The Experts below are selected from a list of 23826 Experts worldwide ranked by ideXlab platform
Jochen Ringe - One of the best experts on this subject based on the ideXlab platform.
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Dose-Dependent Effect of Mesenchymal Stromal Cell Recruiting Chemokine CCL25 on Porcine Tissue-Engineered Healthy and Osteoarthritic Cartilage.
International journal of molecular sciences, 2018Co-Authors: Luise Lüderitz, Michael Sittinger, Tilo Dehne, Jochen RingeAbstract:Thymus-expressed Chemokine (CCL25) is a potent cell attractant for mesenchymal stromal cells, and therefore it is a candidate for in situ cartilage repair approaches focusing on the recruitment of endogenous repair cells. However, the influence of CCL25 on cartilage is unknown. Accordingly, in this study, we investigated the effect of CCL25 on tissue-engineered healthy and osteoarthritic cartilage. Porcine chondrocytes were cultured in a three-dimensional (3D) micromass model that has been proven to mimic key-aspects of human cartilage and osteoarthritic alterations upon stimulation with tumor necrosis factor-α (TNF-α). Micromass cultures were stimulated with CCL25 (0, 0.05, 0.5, 5, 50, 500 nmol/L) alone or in combination with 0.6 nmol/L TNF-α for seven days. Effects were evaluated by life/dead staining, safranin O staining, histomorphometrical analysis of glycosaminoglycans (GAGs), collagen type II (COL2A1) real-time RT-PCR and Porcine Genome Array analysis. 500 nmol/L CCL25 led to a significant reduction of GAGs and COL2A1 expression and induced the expression of matrix metallopeptidases (MMP) 1, MMP3, early growth response protein 1 (EGR1), and superoxide dismutase 2 (SOD2). In concentrations lower than 500 nmol/L, CCL25 seems to be a candidate for in situ cartilage repair therapy approaches.
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Chemokine CCL25 Induces Migration and Extracellular Matrix Production of Anulus Fibrosus-Derived Cells.
International journal of molecular sciences, 2018Co-Authors: Stefan Stich, Jochen Ringe, Anke Möller, Mario Cabraja, Jan Philipp Krüger, Sylvia Hondke, Michaela Endres, Michael SittingerAbstract:Intervertebral disc degeneration is a major source of back pain. For intervertebral disc regeneration after herniation a fast closure of anulus fibrosus (AF) defects is crucial. Here, the use of the C-C motif Chemokine ligand 25 (CCL)25 in comparison to differentiation factors such as transforming growth factor (TGF)β3, bone morphogenetic protein (BMP)2, BMP7, BMP12, and BMP14 (all in concentrations of 10, 50 and 100 ng/mL) was tested in an in vitro micro mass pellet model with isolated and cultivated human AF-cells (n = 3) to induce and enhance AF-matrix formation. The pellets were differentiated (serum-free) with supplementation of the factors. After 28 days all used factors induced proteoglycan production (safranin O staining) and collagen type I production (immunohistochemical staining) in at least one of the tested concentrations. Histomorphometric scoring revealed that TGFβ3 delivered the strongest induction of proteoglycan production in all three concentrations. Furthermore, it was the only factor able to facilitate collagen type II production, even higher than in native tissue samples. CCL25 was also able to induce proteoglycan and collagen type I production comparable to several BMPs. CCL25 could additionally induce migration of AF-cells in a chemotaxis assay and therefore possibly aid in regeneration processes after disc herniation by recruiting AF-cells.
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Delayed release of Chemokine CCL25 with bioresorbable microparticles for mobilization of human mesenchymal stem cells.
