Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires ...Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC hominghas been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms.展开更多
Background Heart failure due to ischemic heart disease is still a major health problem. Myocardium regeneration emerges as a novel therapeutic method for treating myocardial infarction （MI）. However, it is affected ...Background Heart failure due to ischemic heart disease is still a major health problem. Myocardium regeneration emerges as a novel therapeutic method for treating myocardial infarction （MI）. However, it is affected by many factors. The present study was aimed to investigate the effect of chemokine stromal cell-derived factor 1 （SDF-1）/CXCL12 on mesenchymal stem cells （MSCs） homing to injured myocardium in a rat myocardial infarction model. Methods A rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with bromodeoxyuridine. The rats were divided into two groups. SDF-1 expression was measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1, 2, 4, 7, 14 and 28 days post operation in the SDF-1 detection group. The rats in the intervention groups were injected with SDF-1, anti-SDF-1 antibody or saline 4 days after myocardial infarction. Then, a total of 5×10^6 cells in 2.5 ml of phosphate-buffered saline were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted on the 3rd day post injection. Cardiac function and blood vessel density were assessed on the 28th day post injection. Results Self-generating SDF-1 expression was increased at the first day post MI, peaked at the 7th day and decreased thereafter while it remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than in the non-MI group （P=0.000）; the MSCs enrichment in the host hearts were more abundant in the SDF-1 injected group than in the anti-SDF-1 antibody and saline injected groups （P = 0.000）. Cardiac function was improved more in the SDF-1 injected group than in the anti-SDF-1 antibody and saline injected groups （P = 0.000）. Neovascularization in the SDF-1 injected group increased significantly compared to the other groups （P= 0.000）. Conclusion My展开更多
Objective:To investigate the effects of panax notoginseng saponins(PNS) on homing of C-kit+ bone mesenchymal stem cells(BMSCs) to the infarction heart.Methods:The acute myocardial infraction(AMI) model was established...Objective:To investigate the effects of panax notoginseng saponins(PNS) on homing of C-kit+ bone mesenchymal stem cells(BMSCs) to the infarction heart.Methods:The acute myocardial infraction(AMI) model was established in 140 Wistar rats,105 model rats survived after operation,and the model rats were randomly divided into five groups,21 rats in each group:Western medicine group mobilized by subcutaneous injection of human granuloctye colony stimulating factor(G-CSF) 50 μg·kg-1·d-1;sham operation group and a model group treated by subcutaneous injection of normal saline 50 μg·kg-1·d-1;Chinese medicine group mobilized by intraperitoneal injection of Xuesaitong(血塞通)(ingredients of PNS) 150 mg·kg-1·d-1;integrative medicine group mobilized by subcutaneous injection of G-CSF 50 μg·kg-1·d-1 and intraperitoneal injection of Xuesaitong 150 mg·kg-1·d-1.Except for the sham-operated group,each group was divided into three sub-groups by three time points of 1 d,7 d and 14 d.G-CSF was injected once a day for 7 d.Xuesaitong was injected once a day until the rats were killed.The flow cytometry was used for detection of C-kit + cells in the peripheral blood in different time points,and immunohistochemical method was used for detection of the changes of C-kit + cell and Ki-67+ cell numbers in the marginal zone of AMI.Results:Twenty-four hours after the operation,C-kit + cells had a slight increase in the model group compared with the sham operation group(P>0.05).The peripheral blood C-kit+ cells in the integrative group increased significantly compared with the other groups on 7 d and 14 d(all P<0.05).Meanwhile the expression of C-kit + cells and Ki-67+ cells in the marginal zone of AMI in the integrative group increased significantly compared with the Chinese medicine group,the western medicine group and the model group on 1 d,7 d and 14 d(all P<0.05),and the cells in the integrative group decreased significantly on 14 d compared with that on 7 d(P<0.05).Conclusion:PNS can cooperate with G-CSF to mobilize C-kit+展开更多
