BACKGROUND:Aging of human body may be due to the senescence and depletion of various stem cells in the body.Bone marrow mesenchymal stromal cells have important physiological functions and have shown certain therapeutic effects on various diseases.It is of great significance to study the senescence and mechanism of bone marrow mesenchymal stromal cells.OBJECTIVE:To investigate whether human bone marrow mesenchymal stromal cells exhibit senescence phenotypes with increasing donor age,and further determine whether endogenous retrovirus drives the senescence of bone marrow mesenchymal stromal cells,offering a novel reference for the investigation of stem cell senescence mechanism.METHODS:The senescence of bone marrow mesenchymal stromal cells at different ages was characterized by flow cytometry,β-galactosidase staining,qPCR,western blotting,and EdU fluorescence imaging.Bone marrow mesenchymal stromal cells and cell culture supernatant were collected from donors of different ages.The content of human endogenous retrovirus was detected by qPCR.Furthermore,highly sensitive droplet digital PCR was used to detect the expression of endogenous retrovirus-like particles in the cell culture supernatant.The content of endogenous retrovirus in bone marrow plasma samples of different ages was detected by ELISA.RESULTS AND CONCLUSION:Bone marrow mesenchymal stromal cells exhibited obvious senescence with increasing age,including significant morphological changes,increased proportion of β-galactosidase positive cells,increased expression of senescence markers P16 and P21 protein,decreased expression of LMNB1 protein,and reduced cell proliferation ability.There was no significant difference in the content of endogenous retrovirus in bone marrow mesenchymal stromal cells at different ages,almost no endogenous retrovirus-like particles in the cell culture supernatant.There was no significant difference in endogenous retrovirus-like particles detected in bone marrow plasma samples at different ages.These findings indicate that human bone marrow mesenchymal stromal cells have normal physiological senescence with increasing age,but the mechanism of senescence is not mediated by abnormal activation of endogenous retroviruses,which may have a more complex driving mechanism.

BACKGROUND:Aging of human body may be due to the senescence and depletion of various stem cells in the body.Bone marrow mesenchymal stromal cells have important physiological functions and have shown certain therapeutic effects on various diseases.It is of great significance to study the senescence and mechanism of bone marrow mesenchymal stromal cells.OBJECTIVE:To investigate whether human bone marrow mesenchymal stromal cells exhibit senescence phenotypes with increasing donor age,and further determine whether endogenous retrovirus drives the senescence of bone marrow mesenchymal stromal cells,offering a novel reference for the investigation of stem cell senescence mechanism.METHODS:The senescence of bone marrow mesenchymal stromal cells at different ages was characterized by flow cytometry,β-galactosidase staining,qPCR,western blotting,and EdU fluorescence imaging.Bone marrow mesenchymal stromal cells and cell culture supernatant were collected from donors of different ages.The content of human endogenous retrovirus was detected by qPCR.Furthermore,highly sensitive droplet digital PCR was used to detect the expression of endogenous retrovirus-like particles in the cell culture supernatant.The content of endogenous retrovirus in bone marrow plasma samples of different ages was detected by ELISA.RESULTS AND CONCLUSION:Bone marrow mesenchymal stromal cells exhibited obvious senescence with increasing age,including significant morphological changes,increased proportion of β-galactosidase positive cells,increased expression of senescence markers P16 and P21 protein,decreased expression of LMNB1 protein,and reduced cell proliferation ability.There was no significant difference in the content of endogenous retrovirus in bone marrow mesenchymal stromal cells at different ages,almost no endogenous retrovirus-like particles in the cell culture supernatant.There was no significant difference in endogenous retrovirus-like particles detected in bone marrow plasma samples at different ages.These findings indicate that human bone marrow mesenchymal stromal cells have normal physiological senescence with increasing age,but the mechanism of senescence is not mediated by abnormal activation of endogenous retroviruses,which may have a more complex driving mechanism.

BACKGROUND:Mesenchymal stem cells have been widely used in the treatment of various diseases due to their wide range of sources,their ease of proliferation in vitro and their ability to secrete a range of immunomodulatory factors to suppress inflammation and promote tissue repair and regeneration.However,in the treatment of many diseases,the therapeutic effect is limited.The effort to engineer and modify mesenchymal stem cells for specific disease pathogenesis or intervention targets is an important development for cell therapy in the future.OBJECTIVE:Interleukin-10 is a typical anti-inflammatory cytokine that helps to modulate the immune response and induces macrophage polarization towards an anti-inflammatory phenotype.This study investigated the therapeutic effect of interleukin-10 engineered human umbilical cord mesenchymal stem cells on inflammatory bowel disease.METHODS:Human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were established by electro-transfection,and screened for clinical-grade cells based on the cell therapy product criteria.C57BL/6J mice were given 5%aqueous dextran sulfate sodium ad libitum to establish a model of acute colitis.Empty plasmid-transfected human umbilical cord mesenchymal stem cells or interleukin-10-human umbilical cord mesenchymal stem cells(1×106 cells/each mouse)were injected on day 1 before modeling(tail vein injection)and day 4(intraperitoneal injection)after modeling,respectively.On day 6 after modeling,colon tissue sections were taken for hematoxylin-eosin staining to assess histological changes.Immunofluorescence staining was performed to detect the expression of proliferating cell nuclear antigen and CD31.RESULTS AND CONCLUSION:The engineered human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were constructed,and met the quality standard of clinical-grade human umbilical cord mesenchymal stem cells.Human umbilical cord mesenchymal stem cells could repair acute colitis in mice.The therapeutic effect of interleukin-10-human umbilical cord mesenchymal stem cells was more efficacious,which more significantly suppressed body weight loss(P<0.05),colon shortening(P<0.05),and damage of colonic tissues(P<0.05)in acute colitis mice.In interleukin-10-human umbilical cord mesenchymal stem cell treatment group,there were significantly more proliferating cell nuclear antigen-positive cells and CD31-positive cells in the colon sections than in the human umbilical cord mesenchymal stem cell treatment group,suggesting that interleukin-10-overexpressing human umbilical cord mesenchymal stem cells contributed to the repair of colon tissue by significantly promoting the proliferation of intestinal tissues and angiogenesis.

