Dataset Information

PTH/SDF-1? cotherapy induces CD90+CD34- stromal cells migration and promotes tissue regeneration in a rat periodontal defect model.

ABSTRACT: Stromal cell-derived factor-1? (SDF-1?) is a key stem cell homing factor that is crucial for recruitment of stem cells to many diseased organs. However, the therapeutic activity of SDF-1? is potentially limited by N-terminal cleavage at position-2 proline by a cell surface protein CD26/dipeptidyl peptidase-IV (DPP-IV). Parathyroid hormone (PTH) is a DPP-IV inhibitor and has been suggested as a promising agent for periodontal tissue repair. The purpose of this study was to explore the effects of a cell-free system comprising SDF-1? and scaffold plus PTH systemic application on periodontal tissue regeneration in vivo. The results showed that PTH/SDF-1? cotherapy improved the quantity of regenerated bone and resulted in better organization of ligament interface. We further investigated the possible mechanisms, and found that PTH/SDF-1? cotherapy enhanced CD90+CD34- stromal cells migration in vivo, increased the number of CXCR4?+?cells in periodontal defects, induced early bone osteoclastogenesis and enhanced the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and collagen I (Col I) in newly formed bone tissue. In conclusion, this cell-free tissue engineering system with local administration of SDF-1? and systemic application of PTH could be employed to induce CD90+CD34- stromal cells recruitment and promote periodontal tissue regeneration.

SUBMITTER: Wang F

PROVIDER: S-EPMC4969616 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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PTH/SDF-1α cotherapy induces CD90+CD34- stromal cells migration and promotes tissue regeneration in a rat periodontal defect model.

Wang Fang F Du Lingqian L Ge Shaohua S

Scientific reports 20160802

Stromal cell-derived factor-1α (SDF-1α) is a key stem cell homing factor that is crucial for recruitment of stem cells to many diseased organs. However, the therapeutic activity of SDF-1α is potentially limited by N-terminal cleavage at position-2 proline by a cell surface protein CD26/dipeptidyl peptidase-IV (DPP-IV). Parathyroid hormone (PTH) is a DPP-IV inhibitor and has been suggested as a promising agent for periodontal tissue repair. The purpose of this study was to explore the effects of ...[more]

PMID: 27480134

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Project description:BackgroundThe control of endothelial progenitor cells (CD133+/CD34+ EPCs) migrating from bone marrow to peripheral blood is not completely understood. Emerging evidence suggests that stromal cell-derived factor-1α (SDF-1α) mediates egression of EPCs from bone marrow, while the hypoxia inducible factor (HIF) transcriptional system regulates SDF-1α expression. Our study aimed to investigate the time course of circulating CD133+/CD34+ EPCs and its correlation with the expression of HIF-1α protein and SDF-1α in postoperative laparoscopic abdominal septic patients.MethodsPostoperative patients were divided in control (C group) and septic group (S group) operated immediately after the diagnosis of sepsis/septic shock. Blood samples were collected at baseline (0), 1, 3 and 7 postoperative days for CD133+/CD34+ EPCs count expressing or not the HIF-1α and SDF-1α analysis.ResultsThirty-two patients in S group and 39 in C group were analyzed. In C group CD133+/CD34+ EPCs count remained stable throughout the study period, increasing on day 7 (173 [0-421] /μl vs baseline: P = 0.04; vs day 1: P = 0.002). In S group CD133+/CD34+ EPCs count levels were higher on day 3 (vs day 1: P = 0.006 and day 7: P = 0.026). HIF-1α expressing CD133+/CD34+ EPCs count decreased on day 1 as compared with the other days in C group (day 0 vs 1: P = 0.003, days 3 and 7 vs 1: P = 0.008), while it was 321 [0-1418] /μl on day 3 (vs day 1; P = 0.004), and 400 [0-587] /μl on day 7 in S group. SDF-1α levels were higher not only on baseline but also on postoperative day 1 in S vs C group (219 [124-337] pg/ml vs 35 [27-325] pg/ml, respectively; P = 0.01).ConclusionOur results indicate that sepsis in abdominal laparoscopic patients might constitute an additional trigger of the EPCs mobilization as compared with non-septic surgical patients. A larger mobilization of CD133+/CD34+ EPCs, preceded by enhanced plasmatic SDF-1α, occurs in septic surgical patients regardless of HIF-1α expression therein.Trial registrationClinicalTrials.gov no. NCT02589535 . Registered 28 October 2015.

