221 research outputs found

    Fogeredetű őssejtek izolálása és jellemzése = Isolation and characterisation of postnatal stem cells of dental origin

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    Kutatásainkhoz a K61543 kutatási pályázatmellé elnyertük a IN67250 nemzetközi kiegészítő támogatást is, így beszámolónk ezek összefoglaló zárójelentése. Vizsgálataink célja emberi fogbélből és parodontális ligamentumból származó őssejtek izolálása és jellemzése, in vitro modell-rendszerek és eljárások kidolgozása a fogeredetű, és így potenciálisan a fogak és a parodontális szövetek részleges vagy teljes regenerációjára felhasználható őssejtek azonosítására, izolálására és fejlődési, differenciálódási képességeik meghatározására, illetve ectodermális sejtekkel való kölcsönhatásaik jellemzésére. Munkánk során emberi fogak pulpájából (dental pulp stem cell=DPSC) és a parodontális ligamentumból (periodontal ligament stem cells=PDLSC) illetve emberi nyálmirigyekből (PTHSG) preparáltunk pluripotens őssejteket tartalmazó sejtkultúrákat. Ezen kultúrákat molekuláris és sejtbiológiai módszerekkel jellemeztük, a sejteket különböző irányú differenciálódásra / transdifferenciálódásra bírtuk. Az osteogén differenciálódás mellett ki kell emelnünk mind a DPSC, mind a PDLSC sejtek képességét a neuronális differenciálódásra az általunk kidolgozott három lépésből álló protokoll mellett. Fentieken túl egy új állatkísérletes tesztrendszert dolgoztunk ki az osseointegráció, illetve a parodontális ligamentum és a fogbél regenerációjának tanulmányozására. Mindezek megalapozzák további ilyen irányú kutatásainkat, az emberi fogeredetű sejtek in vivo regenerációs alkalmazásának kidolgozására. | The originally supported K61543 research grant received additional support by IN67250, which is a supplementary international extension of the same project. Therefore, this is a joint report of the twin grants. The purpose of our study was to isolate and characterize human stem cells from dental pulp and periodontal ligament, to develop in vitro model systems and processes, for identification of stem cells, which have the potential for full or partial regeneration dental and periodontal tissues. On the course of our work we prepared cultures containing pluripotent postnatal stem cells from the dental pulp (dental pulp stem cell=DPSC), from the periodontal ligament (periodontal ligament stem cells=PDLSC), and from the salivary glands (PTHSG). We characterized these cultures and developed methods for their differentiation / transdifferentiation in vitro. Besides the osteogenic differentiation we must highlight the potency of both DPSC and PDLSC cells for neuronal differentiation when our newly developed three step protocol is used. Moreover we also developed and in vivo animal test model for studying osseointegration, periodontal and pulp regeneration. These results will give the foundation of our future work towards the application of human stem cells of dental origin in biological regeneration of damaged tissues

    Fogeredetű posztnatális őssejtek izolálása és jellemzése = Isolation and characterisation of postnatal stem cells of dental origin

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    Kutatásainkhoz a K61543 kutatási pályázatmellé elnyertük a IN67250 nemzetközi kiegészítő támogatást is, így beszámolónk ezek összefoglaló zárójelentése. Vizsgálataink célja emberi fogbélből és parodontális ligamentumból származó őssejtek izolálása és jellemzése, in vitro modell-rendszerek és eljárások kidolgozása a fogeredetű, és így potenciálisan a fogak és a parodontális szövetek részleges vagy teljes regenerációjára felhasználható őssejtek azonosítására, izolálására és fejlődési, differenciálódási képességeik meghatározására, illetve ectodermális sejtekkel való kölcsönhatásaik jellemzésére. Munkánk során emberi fogak pulpájából (dental pulp stem cell=DPSC) és a parodontális ligamentumból (periodontal ligament stem cells=PDLSC) illetve emberi nyálmirigyekből (PTHSG) preparáltunk pluripotens őssejteket tartalmazó sejtkultúrákat. Ezen kultúrákat molekuláris és sejtbiológiai módszerekkel jellemeztük, a sejteket különböző irányú differenciálódásra / transdifferenciálódásra bírtuk. Az osteogén differenciálódás mellett ki kell emelnünk mind a DPSC, mind a PDLSC sejtek képességét a neuronális differenciálódásra az általunk kidolgozott három lépésből álló protokoll mellett. Fentieken túl egy új állatkísérletes tesztrendszert dolgoztunk ki az osseointegráció, illetve a parodontális ligamentum és a fogbél regenerációjának tanulmányozására. Mindezek megalapozzák további ilyen irányú kutatásainkat, az emberi fogeredetű sejtek in vivo regenerációs alkalmazásának kidolgozására. | The originally supported K61543 research grant received additional support by IN67250, which is a supplementary international extension of the same project. Therefore, this is a joint report of the twin grants. The purpose of our study was to isolate and characterize human stem cells from dental pulp and periodontal ligament, to develop in vitro model systems and processes, for identification of stem cells, which have the potential for full or partial regeneration dental and periodontal tissues. On the course of our work we prepared cultures containing pluripotent postnatal stem cells from the dental pulp (dental pulp stem cell=DPSC), from the periodontal ligament (periodontal ligament stem cells=PDLSC), and from the salivary glands (PTHSG). We characterized these cultures and developed methods for their differentiation / transdifferentiation in vitro. Besides the osteogenic differentiation we must highlight the potency of both DPSC and PDLSC cells for neuronal differentiation when our newly developed three step protocol is used. Moreover we also developed and in vivo animal test model for studying osseointegration, periodontal and pulp regeneration. These results will give the foundation of our future work towards the application of human stem cells of dental origin in biological regeneration of damaged tissues