BACKGROUND:Mesenchymal stem cells have been widely used in the treatment of various diseases due to their wide range of sources,their ease of proliferation in vitro and their ability to secrete a range of immunomodulatory factors to suppress inflammation and promote tissue repair and regeneration.However,in the treatment of many diseases,the therapeutic effect is limited.The effort to engineer and modify mesenchymal stem cells for specific disease pathogenesis or intervention targets is an important development for cell therapy in the future.OBJECTIVE:Interleukin-10 is a typical anti-inflammatory cytokine that helps to modulate the immune response and induces macrophage polarization towards an anti-inflammatory phenotype.This study investigated the therapeutic effect of interleukin-10 engineered human umbilical cord mesenchymal stem cells on inflammatory bowel disease.METHODS:Human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were established by electro-transfection,and screened for clinical-grade cells based on the cell therapy product criteria.C57BL/6J mice were given 5%aqueous dextran sulfate sodium ad libitum to establish a model of acute colitis.Empty plasmid-transfected human umbilical cord mesenchymal stem cells or interleukin-10-human umbilical cord mesenchymal stem cells(1×106 cells/each mouse)were injected on day 1 before modeling(tail vein injection)and day 4(intraperitoneal injection)after modeling,respectively.On day 6 after modeling,colon tissue sections were taken for hematoxylin-eosin staining to assess histological changes.Immunofluorescence staining was performed to detect the expression of proliferating cell nuclear antigen and CD31.RESULTS AND CONCLUSION:The engineered human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were constructed,and met the quality standard of clinical-grade human umbilical cord mesenchymal stem cells.Human umbilical cord mesenchymal stem cells could repair acute colitis in mice.The therapeutic effect of interleukin-10-human umbilical cord mesenchymal stem cells was more efficacious,which more significantly suppressed body weight loss(P<0.05),colon shortening(P<0.05),and damage of colonic tissues(P<0.05)in acute colitis mice.In interleukin-10-human umbilical cord mesenchymal stem cell treatment group,there were significantly more proliferating cell nuclear antigen-positive cells and CD31-positive cells in the colon sections than in the human umbilical cord mesenchymal stem cell treatment group,suggesting that interleukin-10-overexpressing human umbilical cord mesenchymal stem cells contributed to the repair of colon tissue by significantly promoting the proliferation of intestinal tissues and angiogenesis.

BACKGROUND: The placental tissue structure is complex, including the amniotic membrane, chorion, and decidua from the mother. Mesenchymal stem cells derived from different tissues of the same placenta have been reported to have similar biological characteristics. To date, there is no study regarding quantitative comparison of differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. OBJECTIVE: To investigate the biological characteristics including differentiation potential and immunomodulatory function of mesenchymal stem cells derived from different tissues of human placenta. METHODS: The amnion-, chorion-, and decidua-derived mesenchymal stem cells were isolated from the placental tissue of a baby boy by enzymatic digestion method. The biological characteristics of these three kinds of mesenchymal stem cells were systematically investigated including cell morphology, immunophenotypes, karyotypeanalysis, adipogenic and osteogenic differentiation potential, and Treg cells proliferation capacity. RESULTS AND CONCLUSION: All three kinds of mesenchymal stem cells showed fibroblast-like morphology and expressed the surface markers of mesenchymal stem cells with high expressions of CD73, CD90 and CD105, as well as low expressions of CD14, CD19, CD34, CD45 and HLA-DR. The karyotypes of the amnion-and chorion-derived mesenchymal stem cells were the same as the fetus, and decidua-derived mesenchymal stem cells had the same karyotype as the mother. There were significant differences in adipogenic differentiation capacity between three kinds of mesenchymal stem cells (amnion-derived mesenchymal stem cells> chorion-derived mesenchymal stem cells> decidua-derived mesenchymal stem cells; P < 0.05). In contrast, the osteogenic differentiation capacity of amnion-derived mesenchymal stem cells was remarkably higher than that of decidua-derived mesenchymal stem cells (P < 0.05). The amnion-and chorion-derived mesenchymal stem cells had the higher potential of Treg cell proliferation induction than decidua-derived mesenchymal stem cells. These findings indicate that three sources of human placenta-derived mesenchymal stem cells have different karyotypes, adipogenic and osteogenic differentiation potential, and immunomodulatory capability, providing a variety of ideal seed cell sources for disease treatment.

Lyotropic liquid crystal system is formed by the amphiphilic molecules dissolving in polar solvents with a special geometric structure. Lamellar, cubic and hexagonal mesophases are some of the most common lyotropic liquid crystal systems. Recently, they have attracted much research attention because of their distinctive structures and physico-chemical properties(like strong bioadhesion, high permeability, low liquidity, and slow released drug), and have been widely used as carriers for drug delivery systems, especially in transdermal and mucosal fields. According to the research about lyotropic liquid crystal and nasal route of administration in our group, and the related references in recent years, we investigate the technical strategies about the using of lyotropic liquid crystal in transdermal and mucosal drug delivery system. Among them, we specially put the emphasis on the application prospects of lyotropic liquid crystal in the nasal mucosal administration, and then provide a theoretical basis and future research directions in the development of lyotropic liquid crystal in transdermal and mucosal administration fields.