Acta biomaterialia, 2018Co-Authors: Kristin Fröhlich, Michael Sittinger, Jan Eucker, David Hartzke, Franziska Schmidt, Aleksander Gurlo, Jochen RingeAbstract:Abstract Chemokines are guiding cues for directional trafficking of mesenchymal stem cells (MSC) upon injury and local Chemokine delivery at injury sites is an up-to-date strategy to potentiate and prolong recruitment of MSC. In this study we present the Chemokine CCL25, also referred to as thymus-expressed Chemokine, to mobilize human MSC along positive but not along negative gradients. We hence proceeded to design a biodegradable and injectable release device for CCL25 on the basis of poly(lactic-co-glycolic acid) (PLGA). The conducted studies had the objective to optimize PLGA microparticle fabrication by varying selected formulation parameters, such as polymer type, microparticle size and interior phase composition. We found that microparticles of DV,50∼75 µm and fabricated using end-capped polymers, BSA as carrier protein and vortex mixing to produce the primary emulsion yielded high Chemokine loading and delayed CCL25 release. To determine bioactivity, we investigated CCL25 released during the microparticle erosion phase and showed that deacidification of the release medium was required to induce significant MSC mobilization. The designed PLGA microparticles represent an effective and convenient off-the-shelf delivery tool for the delayed release of CCL25. However, continuative in vivo proof-of-concept studies are required to demonstrate enhanced recruitment of MSC and/or therapeutical effects in response to CCL25 release microparticles. Statement of Significance With the discovery of Chemokines, particularly CXCL12, as stimulators of stem cell migration, the development of devices that release CXCL12 has proceeded quickly in the last few years. In this manuscript we introduce CCL25 as Chemokine to induce mobilization of human MSC. This study proceeds to demonstrate how selection of key formulation parameters of CCL25 loading into PLGA microparticles exerts considerable influence on CCL25 release. This is important for a broad range of efforts in in situ tissue engineering where the candidate Chemokine and the delivery device need to be selected carefully. The use of such a cell-free CCL25 release device may provide a new therapeutic option in regenerative medicine.
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mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine receptor ccr9 and chemotactically migrate toward CCL25 or serum
Stem Cell Research & Therapy, 2013Co-Authors: Mujib Ullah, Michael Sittinger, Jan Eucker, Jochen RingeAbstract:Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells. MSC-derived chondrogenically differentiated cells were characterized for morphology, histology, immunohistochemistry, quantitative polymerase chain reaction (qPCR), surface profile, and serum- or CCL25-mediated cell migration. Additionally, the Chemokine receptor, CCR9, was examined in different states of MSCs. The chondrogenic differentiated state of MSCs was positive for collagen type II and Alcian blue staining, and showed significantly upregulated expression of COL2A1 and SOX9, and downregulated expression of CD44, CD73, CD90, CD105 and CD166, in contrast to the undifferentiated and dedifferentiated states of MSCs. For the chondrogenic differentiated, undifferentiated, and dedifferentiated states of MSCs, the serum-mediated chemotaxis was in a percentage ratio of 33%:84%:85%, and CCL25-mediated chemotaxis was in percentage ratio of 12%:14%:13%, respectively. On the protein level, CCR9, receptor of CCL25, was expressed in the form of extracellular and intracellular domains. On the gene level, qPCR confirmed the expression of CCR9 in different states of MSCs. CCL25 is an effective cue to guide migration in a directional way. In CCL25-mediated chemotaxis, the cell-migration rate was almost the same for different states of MSCs. In serum-mediated chemotaxis, the cell-migration rate of chondrogenically differentiated cells was significantly lower than that in undifferentiated or dedifferentiated cells. Current knowledge of the surface CD profile and cell migration could be beneficial for regenerative cellular therapies.
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Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine receptor CCR9 and chemotactically migrate toward CCL25 or serum.
Stem cell research & therapy, 2013Co-Authors: Mujib Ullah, Michael Sittinger, Jan Eucker, Jochen RingeAbstract:Introduction Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells.
Michael Sittinger - One of the best experts on this subject based on the ideXlab platform.
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Dose-Dependent Effect of Mesenchymal Stromal Cell Recruiting Chemokine CCL25 on Porcine Tissue-Engineered Healthy and Osteoarthritic Cartilage.