A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated？ Can adult stem cells be...A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated？ Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth？ If not, what are the therapeutically viable sources of stem cells for tooth regeneration？ Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration？ How can regenerated teeth be economically competitive with dental implants？ Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide？ This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration： repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes.展开更多
Objective： To investigate the effect of Huogu II Formula （活骨 II方 ） with medicinal guide Radix Achyranthis Bidentatae （Ach） on bone marrow stem cells （BMSCs） homing to necrosis area after osteonecrosis of the...Objective： To investigate the effect of Huogu II Formula （活骨 II方 ） with medicinal guide Radix Achyranthis Bidentatae （Ach） on bone marrow stem cells （BMSCs） homing to necrosis area after osteonecrosis of the femoral head （ONFH） frozen by liquid nitrogen in rabbit as well as to explore the mechanism of prevention and treatment for ONFH. Methods： The animal model of ONFH was established by liquid nitrogen frozen on the rabbit left hind leg. Forty-eight Japanese White rabbits were randomly assigned to sham-operated group, model group, Huogu II group, and Huogu II plus Ach group, with 12 rabbits in each. During the course of ONFH animal model establishment, all rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor [rhG-CSF, 30 μg/（kg.day） for continuous 7 days]. Meanwhile, normal saline and decoction of the two formulae were administrated by gavage, respectively. White blood cells （WBC） were counted in peripheral blood before and after injection of rhG-CSF. Materials were drawn on the 2rid and 4th weeks after model built; bone glutamine protein （BGP） and bone morphogenetic protein 2 （BMP2） levels in serum were tested. Histopathologic changes were observed by hematoxylin and eosin （HE） staining. BMP2 mRNA levels were detected with in situ hybridization （iSH） staining. 5-Bromo-2＇-deoxyuridine （BrdU） and stromal cell derived factor 1 （SDF-1） were measured by immunohistochemical assay in femoral head of the left hind leg. Results： Compared with the shamoperated group, the ratio of empty lacuna, serum BGP, and SDF-1 level in the model group increased significantly, and BMP2 in both serum and femoral head decreased significantly. However, in comparison with the model group, the empty lacuna ratio of Huogu II group and Huogu II plus Ach group decreased obviously in addition to the levels of serum BGP and BMP2, and the expressions of BMP2 mRNA, BrdU, and SDF-1 increased significantly. Above changes were particularly obv展开更多
Preferential infection and depletion of gut-homing a4β7 CD4＋ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing a4p7 CD4＋ T cells and their functional subsets during th...Preferential infection and depletion of gut-homing a4β7 CD4＋ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing a4p7 CD4＋ T cells and their functional subsets during the acute stages of HIV-1 infection are less documented. Therefore, we conducted a cohort study to investigate whether acute HIV-1 infection induced abnormalities in gut-homing a4β7 CD4＋ T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing a4β7 CD4＋ T cells in 26 acute HIV-l-infected patients compared with 20 healthy individuals. We found that circulating gut-homing a4β7 CD4＋ T cells were preferentially depleted during acute HIV-1 infection and were positively correlated with absolute CD4＋ T-cell count in blood. Notably, Th17 and Thl cell subsets of gut-homing CD4＋ T cells were also decreased, which resulted in an imbalance of T helper cells （Th 1）-regulatory T cells （Treg） and Treg.Th 17 ratios. Gut-homing Th17 and Thl cells were also positively correlated with the absolute number of total CD4＋ T cells and gut-homing CD4＋ T cells. The gut-homing Treg：Th17 ratio was inversely correlated with the CD4＋ T-cell count. Taken together, the analyses of our acute HIV-1 cohort demonstrate that gut-homing a4β7 CD4＋ T cells and their functional subsets were profoundly depleted during acute HIV-1 infection, which may have resulted in the persistent loss of circulating CD4＋ T cells and an imbalance of Thl-Treg and Treg.Th17 ratios and contribute to HIV-1 disease pathogenesis.展开更多
Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis treatment.However,limited sources and poor tissue-homing efficiency limit their clinical capabilities.In this study,we isolated a ki...Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis treatment.However,limited sources and poor tissue-homing efficiency limit their clinical capabilities.In this study,we isolated a kind of MSCs from women’s menstrual blood(MenSCs)noninvasively and established a novel MSCs bone marrow-targeted delivery system by utilizing waterin-oil-in-water droplet microfluidics.MenSCs were encapsulated withinβ-cyclodextrin-functionalized alginate microcapsules loaded with zoledronates,which has a high affinity for bone.With this delivery system,MenSCs could be preferentially delivered to the bone marrow tissues via intravenous infusion,and restored bone mass by remodeling the bone marrow niche in situ in ovariectomized mouse models.Moreover,scRNA-seq analysis demonstrated that those MenSCs homed to the bone marrow recruited CD4^(+)FOXP3^(+)natural regulatory T(nT_(reg))cells by secreting CCL28.The recruited nTreg promoted CD8^(+)T cells to secret Wnt family member 10B(WNT10B),activating the Wnt signaling in osteoblasts and thus promoting bone formation in situ in the bone marrow.This study reveals a promising application of MenSCs in postmenopausal osteoporosis treatment and highlights the clinical value of MenSCs by encouraging women to reserve autologous MenSCs before menopause to prevent and alleviate postmenopausal osteoporosis.展开更多
Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. Thes...Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like "wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed.展开更多
OBJECTIVE: To investigate the effects of Ermiao Fang(EM) with medical guide Xixin(Herba Asari Mandshurici)(HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis(OA) rats.METHODS: OA rats were induc...OBJECTIVE: To investigate the effects of Ermiao Fang(EM) with medical guide Xixin(Herba Asari Mandshurici)(HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis(OA) rats.METHODS: OA rats were induced by arthrectomy and assigned to sham-operated, model, EM, or EM plus HAM groups.All rats were injected with recombinant human granulocyte colony-stimulating factor 30μg·kg-1·d-1for7 days and treated with EMor EM plus HAM at 1.6 or 1.9 g·kg-1·d-1 for 3 or 6 weeks, respectively. Chondrocyte apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Levels of interleukin-1 beta(IL-1β) tumor necrosis factor alpha(TNF-α) nitric oxide(NO), and inducible nitric oxide synthase(iNOS) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay. Matrix metalloproteinases(MMPs)-13,tissue inhibitors of metalloproteinases(TIMPs)-1,Bromodeoxyuridine(BrdU), cluster of differentiation 34(CD34), and stromal cell-derived factor 1(SDF-1) were measured by immunohistochemical assay.RESULTS:The EM and EM plus HAM groups had significantly less cartilage damage and synovium inflammation the model group. Moreover, the EM and EM plus HAM groups had less chondrocyte apoptosis and more proteoglycan and collagen content than the model group.The EM and EMplus HAM groups had obviously higher MMPs-13 and TIMPs-1 expression in the cartilage than the model group. Moreover, the two formula groups had less release of IL-1β, TNF-α, NO, and iNOS than model group. Importantly, the expressions of BrdU, CD34,and SDF-1 in cartilage were significantly higher in the EM and EM plus HAM-Medtreated rats than model group. Notably, the EM plus HAM treatment seemed to have the greatest effects.CONCLUSION: HAM improves the therapeutic effects of EM on OA rats by enhancing BMSC directional homing to the focal zone.展开更多
In this paper, we propose the role of mesenchymal stem cells in fracture repair. We investigated the role of bone marrow mesenchymal stem cells in the healing process of fracture and the effect on the migration of end...In this paper, we propose the role of mesenchymal stem cells in fracture repair. We investigated the role of bone marrow mesenchymal stem cells in the healing process of fracture and the effect on the migration of endogenous bone marrow mesenchymal stem cells. Experiments show that exogenous bone marrow mesenchymal stem cells implanted in femur fractures in vivo can make endogenous bone marrow mesenchymal stem cells in vitro migration ability and fracture site of nerve growth factor expression increased, which promotes rat fracture healing.展开更多
Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missin...Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missing from the rodent endometrium. Interestingly, CD62L (L-selectin)-deficient BALB/c mice delivered significantly higher numbers of viable offspring than wild type controls via mechanisms yet to be defined. Methods: Nulliparous CD62L-deficient (8-10-week-old, n = 25) or wild type (n = 18) females were mated with 43 age-matched males. Animals were sacrificed at gestational day (GD) 9.5. Tissue samples were analyzed by immunostaining and flow cytometry. Results: Mating wild type and CD62L-deficient BALB/c mice revealed that the increased birth rate was due to the CD62L deficiency in females. Flow cytometric analysis demonstrated significant differences in the number of natural killer (NK) cells present in the uterus of pregnant CD62L- deficient mice compared to controls. Immunohistochemistry confirmed NK cell accumulation at the fetal-maternal interface. Discussion: Uterine NK cells have been shown to peak at GD 8-10 at the fetal-maternal interface. NK cells might regulate mouse fertility rates by facilitating development of the maternal spiral arteries, thereby stimulating the formation of larger vessels that facilitate intrauterine survival, however, their role is not obligate to spiral artery development. Conclusions: Diminished CD62L expression modified immune cell trafficking into the uterus of pregnant mice generating a microenvironment primarily dominated by NK cells resulting in improved embryonic survival rates.展开更多
Objective：To investigate the effect of MCP-1 on mesenchymal stem cells（MSCs） homing to injured myocardium in a rat myocardial infarction（MI） model. Methods：Rat myocardial infarction model was established by perm...Objective：To investigate the effect of MCP-1 on mesenchymal stem cells（MSCs） homing to injured myocardium in a rat myocardial infarction（MI） model. Methods：Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU. The Rats were divided into two groups. Monocyte chemotactic protein I（MCP-1） expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1, 2, 4, 7, 14 and 28 days post operation in MCP-1 detection group. The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group. Then, a total of 5 × 10^6 cells in 2.5 ml of PBS were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel density were assessed 28 days post injection. Results：Self-generating MCP-1 expression was increased at the first day, peaked at the 7^th day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-MI group（P= 0.000）, the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups （P = 0.000）. Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups（P= 0.000）. Neovascularization in MCP-1 injected group significantly increased compared with that of other groups（P = 0.000）. Conclusion： Myocardial MCP-1 expression was increased only in the early phase post MI. MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.展开更多
文摘Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC hominghas been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms.
文摘Background Heart failure due to ischemic heart disease is still a major health problem. Myocardium regeneration emerges as a novel therapeutic method for treating myocardial infarction （MI）. However, it is affected by many factors. The present study was aimed to investigate the effect of chemokine stromal cell-derived factor 1 （SDF-1）/CXCL12 on mesenchymal stem cells （MSCs） homing to injured myocardium in a rat myocardial infarction model. Methods A rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with bromodeoxyuridine. The rats were divided into two groups. SDF-1 expression was measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1, 2, 4, 7, 14 and 28 days post operation in the SDF-1 detection group. The rats in the intervention groups were injected with SDF-1, anti-SDF-1 antibody or saline 4 days after myocardial infarction. Then, a total of 5×10^6 cells in 2.5 ml of phosphate-buffered saline were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted on the 3rd day post injection. Cardiac function and blood vessel density were assessed on the 28th day post injection. Results Self-generating SDF-1 expression was increased at the first day post MI, peaked at the 7th day and decreased thereafter while it remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than in the non-MI group （P=0.000）; the MSCs enrichment in the host hearts were more abundant in the SDF-1 injected group than in the anti-SDF-1 antibody and saline injected groups （P = 0.000）. Cardiac function was improved more in the SDF-1 injected group than in the anti-SDF-1 antibody and saline injected groups （P = 0.000）. Neovascularization in the SDF-1 injected group increased significantly compared to the other groups （P= 0.000）. Conclusion My