    Decellularized Porcine Myocardium as a Scaffold for Cardiac Tissue Engineering

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    Myocardial infarction (MI) and heart failure are leading causes of mortality globally. Recently, cardiac tissue engineering has become an attractive option for MI treatment due to the following advantages: it might provide optimal tissue performance maintained by viable transplanted cells, and might also stimulate the formation of vasculature supplying oxygen and nutrients in the patched region. However, fabrication of a thick viable cardiac patch with 3D scaffolds that are thoroughly recellularized with desired cells remains a challenge. We hypothesize that the decellularized porcine myocardium scaffold can preserve natural extracellular matrix (ECM) structure, cardiomyocyte lacunae, mechanical properties, and vasculature templates that are able to facilitate stem cell reseeding, proliferation, cardiomyocyte differentiation, and angiogenesis. In this dissertation, we have (i) assessed the potential of the decellularized porcine myocardium as a scaffold for thick cardiac patch tissue engineering; (ii) thoroughly characterized the structural and biomechanical properties of the myocardial ECM; (iii) designed and built a novel bioreactor that could provide coordinated mechanical and electrical stimulations, and (iv) evaluated the efficiency of the multi-stimulations on the development of a cardiac tissue construct. An optimized decellularization protocol has been identified to obtain the acellular myocardial scaffold that preserves subtle ECM composition and ultrastructure. We recellularized the acellular scaffold with bone marrow mononuclear cells using a rotating bioreactor and observed successful recellularization with good cell viability, proliferation, and differentiation in a 2-week culture time. Furthermore, we have successfully built a novel bioreactor that is able to provide coordinated mechanical and electrical stimulations for facilitating stem cell differentiation and tissue construct development. We found that cardiomyocyte differentiation and tissue remodeling were more effectively and efficiently promoted with the coordinated simulations, evidenced by good cell viability, proliferation, differentiation, positive tissue remodeling, and a trend of angiogenesis in a short period of time (2 - 4 days). The clinical product that we envision will benefit from the natural architecture of myocardial ECM, which has the potential to promote stem cell differentiation, cardiac regeneration, and angiogenesis. The hopes are that our novel approach will ultimately impact thousands of patients who have suffered significant damage from a prior myocardial infarction

    Can bone marrow mesenchymal stem cells regenerate the myocardium?

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    Background: Cardiovascular diseases are the serious clinical problem, especially the loss of viable myocytes.A new approach, which provides a novel method for the treatment, is a tissue engineering andregenerative medicine. One of the current cell types used as a source to improve cardiac tissue repair,are MSCs. The aim of this study was to check if the 5’azacitidine and growth factors from cardiomyocytecell line initiate the differentiation of MSCs toward cardiomyocytes. Material and methods: Bone marrow MSCs were isolated and their biological features have been characterized.Conditioned media were prepared with the use of 5’azacitidine and growth factors releasedfrom cardiomyocytes. Results: The transdifferentiating process has been confirmed by the expression of specific muscle markers.Conditioned medium from cardiomyocyte cell line, as well as, 5’azacitidine induced muscle differentiationprocess in bone marrow MSCs in comparison to the control. Conclusions: Presented in this study data support the conclusion that this concept may represent a promisingstrategy for the repair of cardiac tissue, however, further experiments are necessary