International journal of molecular sciences, 2018Co-Authors: Luise Lüderitz, Michael Sittinger, Tilo Dehne, Jochen RingeAbstract:Thymus-expressed Chemokine (CCL25) is a potent cell attractant for mesenchymal stromal cells, and therefore it is a candidate for in situ cartilage repair approaches focusing on the recruitment of endogenous repair cells. However, the influence of CCL25 on cartilage is unknown. Accordingly, in this study, we investigated the effect of CCL25 on tissue-engineered healthy and osteoarthritic cartilage. Porcine chondrocytes were cultured in a three-dimensional (3D) micromass model that has been proven to mimic key-aspects of human cartilage and osteoarthritic alterations upon stimulation with tumor necrosis factor-α (TNF-α). Micromass cultures were stimulated with CCL25 (0, 0.05, 0.5, 5, 50, 500 nmol/L) alone or in combination with 0.6 nmol/L TNF-α for seven days. Effects were evaluated by life/dead staining, safranin O staining, histomorphometrical analysis of glycosaminoglycans (GAGs), collagen type II (COL2A1) real-time RT-PCR and Porcine Genome Array analysis. 500 nmol/L CCL25 led to a significant reduction of GAGs and COL2A1 expression and induced the expression of matrix metallopeptidases (MMP) 1, MMP3, early growth response protein 1 (EGR1), and superoxide dismutase 2 (SOD2). In concentrations lower than 500 nmol/L, CCL25 seems to be a candidate for in situ cartilage repair therapy approaches.
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Chemokine CCL25 Induces Migration and Extracellular Matrix Production of Anulus Fibrosus-Derived Cells.
International journal of molecular sciences, 2018Co-Authors: Stefan Stich, Jochen Ringe, Anke Möller, Mario Cabraja, Jan Philipp Krüger, Sylvia Hondke, Michaela Endres, Michael SittingerAbstract:Intervertebral disc degeneration is a major source of back pain. For intervertebral disc regeneration after herniation a fast closure of anulus fibrosus (AF) defects is crucial. Here, the use of the C-C motif Chemokine ligand 25 (CCL)25 in comparison to differentiation factors such as transforming growth factor (TGF)β3, bone morphogenetic protein (BMP)2, BMP7, BMP12, and BMP14 (all in concentrations of 10, 50 and 100 ng/mL) was tested in an in vitro micro mass pellet model with isolated and cultivated human AF-cells (n = 3) to induce and enhance AF-matrix formation. The pellets were differentiated (serum-free) with supplementation of the factors. After 28 days all used factors induced proteoglycan production (safranin O staining) and collagen type I production (immunohistochemical staining) in at least one of the tested concentrations. Histomorphometric scoring revealed that TGFβ3 delivered the strongest induction of proteoglycan production in all three concentrations. Furthermore, it was the only factor able to facilitate collagen type II production, even higher than in native tissue samples. CCL25 was also able to induce proteoglycan and collagen type I production comparable to several BMPs. CCL25 could additionally induce migration of AF-cells in a chemotaxis assay and therefore possibly aid in regeneration processes after disc herniation by recruiting AF-cells.
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Delayed release of Chemokine CCL25 with bioresorbable microparticles for mobilization of human mesenchymal stem cells.
Acta biomaterialia, 2018Co-Authors: Kristin Fröhlich, Michael Sittinger, Jan Eucker, David Hartzke, Franziska Schmidt, Aleksander Gurlo, Jochen RingeAbstract:Abstract Chemokines are guiding cues for directional trafficking of mesenchymal stem cells (MSC) upon injury and local Chemokine delivery at injury sites is an up-to-date strategy to potentiate and prolong recruitment of MSC. In this study we present the Chemokine CCL25, also referred to as thymus-expressed Chemokine, to mobilize human MSC along positive but not along negative gradients. We hence proceeded to design a biodegradable and injectable release device for CCL25 on the basis of poly(lactic-co-glycolic acid) (PLGA). The conducted studies had the objective to optimize PLGA microparticle fabrication by varying selected formulation parameters, such as polymer type, microparticle size and interior phase composition. We found that microparticles of DV,50∼75 µm and fabricated using end-capped polymers, BSA as carrier protein and vortex mixing to produce the primary emulsion yielded high Chemokine loading and delayed CCL25 release. To determine bioactivity, we investigated CCL25 released during the microparticle erosion phase and showed that deacidification of the release medium was required to induce significant MSC mobilization. The designed PLGA microparticles represent an effective and convenient off-the-shelf delivery tool for the delayed release of CCL25. However, continuative in vivo proof-of-concept studies are required to demonstrate enhanced recruitment of MSC and/or therapeutical effects in response to CCL25 release microparticles. Statement of Significance With the discovery of Chemokines, particularly CXCL12, as stimulators of stem cell migration, the development of devices that release CXCL12 has proceeded quickly in the last few years. In this manuscript we introduce CCL25 as Chemokine to induce mobilization of human MSC. This study proceeds to demonstrate how selection of key formulation parameters of CCL25 loading into PLGA microparticles exerts considerable influence on CCL25 release. This is important for a broad range of efforts in in situ tissue engineering where the candidate Chemokine and the delivery device need to be selected carefully. The use of such a cell-free CCL25 release device may provide a new therapeutic option in regenerative medicine.