基金supported by Important National Basic Research Program of China (973 Program, N0.2003CB517103)China Postdoctoral Foundation (No. 20070410129)
文摘Objective:To investigate the effects of panax notoginseng saponins(PNS) on homing of C-kit+ bone mesenchymal stem cells(BMSCs) to the infarction heart.Methods:The acute myocardial infraction(AMI) model was established in 140 Wistar rats,105 model rats survived after operation,and the model rats were randomly divided into five groups,21 rats in each group:Western medicine group mobilized by subcutaneous injection of human granuloctye colony stimulating factor(G-CSF) 50 μg·kg-1·d-1;sham operation group and a model group treated by subcutaneous injection of normal saline 50 μg·kg-1·d-1;Chinese medicine group mobilized by intraperitoneal injection of Xuesaitong(血塞通)(ingredients of PNS) 150 mg·kg-1·d-1;integrative medicine group mobilized by subcutaneous injection of G-CSF 50 μg·kg-1·d-1 and intraperitoneal injection of Xuesaitong 150 mg·kg-1·d-1.Except for the sham-operated group,each group was divided into three sub-groups by three time points of 1 d,7 d and 14 d.G-CSF was injected once a day for 7 d.Xuesaitong was injected once a day until the rats were killed.The flow cytometry was used for detection of C-kit + cells in the peripheral blood in different time points,and immunohistochemical method was used for detection of the changes of C-kit + cell and Ki-67+ cell numbers in the marginal zone of AMI.Results:Twenty-four hours after the operation,C-kit + cells had a slight increase in the model group compared with the sham operation group(P>0.05).The peripheral blood C-kit+ cells in the integrative group increased significantly compared with the other groups on 7 d and 14 d(all P<0.05).Meanwhile the expression of C-kit + cells and Ki-67+ cells in the marginal zone of AMI in the integrative group increased significantly compared with the Chinese medicine group,the western medicine group and the model group on 1 d,7 d and 14 d(all P<0.05),and the cells in the integrative group decreased significantly on 14 d compared with that on 7 d(P<0.05).Conclusion:PNS can cooperate with G-CSF to mobilize C-kit+
基金supported by RC2DE020767 from the National Institute of Dental and Craniofacial Research (NIDCR), the National Institutes of Health (NIH)
文摘A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated？ Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth？ If not, what are the therapeutically viable sources of stem cells for tooth regeneration？ Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration？ How can regenerated teeth be economically competitive with dental implants？ Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide？ This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration： repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes.
文摘牙周病的临床治疗是国际关注的难题,牙周缺损组织的修复面临严峻挑战.传统牙周治疗聚焦炎症控制,虽可阻止或延缓疾病进程,却难以获得牙周再生.从20世纪80年代末开始,引导组织再生（guided tissue regeneration,GTR）、引导骨再生（guided bone regeneration,GBR）等新技术的广泛开展和临床应用,大大提高了牙周病的治疗水平.进入21世纪,干细胞治疗和组织工程研究得到突飞猛进的发展.利用组织工程的原理、技术和方法,有望实现牙周组织的生理性和功能性再生.
基金Supported by the National Natural Science Foundation of China (No.30672770)
文摘Objective： To investigate the effect of Huogu II Formula （活骨 II方 ） with medicinal guide Radix Achyranthis Bidentatae （Ach） on bone marrow stem cells （BMSCs） homing to necrosis area after osteonecrosis of the femoral head （ONFH） frozen by liquid nitrogen in rabbit as well as to explore the mechanism of prevention and treatment for ONFH. Methods： The animal model of ONFH was established by liquid nitrogen frozen on the rabbit left hind leg. Forty-eight Japanese White rabbits were randomly assigned to sham-operated group, model group, Huogu II group, and Huogu II plus Ach group, with 12 rabbits in each. During the course of ONFH animal model establishment, all rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor [rhG-CSF, 30 μg/（kg.day） for continuous 7 days]. Meanwhile, normal saline and decoction of the two formulae were administrated by gavage, respectively. White blood cells （WBC） were counted in peripheral blood before and after injection of rhG-CSF. Materials were drawn on the 2rid and 4th weeks after model built; bone glutamine protein （BGP） and bone morphogenetic protein 2 （BMP2） levels in serum were tested. Histopathologic changes were observed by hematoxylin and eosin （HE） staining. BMP2 mRNA levels were detected with in situ hybridization （iSH） staining. 