Papers by Gundula Schulze-tanzil
Bone & Joint Research
Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The m... more Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide ...
International Journal of Molecular Sciences
The aim of this Special Issue is to summarize the latest developments in tendon/ligament research... more The aim of this Special Issue is to summarize the latest developments in tendon/ligament research and tissue engineering (TE), providing helpful approaches for future tendon/ligament reconstruction (Figure 1) [...]
Background Anti-inflammatory nanoparticular compounds could represent a strategy to diminish oste... more Background Anti-inflammatory nanoparticular compounds could represent a strategy to diminish osteoarthritis (OA) progression. The present study was undertaken to prove the uptake of nanoparticular dendritic polyglycerol sulfates (dPGS) by rat-derived articular chondrocytes and to answer the question of whether dPGS could modulate knee joint cartilage degradation in a rat OA model and whether complications could arise. Methods dPGS uptake and cytotoxicity was assessed in cultured primary rat-derived articular chondrocytes. Subsequently, OA was induced in the right knee joints of 12 male Wistar rats by medial collateral ligament and meniscus transection. Unoperated left knees remained as controls. Six weeks post surgery six rats were either treated daily (14 days) with 30 mg/kg dPGS (s.c.) or a similar volume of physiological saline. Animals were analyzed clinically for gait alterations. Explanted knee joints were studied histologically using OA scores according to Mankin (1971), Glas...
Fragestellung: Zellsphäroide können zur Besiedlung von Scaffolds genutzt werden, da die Zellen fä... more Fragestellung: Zellsphäroide können zur Besiedlung von Scaffolds genutzt werden, da die Zellen fähig sind, ihren Verband wieder zu verlassen und auf die angebotene Matrix auszuwachsen. Ligament Zellen könnten bei der Anzucht in hoher Dichte als dreidimensionale Sphäroidkultur[for full text, please go to the a.m. URL]
Einleitung: Vor einigen Jahren kamen nicht pharmakologische Nasensprays zur antisymptomatischen b... more Einleitung: Vor einigen Jahren kamen nicht pharmakologische Nasensprays zur antisymptomatischen bei allergischer Rhinitis auf den Markt. Wenn der nasoseptale Knorpel freiliegt, wie zum Beispiel bei einer Nasenseptumperforation, kommt es zu einer direkten Exposition des Knorpels gegenüber dem Nasenspray. Deshalb war es das Ziel unserer Studie den Einfluss eines thixotropen und eines liposomalen Nasensprays auf die Vitalität der nasoseptalen Chondrozyten zu untersuchen. Methodik: Humane Chondrozyten und humane und porcine Knorpelstanzen des Nasenseptums waren für 4–24 Stunden beiden Nasensprays ausgesetzt. Mit den unbehandelten Kontrollen wurden die Zellvitalität und das Gen- und Proteinexpressionsprofil (Kollagen Typ I und II, SOX9 und Metalloproteinasen) durch die RTD-PCR und Immunhistochemie verglichen. Ergebnisse: Die Applikation des liposomalen Nasensprays aber nicht des thixotropischen Nasensprays auf die kultivierte Knorpelstanze und auf die kultivierten Chondrozyten führte zu ...
Objectives: Osteoarthritis (OA) is the most common degenerative disease of the musculoskeletal sy... more Objectives: Osteoarthritis (OA) is the most common degenerative disease of the musculoskeletal system. Sufficient therapy of degenerated cartilage is not possible, since mature cartilage has a limited capacity for intrinsic repair. OA is a progressive disease with increasing functional impairment of[for full text, please go to the a.m. URL]
Fragestellung: Die Synovialmembran spielt in der Pathogenese der Arthrose eine aktive Rolle. Von ... more Fragestellung: Die Synovialmembran spielt in der Pathogenese der Arthrose eine aktive Rolle. Von verschiedenen Zelltypen im arthrotischen Gelenk freigesetzte proinflammatorische Mediatoren wie Tumornekrosefaktor α (TNF α ) könnten die Synthese zusätzlicher proinflammatorischer[for full text, please go to the a.m. URL]
HS-induced risk for immunosuppression was confirmed by changes of total lymphocytes in murine per... more HS-induced risk for immunosuppression was confirmed by changes of total lymphocytes in murine peripheral blood. Peripheral blood from HS, sham, and control animals was obtained as described in Materials and methods and analyzed by differential hemogram. *< 0.05 as determined by analysis of variance (with Bonferroni/Dunn) test and Mann-Whitney test.<b>Copyright information:</b>Taken from "Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins"http://ccforum.com/content/12/1/R8Critical Care 2008;12(1):R8-R8.Published online 22 Jan 2008PMCID:PMC2374615.