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mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine receptor ccr9 and chemotactically migrate toward CCL25 or serum
Stem Cell Research & Therapy, 2013Co-Authors: Mujib Ullah, Michael Sittinger, Jan Eucker, Jochen RingeAbstract:Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells. MSC-derived chondrogenically differentiated cells were characterized for morphology, histology, immunohistochemistry, quantitative polymerase chain reaction (qPCR), surface profile, and serum- or CCL25-mediated cell migration. Additionally, the Chemokine receptor, CCR9, was examined in different states of MSCs. The chondrogenic differentiated state of MSCs was positive for collagen type II and Alcian blue staining, and showed significantly upregulated expression of COL2A1 and SOX9, and downregulated expression of CD44, CD73, CD90, CD105 and CD166, in contrast to the undifferentiated and dedifferentiated states of MSCs. For the chondrogenic differentiated, undifferentiated, and dedifferentiated states of MSCs, the serum-mediated chemotaxis was in a percentage ratio of 33%:84%:85%, and CCL25-mediated chemotaxis was in percentage ratio of 12%:14%:13%, respectively. On the protein level, CCR9, receptor of CCL25, was expressed in the form of extracellular and intracellular domains. On the gene level, qPCR confirmed the expression of CCR9 in different states of MSCs. CCL25 is an effective cue to guide migration in a directional way. In CCL25-mediated chemotaxis, the cell-migration rate was almost the same for different states of MSCs. In serum-mediated chemotaxis, the cell-migration rate of chondrogenically differentiated cells was significantly lower than that in undifferentiated or dedifferentiated cells. Current knowledge of the surface CD profile and cell migration could be beneficial for regenerative cellular therapies.
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Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine receptor CCR9 and chemotactically migrate toward CCL25 or serum.
Stem cell research & therapy, 2013Co-Authors: Mujib Ullah, Michael Sittinger, Jan Eucker, Jochen RingeAbstract:Introduction Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells.
Marc-andré Wurbel - One of the best experts on this subject based on the ideXlab platform.
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CCL25 ccr9 interactions are not essential for colitis development but are required for innate immune cell protection from chronic experimental murine colitis
Inflammatory Bowel Diseases, 2014Co-Authors: Marc-andré Wurbel, Mouna Ibourk, Michael Pardo, Maria G. Mcintire, Dominique Coco, Raif S. Geha, Severine Le Bras, Edda FiebigerAbstract:BACKGROUND The Chemokine CCL25, and its receptor CCR9, constitute a unique Chemokine/receptor pair, which regulates trafficking of T lymphocytes to the small intestine under physiological conditions and is an attractive target for small bowel Crohn's disease drug development. We have previously shown that CCL25/CCR9 interactions regulate the recovery from acute dextran sulfate sodium-induced colonic inflammation. In this study, we explored whether these interactions also regulate chronic colitis development in 2 independent murine models of experimental colitis. METHODS Histological flow cytometry and qPCR analyses were performed to evaluate the role of CL25 and CCR9 in chronic colonic inflammation induced by serial exposures to dextran sulfate sodium salts or by adoptive transfer of CD45RB(hi) CD4(+) T cell into lymphopenic mice devoid of CCL25/CCR9 interactions. RESULTS Chronic dextran sulfate sodium exposure results in exacerbated colitis in mice deficient for either CCR9 or CCL25 when compared with wild-type control mice. Although CCR9-deficient T cells traffic to the colon and induce severe colitis similar to wild-type T cells in the CD45RB transfer model, naive wild-type T cells induce more severe disease in recipient animals devoid of CCL25 expression. CONCLUSIONS CCL25/CCR9 interactions are required for modulating protection against large intestinal inflammation in 2 models of chronic colitis. These data may have implications for the potential effects of disrupting CCL25/CCR9 interactions in humans in the setting of intestinal disorders including inflammatory bowel disease.