5-Bromo-2＇-deoxyuridine （BrdU） and stromal cell derived factor 1 （SDF-1） were measured by immunohistochemical assay in femoral head of the left hind leg. Results： Compared with the shamoperated group, the ratio of empty lacuna, serum BGP, and SDF-1 level in the model group increased significantly, and BMP2 in both serum and femoral head decreased significantly. However, in comparison with the model group, the empty lacuna ratio of Huogu II group and Huogu II plus Ach group decreased obviously in addition to the levels of serum BGP and BMP2, and the expressions of BMP2 mRNA, BrdU, and SDF-1 increased significantly. Above changes were particularly obv
文摘Preferential infection and depletion of gut-homing a4β7 CD4＋ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing a4p7 CD4＋ T cells and their functional subsets during the acute stages of HIV-1 infection are less documented. Therefore, we conducted a cohort study to investigate whether acute HIV-1 infection induced abnormalities in gut-homing a4β7 CD4＋ T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing a4β7 CD4＋ T cells in 26 acute HIV-l-infected patients compared with 20 healthy individuals. We found that circulating gut-homing a4β7 CD4＋ T cells were preferentially depleted during acute HIV-1 infection and were positively correlated with absolute CD4＋ T-cell count in blood. Notably, Th17 and Thl cell subsets of gut-homing CD4＋ T cells were also decreased, which resulted in an imbalance of T helper cells （Th 1）-regulatory T cells （Treg） and Treg.Th 17 ratios. Gut-homing Th17 and Thl cells were also positively correlated with the absolute number of total CD4＋ T cells and gut-homing CD4＋ T cells. The gut-homing Treg：Th17 ratio was inversely correlated with the CD4＋ T-cell count. Taken together, the analyses of our acute HIV-1 cohort demonstrate that gut-homing a4β7 CD4＋ T cells and their functional subsets were profoundly depleted during acute HIV-1 infection, which may have resulted in the persistent loss of circulating CD4＋ T cells and an imbalance of Thl-Treg and Treg.Th17 ratios and contribute to HIV-1 disease pathogenesis.
基金supported by the National Key R&D Program of China(No.2022YFA1105603)the Fundamental Research Funds for the Central Universities(No.2022ZFJH003)+3 种基金National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(No.2018ZX09201002-005)the National Natural Science Foundation of China(Nos.82200994 and 81900563)CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045)Shanghai Post-doctoral Excellence Program(No.2022428).
文摘Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis treatment.However,limited sources and poor tissue-homing efficiency limit their clinical capabilities.In this study,we isolated a kind of MSCs from women’s menstrual blood(MenSCs)noninvasively and established a novel MSCs bone marrow-targeted delivery system by utilizing waterin-oil-in-water droplet microfluidics.MenSCs were encapsulated withinβ-cyclodextrin-functionalized alginate microcapsules loaded with zoledronates,which has a high affinity for bone.With this delivery system,MenSCs could be preferentially delivered to the bone marrow tissues via intravenous infusion,and restored bone mass by remodeling the bone marrow niche in situ in ovariectomized mouse models.Moreover,scRNA-seq analysis demonstrated that those MenSCs homed to the bone marrow recruited CD4^(+)FOXP3^(+)natural regulatory T(nT_(reg))cells by secreting CCL28.The recruited nTreg promoted CD8^(+)T cells to secret Wnt family member 10B(WNT10B),activating the Wnt signaling in osteoblasts and thus promoting bone formation in situ in the bone marrow.This study reveals a promising application of MenSCs in postmenopausal osteoporosis treatment and highlights the clinical value of MenSCs by encouraging women to reserve autologous MenSCs before menopause to prevent and alleviate postmenopausal osteoporosis.
文摘Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like "wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed.
