and glucose tolerance in the abdomen-islet-like cells group. (2) To conclude, transplantation of hUC-MSCs induced islet-like cells for the treatment of type 1 diabetic mice via tail vein is an ideal transplantation method, and the effect of intraperitoneal injection is unsatisfactory.

19.
Article in Chinese | WPRIM | ID: wpr-847210

ABSTRACT

BACKGROUND: It is widely accepted to recruit mesenchymal stem cells from the jaws to repair the defects of the jaws. However, there are relatively few researches on orofacial-bone-derived mesenchymal stem cells, mainly due to the difficulty in separating mesenchymal stem cells from the jaws. OBJECTIVE: To establish the methods of in vitro isolation and culture of rat orofacial-bone-derived mesenchymal stem cells and observe and study its related biological characteristics. METHODS: The mandibles of rats were dissected. The attached muscles were stripped and cut into pieces. Cortical bone was loosened by digesting with collagenase II. The migration and adherent growth ability of mesenchymal stem cells was used to isolate orofacial-bone-derived mesenchymal stem cells. Cell morphology was observed by inverted microscope. Surface markers of the cell were detected by flow cytometry. Cell proliferation was detected by MTT assay and cell growth curve was drawn. Fibroblast colony forming rate was calculated by colony formation. Osteogenic and lipogenic induction experiments were conducted to study the multi-directional differentiation potential of cells. RESULTS AND CONCLUSION: Cells isolated by collagenase digestion and bone slice culture were positive for CD29, CD44 and Sca-1, and negative for CD31, CD34 and CD45. Cell proliferation test showed that the growth curves of orofacial-bone-derived mesenchymal stem cells exhibited incubation period, logarithmic phase and platform period. In addition, the cells had a strong ability of proliferation, and the cell clone formation rate was 20% and the cells in DNA synthesis stage accounted for 52.5%. Alizarin red and oil red O staining showed positive reaction after osteogenic and lipogenic induction, indicating that the cells have the potential of multi-directional differentiation. It is concluded that the method of bone fragment culture after digestion with collagenase II could separate orofacial-bone-derived mesenchymal stem cells sufficiently and purely. Besides, the orofacial-bone-derived mesenchymal stem cells show strong proliferative and osteogenic differentiation capacities. Thus, it provides abundant source of seed cells for bone tissue engineering of maxillofacial represented by bone defects repairing of implants.

20.
Article in Chinese | WPRIM | ID: wpr-847209

ABSTRACT

BACKGROUND: The growth pattern of Echinococcus granulosus is different from that of Echinococcus alveolaris. Hepatic echinococcosis can form a complete fibrous calcified cyst wall, while hepatic alveolar echinococcosis can grow infiltratively and cannot form a complete fibrous calcified cyst wall. Bone marrow mesenchymal stem cells (BMSCs) are involved in the formation of calcified wall of hydatidosis, but the calcification characteristics of Echinococcus granulosus and Echinococcus alveolaris are different and the role of BMSCs is still unclear. OBJECTIVE: To compare the effects of Echinococcus granulosus and Echinococcus alveolaris on the calcification of BMSCs and to preliminarily investigate the formation mechanism of echinococcosis calcifications. METHODS: BMSCs of C57BL/6 mice were extracted, cultured and identified, followed by co-culture with the protoscolex of Echinococcus granulosus (BMSC+CE group) and Echinococcus alveolaris (BMSC+AE group), respectively. BMSCs cultured alone were used as control group. After 1, 4, and 7 days of co-culture, alkaline phosphatase activity was detected by a microplate reader, the expression of BMP2 and RUNX2 mRNA was detected by RT-q PCR, and the expression of BMP2, RUNX2 and phosphorylated Smad1/5/8 (P-Smad1/5/8) proteins was detected by western blot assay. RESULTS AND CONCLUSION: (1) The alkaline phosphatase activity of the BMSC+CE group and BMSC+AE group was significantly higher than that of the control group at 1 and 4 days after culture (P < 0.05), and the alkaline phosphatase activity of the BMSC+CE group was significantly higher than that of BMSC+AE group (P < 0.05). (2) Western blot results showed that the expression of BMP2, RUNX2, and P-Smad1/5/8 protein in the BMSC+CE group and BMSC+AE group was significantly higher than that in the control group at 1 and 4 days after culture (P < 0.05), while the expression of BMP2, RUNX2, and P-Smad1/5/8 protein in the BMSC+CE group was significantly higher than that in the BMSC+AE group (P < 0.05). (3) RT-qPCR results showed that the expression of BMP2 and RUNX2 mRNA in the BMSC+CE group was significantly higher than that in the control group at 1, 4 and 7 days after culture (P < 0.05), and was significantly higher than that in the BMSC+AE group at 4 and 7 days after culture (P < 0.05). The expression of RUNX2 mRNA in the BMSC+AE group was significantly higher than that in the control group at 1, 4, and 7 days after culture (P < 0.05). (4) To conclude, co-culture of the protoscolex of Echinococcus alveolaris and BMSCs promotes the expression of alkaline phosphatase and RUNX2 in BMSCs by up-regulating BMP-Smad1/5/8 pathway. At the later stage of co-culture, the effect of Echinococcus alveolaris on BMSCs calcification is significantly weakened, while the effect of Echinococcus granulosus on BMSCs calcification remains unchanged, suggesting that this mechanism may be related to the different growth patterns of two kinds of hydatids.

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