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the Chemokine receptor ccr9 is required for the t cell mediated regulation of chronic ileitis in mice
Gastroenterology, 2011Co-Authors: Joshua D Wermers, Marc-andré Wurbel, Eoin N Mcnamee, Paul Jedlicka, Jesus Rivera NievesAbstract:Background & Aims A balance between effector and regulatory T-cell (Treg) responses is required to maintain intestinal homeostasis. To regulate immunity, T cells migrate to the intestine using a combination of adhesion molecules and Chemokine receptors. However, it is not known whether the migration pathways of effector cells and Tregs are distinct or shared. We sought to determine whether interaction between the Chemokine receptor 9 (CCR9) and its ligand, Chemokine ligand 25 (CCL25), allows effectors or Tregs to localize to chronically inflamed small intestine. Methods By using a mouse model that develops Crohn's-like ileitis (tumor necrosis factor Δadenosine uracyl-rich element [TNFΔARE] mice) we examined the role of CCL25–CCR9 interactions for effector and Treg traffic using flow cytometry, quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, immunoneutralization, and proliferation analyses. Results In TNFΔARE mice, expression of CCL25 and the frequency of CCR9-expressing lymphocytes increased during late-stage disease. In the absence of CCR9, TNFΔARE mice developed exacerbated disease, compared with their CCR9-sufficient counterparts, which coincided with a deficiency of CD4 + /CD25 + /forkhead box P3 + and CD8 + /CD103 + Tregs within the intestinal lamina propria and mesenteric lymph nodes. Furthermore, the CD8 + /CCR9 + subset decreased the proliferation of CD4 + T cells in vitro. Administration of a monoclonal antibody against CCR9 to TNFΔARE mice exacerbated ileitis in vivo, confirming the regulatory role of CD8 + /CCR9 + cells. Conclusions Signaling of the Chemokine CCL25 through its receptor CCR9 induces Tregs to migrate to the intestine. These findings raise concerns about the development of reagents to disrupt this pathway for the treatment of patients with Crohn's disease.
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Impaired accumulation of antigen-specific CD8 lymphocytes in Chemokine CCL25-deficient intestinal epithelium and lamina propria.
Journal of immunology (Baltimore Md. : 1950), 2007Co-Authors: Marc-andré Wurbel, Marie Malissen, Delphine Guy-grand, Bernard Malissen, James J. CampbellAbstract:CCL25 and CCR9 constitute a Chemokine/receptor pair involved in T cell development and in gut-associated immune responses. In this study, we generated CCL25−/− mice to answer questions that could not be addressed with existing CCR9−/− mice. Similar phenotypes were observed for both CCL25−/− and CCR9−/− mice, consistent with the notion that CCL25 and CCR9 interact with each other exclusively. We assessed the requirement for CCL25 in generating CCR9high CD8 intestinal memory-phenotype T cells and the subsequent accumulation of these cells within effector sites. TCR-transgenic naive CD8 T cells were transferred into wild-type or CCL25-deficient hosts. Oral sensitization with Ag allowed these naive donor cells to efficiently differentiate into CCR9high memory-phenotype cells within the mesenteric lymph nodes of wild-type hosts. This differentiation event occurred with equal efficiency in the MLN of CCL25-deficient hosts, demonstrating that CCL25 is not required to induce the CCR9high memory phenotype in vivo. However, we found that CCL25 deficiency severely impaired the Ag-dependent accumulation of donor-derived CD8 T cells within both lamina propria and epithelium of the small intestine. Thus, although CCL25 is not necessary for generating memory-phenotype CD8 T cells with “gut-homing” properties, this Chemokine is indispensable for their trafficking to the small intestine.