基金Supported by Grants from the National Natural Science Foundation of China Project of Guiding Traditional Chinese Medicine Induced Bone Marrow Stem Cell Directional Homing to a Focal Zone for the Treatment of Osteoarthritis(No.81072900)
文摘OBJECTIVE: To investigate the effects of Ermiao Fang(EM) with medical guide Xixin(Herba Asari Mandshurici)(HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis(OA) rats.METHODS: OA rats were induced by arthrectomy and assigned to sham-operated, model, EM, or EM plus HAM groups.All rats were injected with recombinant human granulocyte colony-stimulating factor 30μg·kg-1·d-1for7 days and treated with EMor EM plus HAM at 1.6 or 1.9 g·kg-1·d-1 for 3 or 6 weeks, respectively. Chondrocyte apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Levels of interleukin-1 beta(IL-1β) tumor necrosis factor alpha(TNF-α) nitric oxide(NO), and inducible nitric oxide synthase(iNOS) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay. Matrix metalloproteinases(MMPs)-13,tissue inhibitors of metalloproteinases(TIMPs)-1,Bromodeoxyuridine(BrdU), cluster of differentiation 34(CD34), and stromal cell-derived factor 1(SDF-1) were measured by immunohistochemical assay.RESULTS:The EM and EM plus HAM groups had significantly less cartilage damage and synovium inflammation the model group. Moreover, the EM and EM plus HAM groups had less chondrocyte apoptosis and more proteoglycan and collagen content than the model group.The EM and EMplus HAM groups had obviously higher MMPs-13 and TIMPs-1 expression in the cartilage than the model group. Moreover, the two formula groups had less release of IL-1β, TNF-α, NO, and iNOS than model group. Importantly, the expressions of BrdU, CD34,and SDF-1 in cartilage were significantly higher in the EM and EM plus HAM-Medtreated rats than model group. Notably, the EM plus HAM treatment seemed to have the greatest effects.CONCLUSION: HAM improves the therapeutic effects of EM on OA rats by enhancing BMSC directional homing to the focal zone.
文摘In this paper, we propose the role of mesenchymal stem cells in fracture repair. We investigated the role of bone marrow mesenchymal stem cells in the healing process of fracture and the effect on the migration of endogenous bone marrow mesenchymal stem cells. Experiments show that exogenous bone marrow mesenchymal stem cells implanted in femur fractures in vivo can make endogenous bone marrow mesenchymal stem cells in vitro migration ability and fracture site of nerve growth factor expression increased, which promotes rat fracture healing.
文摘Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missing from the rodent endometrium. Interestingly, CD62L (L-selectin)-deficient BALB/c mice delivered significantly higher numbers of viable offspring than wild type controls via mechanisms yet to be defined. Methods: Nulliparous CD62L-deficient (8-10-week-old, n = 25) or wild type (n = 18) females were mated with 43 age-matched males. Animals were sacrificed at gestational day (GD) 9.5. Tissue samples were analyzed by immunostaining and flow cytometry. Results: Mating wild type and CD62L-deficient BALB/c mice revealed that the increased birth rate was due to the CD62L deficiency in females. Flow cytometric analysis demonstrated significant differences in the number of natural killer (NK) cells present in the uterus of pregnant CD62L- deficient mice compared to controls. Immunohistochemistry confirmed NK cell accumulation at the fetal-maternal interface. Discussion: Uterine NK cells have been shown to peak at GD 8-10 at the fetal-maternal interface. NK cells might regulate mouse fertility rates by facilitating development of the maternal spiral arteries, thereby stimulating the formation of larger vessels that facilitate intrauterine survival, however, their role is not obligate to spiral artery development. Conclusions: Diminished CD62L expression modified immune cell trafficking into the uterus of pregnant mice generating a microenvironment primarily dominated by NK cells resulting in improved embryonic survival rates.
文摘Objective：To investigate the effect of MCP-1 on mesenchymal stem cells（MSCs） homing to injured myocardium in a rat myocardial infarction（MI） model. Methods：Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU. The Rats were divided into two groups. Monocyte chemotactic protein I（MCP-1） expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1, 2, 4, 7, 14 and 28 days post operation in MCP-1 detection group. The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group. Then, a total of 5 × 10^6 cells in 2.5 ml of PBS were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel density were assessed 28 days post injection. Results：Self-generating MCP-1 expression was increased at the first day, peaked at the 7^th day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-MI group（P= 0.000）, the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups （P = 0.000）. Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups（P= 0.000）. Neovascularization in MCP-1 injected group significantly increased compared with that of other groups（P = 0.000）. Conclusion： Myocardial MCP-1 expression was increased only in the early phase post MI. MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.