Connective Tissue Research, 2018
Schulze-Tanzil (2018): Human nasoseptal chondrocytes maintain their differentiated phenotype on P... more Schulze-Tanzil (2018): Human nasoseptal chondrocytes maintain their differentiated phenotype on PLLA scaffolds produced by thermally induced phase separation and supplemented with bioactive glass 1393, Connective Tissue Research,
Cell and tissue research, 2014
Synovial fibroblasts (SF) contribute to the pathogenesis of osteoarthritis (OA), but the effects ... more Synovial fibroblasts (SF) contribute to the pathogenesis of osteoarthritis (OA), but the effects of intra-articular cytokines on SF are not completely understood. The aim of this study was to characterize the interplay between tumor necrosis factor (TNF)α and the anti-inflammatory interleukin (IL)-10. Non-immortalized human SF and SF of the human cell line K4IM were stimulated with recombinant TNFα, IL-10, or TNFα + IL-10 (10 ng/ml each) for 24 h or transduced with an adenoviral vector overexpressing human IL-10 (hIL-10) and subsequently treated with 10 ng/ml TNFα for 24 h. Effects on the gene expression and protein synthesis of IL-6, IL-10, matrix metalloproteinases (MMP)-1, -3, type I collagen, β1-integrin, and CD44 were investigated via real-time detection polymerase chain reaction, immunofluorescence labeling, flow cytometry, and Western blotting. IL-10 release by transduced SF was confirmed with enzyme-linked immunosorbent assay. Both cell populations were activated by TNFα and...
International Journal of Molecular Sciences
Successful anterior cruciate ligament (ACL) reconstructions strive for a firm bone-ligament integ... more Successful anterior cruciate ligament (ACL) reconstructions strive for a firm bone-ligament integration. With the aim to establish an enthesis-like construct, embroidered functionalized scaffolds were colonized with spheroids of osteogenically differentiated human mesenchymal stem cells (hMSCs) and lapine (l) ACL fibroblasts in this study. These triphasic poly(L-lactide-co-ε-caprolactone) and polylactic acid (P(LA-CL)/PLA) scaffolds with a bone-, a fibrocartilage transition- and a ligament zone were colonized with spheroids directly after assembly (DC) or with 14-day pre-cultured lACL fibroblast and 14-day osteogenically differentiated hMSCs spheroids (=longer pre-cultivation, LC). The scaffolds with co-cultures were cultured for 14 days. Cell vitality, DNA and sulfated glycosaminoglycan (sGAG) contents were determined. The relative gene expressions of collagen types I and X, Mohawk, Tenascin C and runt-related protein (RUNX) 2 were analyzed. Compared to the lACL spheroids, those wi...
Histochemistry and Cell Biology
Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstructi... more Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or F combined with the foam (F + coll). Cell-free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, cell vitality and content, histo(patho)logy of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed.Scaffolds did not affect mice weight development and ...
Western blot analysis of splenic Bax (left), Bcl-2 (middle), and Mcl-1 (right) expression compare... more Western blot analysis of splenic Bax (left), Bcl-2 (middle), and Mcl-1 (right) expression compared to the housekeeping gene β-actin (lower part), detected in splenocytes of sham and controls (a) as well as in HS animals (b). Results are representative of at least three animals per group and controls. *&lt; 0.05 as determined by analysis of variance (with Bonferroni/Dunn) test and Mann-Whitney test. Co, control.<b>Copyright information:</b>Taken from "Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins"http://ccforum.com/content/12/1/R8Critical Care 2008;12(1):R8-R8.Published online 22 Jan 2008PMCID:PMC2374615.