Project description:BackgroundOne of the most frequent disorders is liver fibrosis. An improved understanding of the different events during the process of liver fibrosis & its reversibility could be helpful in its staging and in finding potential therapeutic agents.AimThe goal of this research was to evaluate the relationship among CD34 + HPSCs, SDF-1α, and CXCR4 receptor expression with the percentage of the area of hepatic fibrosis.Materials and methodsThirty-six male Sprague-Dawley rats were separated into the control group, liver injury group & spontaneous reversion group. The liver injury was induced by using 2 ml/kg CCl4 twice a week. Flow cytometric examination of CD34 + cells in the blood & liver was performed. Bone marrow & liver samples were taken for evaluation of the SDF-1α mRNA by PCR. Liver specimens were stained for histopathological and CXCR4 immuno-expression evaluation.ResultsIn the liver injury group, the hepatic enzymes, fibrosis area percentage, CXCR4 receptor expression in the liver, CD34 + cells in the blood and bone marrow & the level SDF-1α in the liver and its concentration gradient were statistically significantly elevated with the progression of the liver fibrosis. On the contrary, SDF-1α in the bone marrow was statistically significantly reduced with the development of liver fibrosis. During the spontaneous reversion group, all the studied parameters apart from SDF-1α in the bone marrow were statistically substantially decreased compared with the liver injury group. We found a statistically substantial positive correlation between fibrosis area and all of the following: liver enzymes, CXCR4 receptor expression in the liver, CD34 + cells in the blood and liver, and SDF- 1α in the liver and its concentration gradient. In conclusion, in CCl4 rat model, the fibrosis area is significantly correlated with many parameters in the blood, bone marrow, and liver, which can be used during the process of follow-up during the therapeutic interventions.

Project description:Recent studies have noted the tumor-stroma interaction as an integral part of tumor growth and spread as well as novel avenues for effective treatment. However, the details by which tumor and stroma cells communicate remain poorly understood. Here we show that the migration speed of the non-small-cell lung tumor cell line H838 is significantly increased under the influence of human pulmonary endothelial cells, HPAEC, in a transfilter co-culture system. To elucidate the effect of cell communication on the increased tumor cell migration, we record the H838 transcriptome response after the induction of migration in a hetero- and homogenous co-culture conditions. Gene Set enrichment analysis indicates a migration response of H838 in heterogenous co-culture system. Moreover, computationally transcription factor analysis relates the specific gene expression response to the cytokine-induced up-stream receptor activity and subsequently linking these factors to the upstream receptors via shortest paths across a directed protein-protein interaction network. This analysis predicted TNF- and SDF-1 signaling as well as multiple receptors upstream of Stat3 as putative mediators of the transcriptome response. To close the signaling information path from transcription factors to the possible receptor activation, we determine secretome quantification using a cytokine array. The latter revealed the predicted TNFa, SDF-1a signaling molecules as well as other known migration cytokines, like IL8 and IL6, as possible candidates for increased migration. Addition through the recombinant proteins or respected inhibitions reveal TNFa as well as SDF-1a as an immediate and early-late secreted factors that cause the increase in H838 migration. Interestingly, both factors were not regulated on the gene level of the H838 in heterogenous co-culture conditions, consequential HPAEC produce TNFa and SDF1a as shown by qPCR technique. Concluding, our combined computational and experimental approach revealed a holistic overview on the migration enhancement of lung tumor cells due to endothelial derived factors. Increase in migration is caused by an early TNFa induced inflammation response followed by a SDF-1a activity to sustaining the phenotype of migration. This tumor-endothelial-communication give a new insight for tumor migration.

Dataset Information

PTH/SDF-1? cotherapy induces CD90+CD34- stromal cells migration and promotes tissue regeneration in a rat periodontal defect model.

Publications

PTH/SDF-1α cotherapy induces CD90+CD34- stromal cells migration and promotes tissue regeneration in a rat periodontal defect model.

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