    MESENCHYMAL STEM CELLS: AN INNOVATIVE APPROACH IN PHARMACOKINETICS

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    ABSTRACTMultipotent mesenchymal stem cells (MSCs) are special kind of stem cells which originate from mesenchyme. These cells can be used as an imperativetool to study reproductive toxicity, carcinogenicity, mutagenicity, genotoxicity, and pharmacokinetics. This novel system may reveal toxicantinducedetiology, decipher detailed understanding on molecular mechanisms of toxicants induced pathways and also enumerate the safe dose ofan investigational product. Hence, this could ultimately replace, improve or overtake current predictive models in toxicology. The particular reviewdescribes the utilization of MSCs in different field of toxicological and pharmacological research.Keywords: Mesenchymal stem cells, Toxicant, Etiology, Pharmacokinetics

    Myogenic stem cells.

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    Both skeletal muscle and bone marrow tissue contain myogenic stem cells. The population residing in muscles is heterogenic. Predominant in number are "typical" satellite cells - muscle progenitors migrating from somites during embryonic life. Another population is group of multipotent muscle stem cells which, at least in part, are derived from bone marrow. These cells are tracked by gradient of growth factors releasing from muscle during injury or exercise. Recruited bone marrow-derived cells gradually change their phenotype becoming muscle stem cells and eventually can attain satellite cell position and express Pax7 protein. Mesenchymal stem cells (MSC) isolated directly from bone marrow also display myogenic potential, although methods of induction of myogenic differentiation in vitro have not been optimized yet. Concerning efforts of exploiting myogenic stem cells in cell-mediated therapies it is important to understand the cause of impaired regenerative potential of aged muscle. Up to now, most of research data suggest that majority of age related changes in skeletal muscles are reversible, thus depending on extrinsic factors. However, irreversible intrinsic features of muscle stem cells are also taken into consideration

    Recent progress in the differentiation of bone marrow derived mesenchymal stem cells (BMMSCs) to cardiomyocyte- like cells and their clinical application

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    Bone marrow mesenchymal stem cells (BMMSCs) are one of the cells found in bone marrow stromal. A large number of studies have shown that BMMSCs cannot only differentiate into hematopoietic stromal cells, but can migrate and position themselves in multiple non-hematopoietic organizations and differentiate into the corresponding tissue cells; this characteristic demonstrates their multilineage differentiation potential. In different conditions, BMMSCs can differentiate into bone, cartilage, fat, cardiomyocyte, endothelial cells and nerve cell, etc. Because BMMSCs are easy to acquire, they can proliferate in vitro, have multi-differentiation potential after implantation in vivo, and therefore have wide application prospects for the treatment of cardiovascular disease as the ideal seed cells. This review focuses on the biological characteristics of BMMSCs, the induction and differentiation of cardiomyocyte-like cells and the application in the cardiovascular field.Key words: Bone marrow mesenchymal stem cells (BMMSCs), cardiomyocyte-like cells, cardiovascular disease

    Physiological conditions influencing regenerative potential of stem cells

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    Stem cells are being used in the treatment of cardivovascular diseases. Here, we review the physiologic and pathologic conditions that impact the regenerative potential of stem cells in the treatment of cardiovascular diseases which include the influence of donor age and the presence of metabolic syndromes. We will also discuss strategies such as pretreatment of the recipient tissue or autologous or allogeneic stem cells by growth factors or drugs and by providing a synthetic scaffold and genetic modifications that impact the regenerative potential of stem cells. Finally, we will evaluate the current state of treatment of acute or chronic cardiovascular diseases with allogeneic stem cells

    A Long Road for Stem Cells to Cure Sick Hearts: Update on Recent Clinical Trials

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    The contribution of stem cells to cure damaged hearts has finally been unraveled. A large number of preclinical and clinical studies have showed beneficial outcomes after myocardial infarction. In this review, the current understanding of stem cell therapy in preclinical and clinical experiences is summarized. Stem cells from bone marrow have shown a potential to improve cardiac performance after myocardial infarction in animal and early clinical studies. Clinical trials from all over the world have provided safety assessments of stem cell therapy with marginal improvement of clinical outcomes. Thus, further investigations should be encouraged to resolve the discrepancies between studies, clinical issues, and unclear translational findings. This review provides information and commentary on key trials for stem cell-based treat-ment of cardiovascular disease
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