Tissue Engineering Part B: Reviews, 2010
Injured articular cartilage is limited in its capacity to heal. Autologous chondrocyte transplant... more Injured articular cartilage is limited in its capacity to heal. Autologous chondrocyte transplantation (ACT) is a suitable technique for cartilage repair, but it requires articular cartilage biopsies for sufficient autologous chondrocyte expansion in vitro. Hence, ACT is restricted by donor-site morbidity and autologous articular chondrocytes availability. The use of nonarticular heterotopic chondrocytes such as auricular, nasoseptal, or costal chondrocytes for ACT might overcome these limitations: heterotopic sources show lesser donor-site morbidity and a comparable extracellular cartilage matrix synthesis profile to articular cartilage. However, heterotopic (h)ACT poses a challenge. Particular tissue characteristics of heterotopic cartilage, divergent culturing peculiarities of heterotopic chondrocytes, and the advantages and drawbacks related to these diverse cartilage sources were critically discussed. Finally, available in vitro and in vivo experimental (h)ACT approaches were summarized. The quality of the cartilage engineered using heterotopic chondrocytes remains partly controversy due to the divergent methodologies and culture conditions used. While some encouraging in vivo results using (h)ACT have been demonstrated, standardized culturing protocols are strongly required. However, whether heterotopic chondrocytes implanted into joint cartilage defects maintain their particular tissue properties or can be adapted via tissue engineering strategies to fulfill regular articular cartilage functions requires further studies.
Critical Care, 2008
The innate immune response to trauma hemorrhage involves inflammatory mediators, thus promoting c... more The innate immune response to trauma hemorrhage involves inflammatory mediators, thus promoting cellular dysfunction as well as cell death in diverse tissues. These effects ultimately bear the risk of post-traumatic complications such as organ dysfunction, multiple organ failure, or adult respiratory distress syndrome. In this study, a murine model of resuscitated hemorrhagic shock (HS) was used to determine the apoptosis in spleen as a marker of cellular injury and reduced immune functions. Methods Male C57BL-6 mice were subjected to sham operation or resuscitated HS. At t = 0 hours, t = 24 hours, and t = 72 hours, mice were euthanized and the spleens were removed and evaluated for apoptotic changes via DNA fragmentation, caspase activities, and activation of both extrinsic and intrinsic apoptotic pathways. Spleens from untreated mice were used as control samples. Results HS was associated with distinct lymphocytopenia as early as t = 0 hours after hemorrhage without regaining baseline levels within the consecutive 72 hours when compared with sham and control groups. A rapid activation of splenic apoptosis in HS mice was observed at t = 0 hours and t = 72 hours after hemorrhage and predominantly confirmed by increased DNA fragmentation, elevated caspase-3/7, caspase-8, and caspase-9 activities, and enhanced expression of intrinsic mitochondrial proteins. Accordingly, mitochondrial pro-apoptotic Bax and antiapoptotic Bcl-2 proteins were inversely expressed within the 72hour observation period, thereby supporting significant proapoptotic changes. Solely at t = 24 hours, expression of the antiapoptotic Mcl-1 protein shows a significant increase when compared with sham-operated and control animals. Furthermore, expression of extrinsic death receptors were only slightly increased. Our data suggest that HS induces apoptotic changes in spleen through a biphasic caspase-dependent mechanism and imply a detrimental imbalance of pro-and antiapoptotic mitochondrial proteins Bax, Bcl-2, and Mcl-1, thereby promoting post-traumatic immunosuppression.
Cells, 2012
Tendon healing is generally a time-consuming process and often leads to a functionally altered re... more Tendon healing is generally a time-consuming process and often leads to a functionally altered reparative tissue. Using degradable scaffolds for tendon reconstruction still remains a compromise in view of the required high mechanical strength of tendons. Regenerative approaches based on natural decellularized allo-or xenogenic tendon extracellular matrix (ECM) have recently started to attract interest. This ECM combines the advantages of its intrinsic mechanical competence with that of providing tenogenic stimuli for immigrating cells mediated, for example, by the growth factors and other mediators entrapped within the natural ECM. A major restriction for their therapeutic application is the mainly cell-associated immunogenicity of xenogenic or allogenic tissues and, in the case of allogenic tissues, also the risk of disease transmission. A survey of approaches for tendon reconstruction using cell-free tendon ECM is presented here, whereby the problems associated with the decellularization procedures, the success of various recellularization strategies, and the applicable cell types will be thoroughly discussed. Encouraging in vivo results using cell-free ECM, as, for instance, in rabbit models, have already been reported. However, in comparison to native tendon, cells remain mostly inhomogeneously distributed in the reseeded ECM and do not align. Hence, future work should focus on the optimization of tendon ECM decellularization and recolonization strategies to restore tendon functionality.
Cells, 2012
Tendon healing is generally a time-consuming process and often leads to a functionally altered re... more Tendon healing is generally a time-consuming process and often leads to a functionally altered reparative tissue. Using degradable scaffolds for tendon reconstruction still remains a compromise in view of the required high mechanical strength of tendons. Regenerative approaches based on natural decellularized allo-or xenogenic tendon extracellular matrix (ECM) have recently started to attract interest. This ECM combines the advantages of its intrinsic mechanical competence with that of providing tenogenic stimuli for immigrating cells mediated, for example, by the growth factors and other mediators entrapped within the natural ECM. A major restriction for their therapeutic application is the mainly cell-associated immunogenicity of xenogenic or allogenic tissues and, in the case of allogenic tissues, also the risk of disease transmission. A survey of approaches for tendon reconstruction using cell-free tendon ECM is presented here, whereby the problems associated with the decellularization procedures, the success of various recellularization strategies, and the applicable cell types will be thoroughly discussed. Encouraging in vivo results using cell-free ECM, as, for instance, in rabbit models, have already been reported. However, in comparison to native tendon, cells remain mostly inhomogeneously distributed in the reseeded ECM and do not align. Hence, future work should focus on the optimization of tendon ECM decellularization and recolonization strategies to restore tendon functionality.
Muscles Ligaments and Tendons Journal, Feb 15, 2012
Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formati... more Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formation. Hence, the effect of autologous leukocytes (PBMCs, peripheral blood mononuclear cells and neutrophils) on primary rabbit Achilles tenocytes gene expression was tested in insert assisted co-cultures. Subsequently, tenocytes gene expression of extra-cellular matrix (ECM) components (type I collagen, decorin, fibronectin), the cell-ECM receptor β1-integrin, the angiogenic factor myodulin, ECM degrading matrix-metalloproteinase (MMP)1 and pro-inflammatory cytokines (interleukin [IL]-1β, tumour necrosis factor [TNFα] and IL-6) was analysed. The only significant effect of leukocytes on tenocytes ECM genes expression was a suppression of type I collagen by neutrophils combined with TNFα stimulation. The same effect could be observed analysing the β1-integrin and myodulin gene expression. However, PBMCs up-regulated significantly cytokine and MMP1 gene expression in tenocytes. These in vitro...
Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formati... more Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formation. Hence, the effect of autologous leukocytes (PBMCs, peripheral blood mononuclear cells and neutrophils) on primary rabbit Achilles tenocytes gene expression was tested in insert assisted co-cultures. Subsequently, tenocytes gene expression of extra-cellular matrix (ECM) components (type I collagen, decorin, fibronectin), the cell-ECM receptor β1-inte-grin, the angiogenic factor myodulin, ECM degrading matrix-metalloproteinase (MMP)1 and pro-in-flammatory cytokines (interleukin [IL]-1β, tumour necrosis factor [TNFα] and IL-6) was analysed. The only significant effect of leukocytes on teno-cytes ECM genes expression was a suppression of type I collagen by neutrophils combined with TNFα stimulation. The same effect could be observed analysing the β1-integrin and myodulin gene expression. However, PBMCs up-regulated significantly cytokine and MMP1 gene expression in tenocytes. These in vi...
Annals of Anatomy - Anatomischer Anzeiger
PURPOSE To provide a systematic literature review on effectiveness of arteriovenous fistula (AVF)... more PURPOSE To provide a systematic literature review on effectiveness of arteriovenous fistula (AVF) and Shunt (AVS), research animal models. BACKGROUND Due to advancing human population age, there is increased incidence of patients suffering from vascular and renal diseases leading to dialysis access using AVF and/or AVS. During those interventions native venous or synthetic grafts are arterialized. Despite temporary good patency, complications are a consequence of neointimal hyperplasia (NIH) development that contributes to patients' morbidity and mortality. Basic research attempts to elucidate the pathomechanisms so the in vivo small and large animal models are attractive. METHODS Medline search (within 1966-2018) on AVF/AVS animal models. Studies fulfilled following criteria: (1) reported complete material-methods-results section, (2) included statistically significant number of animals, (3) provided statistically significant results. 55 articles were identified encompassing six animal species used. RESULTS Large animal models include creation of AVF and AVS in pig, sheep and dog. Porcine animal models use pelvic or femoral vessels, ovine use the common carotid artery (CCA) and jugular vein (JV). Canine animal models use the femoral vessels. Small animal models use rabbit (CCA/JV), rat (JV/CCA, abdominal aorta /Vena cava inferior and femoral artery/femoral vein) and mouse (aortocaval and supraortic AVF models). CONCLUSIONS Large animal models are best for haemodynamic shear stress studies and in vivo evaluation of new synthetic vascular grafts. Small animal models, especially the genetically manipulated ones, are ideal for analysis of molecular and cellular pathomechanisms. The selection of animal species to be used depends on the addressed research question.
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Papers by Gundula Schulze-tanzil