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Chemokine Receptor CCR9 Contributes to the Localization of Plasma Cells to the Small Intestine
The Journal of experimental medicine, 2004Co-Authors: Oliver Pabst, Marc-andré Wurbel, Bernard Malissen, Lars Ohl, Meike Wendland, Elisabeth Kremmer, Reinhold FörsterAbstract:Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The Chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.
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Mice lacking the CCR9 CC-Chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor γδ+ gut intraepithelial lymphocytes
Blood, 2001Co-Authors: Marc-andré Wurbel, Marie Malissen, Delphine Guy-grand, Eric Meffre, Michel C. Nussenzweig, Mireille Richelme, Alice Carrier, Bernard MalissenAbstract:CC Chemokine receptor (CCR) 9, the receptor for the CC-Chemokine CCL25/thymus-expressed Chemokine (TECK), is mainly expressed by thymocytes and by intraepithelial (IEL) and lamina propria lymphocytes of the small intestine. To study the biologic role of CCR9, a mouse strain was generated in which the CCR9 gene was deleted. In spite of the high level of CCR9 found in double- and single-positive thymocytes and of the expression of its corresponding ligand on thymic stromal cells, CCR9 deletion had no major effect on intrathymic T-cell development. It was noted that there was only a one-day lag in the appearance of double-positive cells during fetal ontogeny in CCR9−/− thymi. When tested in chemotaxis assay, thymocytes isolated from CCR9−/− mice failed to respond to TECK/CCL25. Taken together, these results suggest that in thymocytes, CCR9 is the only physiologic receptor for TECK/CCL25, and that it is dispensable for proper T-cell development. Bone marrow pre-pro–B cells migrate in response to TECK/CCL25, but more mature B cells do not. Consistent with this observation, it was shown that there are fewer pre-pro–B cells in CCR9−/−mice than in wild-type mice. However, this diminution does not appear to have a detectable effect on the generation of a normal complement of mature B cells. Finally, it was shown that in the small intestine of CCR9-deficient mice, the intraepithelial T-cell–to–epithelial cell ratio is decreased, an observation that can be accounted for by a marked diminution of the T-cell receptor γδ+ compartment.
Jan Eucker - One of the best experts on this subject based on the ideXlab platform.
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Delayed release of Chemokine CCL25 with bioresorbable microparticles for mobilization of human mesenchymal stem cells.
Acta biomaterialia, 2018Co-Authors: Kristin Fröhlich, Michael Sittinger, Jan Eucker, David Hartzke, Franziska Schmidt, Aleksander Gurlo, Jochen RingeAbstract:Abstract Chemokines are guiding cues for directional trafficking of mesenchymal stem cells (MSC) upon injury and local Chemokine delivery at injury sites is an up-to-date strategy to potentiate and prolong recruitment of MSC. In this study we present the Chemokine CCL25, also referred to as thymus-expressed Chemokine, to mobilize human MSC along positive but not along negative gradients. We hence proceeded to design a biodegradable and injectable release device for CCL25 on the basis of poly(lactic-co-glycolic acid) (PLGA). The conducted studies had the objective to optimize PLGA microparticle fabrication by varying selected formulation parameters, such as polymer type, microparticle size and interior phase composition. We found that microparticles of DV,50∼75 µm and fabricated using end-capped polymers, BSA as carrier protein and vortex mixing to produce the primary emulsion yielded high Chemokine loading and delayed CCL25 release. To determine bioactivity, we investigated CCL25 released during the microparticle erosion phase and showed that deacidification of the release medium was required to induce significant MSC mobilization. The designed PLGA microparticles represent an effective and convenient off-the-shelf delivery tool for the delayed release of CCL25. However, continuative in vivo proof-of-concept studies are required to demonstrate enhanced recruitment of MSC and/or therapeutical effects in response to CCL25 release microparticles. Statement of Significance With the discovery of Chemokines, particularly CXCL12, as stimulators of stem cell migration, the development of devices that release CXCL12 has proceeded quickly in the last few years. In this manuscript we introduce CCL25 as Chemokine to induce mobilization of human MSC. This study proceeds to demonstrate how selection of key formulation parameters of CCL25 loading into PLGA microparticles exerts considerable influence on CCL25 release. This is important for a broad range of efforts in in situ tissue engineering where the candidate Chemokine and the delivery device need to be selected carefully. The use of such a cell-free CCL25 release device may provide a new therapeutic option in regenerative medicine.
