|
|
Immunomodulatory and differentiation properties of MSCs in a mouse model of the injured cornea and retina
Kössl, Jan ; Holáň, Vladimír (advisor) ; Vištejnová, Lucie (referee) ; Heissigerová, Jarmila (referee)
Stem cells, in general, represent the potential for treating many diseases and disorders that are currently difficult to treat or the therapy has many side effects. One of the stem cells widely investigated these days are mesenchymal stem cells (MSCs). MSCs have the considerable immunomodulatory and regenerative potential for treating degenerative disorders and severe damage to various parts of the eye or other organs. Likewise, their application could serve as supportive therapy in corneal transplantation and other eye inflammatory conditions. In this study of immunomodulatory properties of MSCs, we have focused mainly on their ability to differentiate into cells of different tissue types (in our case, corneal epithelium and retina), their production of immunomodulatory molecules in the inflammatory environment, their ability to migrate to the site of the injury, and their local anti-inflammatory, regenerative, and anti-apoptotic effects. In addition, we tested the therapeutic effects of MSCs in a mouse model of ocular surface injury and a model of retinal degeneration. Finally, we investigated the mechanism of this effect in in vitro models with explants of these tissues. Limbal stem cells (LSCs) are already used to treat severe corneal damage as limbal stem cell deficiency. However, this...
|
|
|
Effect of GLP-1 on liver metabolism in experiment
Fontana, Josef ; Anděl, Michal (advisor) ; Lotková, Halka (referee) ; Vištejnová, Lucie (referee)
1 Summary GLP-1 (glucagon-like peptide-1) is a peptide hormone belonging to the group of incretins that is secreted postprandially from enteroendocrine L-cells. Number of studies described its effects to lower blood glucose level and to positively affect the B-cells of the islets of Langerhans (reducing apoptosis and accelerating their differentiation). The relationship of GLP-1 to liver cells is intensively studied. Studies described that GLP-1, its analogues or inhibition of dipeptidyl peptidase-4 have a wide range of effects in the liver. For our work was crucial that effects on lipid and saccharide metabolism in the liver were described, as well as modulation of processes related to endoplasmic reticulum stress, oxidative stress and formation of inflammatory mediators. These processes play an essential role in both: pathological conditions (eg. liver diseases NAFLD/NASH) and in the process of liver regeneration. Works describing the potential effect of incretin-based therapies in the treatment of liver diseases (especially NAFLD and NASH) were available prior to the start of our work. In contrast, results of studies on the effect of GLP-1 on the process of liver regeneration and proliferation and apoptosis of hepatocytes were very limited in the literature. The aim of our work was to elucidate the...
|
|
|
Role of Fibroblasts in Regulation of Wound Healing
Zavaďáková, Anna ; Vištejnová, Lucie (advisor) ; Buchtová, Marcela (referee) ; Krulová, Magdaléna (referee)
Dermal fibroblasts participate actively in the regulation of wound healing process. They migrate and proliferate during the proliferative phase into the wound site and respond to signals from damaged tissue by secretion of a various pro-inflammatory molecules (e.g. interleukins IL6 and IL8) and extracellular matrix components (e.g. collagen type I, hyaluronan, fibronectin). The disruption of the balance and timing of synthesis and degradation of these molecules can lead to the transition of normal to abnormal non-healing process. Several stress factors act simultaneously in this type of wounds - impaired nutrition supply, inflammation, bacterial contamination, oxidative stress etc. However, the latest in vitro research of dermal fibroblasts in wound healing apply most often only one stress factor. This thesis deals with the response of dermal fibroblasts to the wound conditions. For the first time, a comprehensive study of the functional response of the cells to the two key wound stress factors is described in 2D culture and 3D self-made collagen hydrogel culture. In the first part of the thesis response of dermal fibroblasts to the wound conditions applying two stress factors - low nutrition (2% FBS) and inflammation simulated by bacterial lipopolysaccharide (LPS) - is characterized. The...
|
|
| |
|
|
Coaxial nanofibers with incorporated suplements for regulated chondrogenic differentiation
Korbelová, Gabriela ; Rampichová, Michala (advisor) ; Vištejnová, Lucie (referee)
In the field of regenerative medicine, regeneration of cartilage defects (caused either by injury or age-related degeneration) has become a widely discussed topic. Nanofibrous scaffolds provide a suitable environment for cell adhesion, proliferation, differentiation, and also for the local involvement of bioactive substances. Nanofibrous scaffolds mimic the extracellular matrix (ECM) of hyaline cartilage. These scaffolds are seeded with autologous chondrocytes. After having been isolated from the patient, the cells must be cultivated in vitro in order to obtain a sufficient amount of chondrocytes. Scaffolds with cultivated chondrocytes are later implanted back into the pacient. Chondrocytes, however, when grown on a 2D tissue culture plastic rapidly de-differentiate and thus lose the ability to synthesize ECM molecules. The aim of the work was modulation of chondrogenic differentiation medium through finding the ideal concentration of chondrogenic supplements, composed of L-ascorbate-2-phosphate (A2P) and dexamethasone (DEX), in the culture of primary chondrocytes seeded on a nanofibrous polycaprolactone (PCL) scaffold. The effect of different concentrations of the chondrogenic supplements on chondrocyte adhesion to the scaffold and their proliferation and differentiation was studied. The influence...
|
|
|
Coaxial nanofibers with incorporated supplements for regulated chondrogenic differentiation
Korbelová, Gabriela ; Rampichová, Michala (advisor) ; Vištejnová, Lucie (referee)
In the field of regenerative medicine, regeneration of cartilage defects (caused either by injury or age-related degeneration, such as osteoporosis) has become a widely discussed topic. Nanofibrous scaffolds provide a suitable environment for cell adhesion, proliferation, differentiation, and also local involvement of bioactive substances. Nanofibrous scaffolds mimic the extracellular matrix (ECM) of hyaline cartilage and thus have the potential to treat cartilage defects. The aim of the work was modulation of chondrogenic differentiation medium through finding the ideal concentration of chondrogenic supplements, composed of ascorbate-2- phosphate and dexamethasone, in the culture of primary chondrocytes of pig origin seeded on a nanofibrous polycaprolactone (PCL) scaffold. The effect of different concentrations of the chondrogenic supplements on chondrocyte adhesion to the scaffold and their proliferation and differentiation was studied. Firstly, the influence of each of the supplements alone in the medium was studied, followed by study of effects of their combinations. Then, the supplements were incorporated into the nanofibers and their effect upon their release from the nanofibers was investiaged. The supplements were studied in 21-day experiments. The chondrogenic re- differentiation was best...
|
guest ::