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mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine receptor ccr9 and chemotactically migrate toward CCL25 or serum
Stem Cell Research & Therapy, 2013Co-Authors: Mujib Ullah, Michael Sittinger, Jan Eucker, Jochen RingeAbstract:Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells. MSC-derived chondrogenically differentiated cells were characterized for morphology, histology, immunohistochemistry, quantitative polymerase chain reaction (qPCR), surface profile, and serum- or CCL25-mediated cell migration. Additionally, the Chemokine receptor, CCR9, was examined in different states of MSCs. The chondrogenic differentiated state of MSCs was positive for collagen type II and Alcian blue staining, and showed significantly upregulated expression of COL2A1 and SOX9, and downregulated expression of CD44, CD73, CD90, CD105 and CD166, in contrast to the undifferentiated and dedifferentiated states of MSCs. For the chondrogenic differentiated, undifferentiated, and dedifferentiated states of MSCs, the serum-mediated chemotaxis was in a percentage ratio of 33%:84%:85%, and CCL25-mediated chemotaxis was in percentage ratio of 12%:14%:13%, respectively. On the protein level, CCR9, receptor of CCL25, was expressed in the form of extracellular and intracellular domains. On the gene level, qPCR confirmed the expression of CCR9 in different states of MSCs. CCL25 is an effective cue to guide migration in a directional way. In CCL25-mediated chemotaxis, the cell-migration rate was almost the same for different states of MSCs. In serum-mediated chemotaxis, the cell-migration rate of chondrogenically differentiated cells was significantly lower than that in undifferentiated or dedifferentiated cells. Current knowledge of the surface CD profile and cell migration could be beneficial for regenerative cellular therapies.
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Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine receptor CCR9 and chemotactically migrate toward CCL25 or serum.
Stem cell research & therapy, 2013Co-Authors: Mujib Ullah, Michael Sittinger, Jan Eucker, Jochen RingeAbstract:Introduction Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells.
Mujib Ullah - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine receptor ccr9 and chemotactically migrate toward CCL25 or serum
Stem Cell Research & Therapy, 2013Co-Authors: Mujib Ullah, Michael Sittinger, Jan Eucker, Jochen RingeAbstract:Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells. MSC-derived chondrogenically differentiated cells were characterized for morphology, histology, immunohistochemistry, quantitative polymerase chain reaction (qPCR), surface profile, and serum- or CCL25-mediated cell migration. Additionally, the Chemokine receptor, CCR9, was examined in different states of MSCs. The chondrogenic differentiated state of MSCs was positive for collagen type II and Alcian blue staining, and showed significantly upregulated expression of COL2A1 and SOX9, and downregulated expression of CD44, CD73, CD90, CD105 and CD166, in contrast to the undifferentiated and dedifferentiated states of MSCs. For the chondrogenic differentiated, undifferentiated, and dedifferentiated states of MSCs, the serum-mediated chemotaxis was in a percentage ratio of 33%:84%:85%, and CCL25-mediated chemotaxis was in percentage ratio of 12%:14%:13%, respectively. On the protein level, CCR9, receptor of CCL25, was expressed in the form of extracellular and intracellular domains. On the gene level, qPCR confirmed the expression of CCR9 in different states of MSCs. CCL25 is an effective cue to guide migration in a directional way. In CCL25-mediated chemotaxis, the cell-migration rate was almost the same for different states of MSCs. In serum-mediated chemotaxis, the cell-migration rate of chondrogenically differentiated cells was significantly lower than that in undifferentiated or dedifferentiated cells. Current knowledge of the surface CD profile and cell migration could be beneficial for regenerative cellular therapies.
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Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine receptor CCR9 and chemotactically migrate toward CCL25 or serum.
Stem cell research & therapy, 2013Co-Authors: Mujib Ullah, Michael Sittinger, Jan Eucker, Jochen RingeAbstract:Introduction Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells.