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Recently, personalised approaches in the treatment of several chronic diseases such as cancer, osteoporosis, autoimmune and joint diseases are being translated from the research to the clinical practice. The goal of the personalised medicine is individualisation of therapy to achieve its optimal efficiency and safety. Laboratory medicine professionals play a key role in this process, since they provide the information needed to optimize the therapy. Researchers at the Chair of Clinical Biochemistry and Laboratory Medicine have been developing several fields of personalised (or precision) medicine, such as pharmacogenomics, nutrigenomics and cell ther-persoapy, in the context of various diseases, such as acute lymphoblastic leukaemia, chronic lymphocytic leukaemia, osteoporosis, degenerative joint disease and autoimmune diseases. Further translation of these approaches into clinical practice depends on the level of education of health professionals in this field. Thus, the incorporation of these topics into study programs is of the utmost importance. Personalizirani pristopi v obravnavi številnih kroničnih bolezni, kot so rak, osteoporoza, avtoimunske in sklepne bolezni, v zadnjem desetletju nezadržno prodirajo iz raziskovalne sfere v klinično prakso. Cilj teh pristopov je, da na osnovi genetskih in drugih dejavnikov individualiziramo zdravljenje v smislu doseganja optimalnih učinkovitosti in varnosti. Ključno vlogo v tem procesu imajo poleg zdravnikov in farmacevtov tudi strokovnjaki laboratorijske medicine, saj zagotavljajo informacije, na osnovi katerih oblikujemo optimalno zdravljenje za določenega bolnika. Na Katedri za klinično biokemijo in laboratorijsko medicino razvijamo različna področja personalizirane (oz. precizne) medicine, kot so farmakogenomika, nutrigenomika, in celično zdravljenje, in sicer v kontekstu različnih bolezni, kot so akutna limfoblastna levkemija, kronična limfatična levkemija, osteoporoza in degenerativne bolezni sklepov ter avtoimunske bolezni. Nadaljnja translacija omenjenih pristopov v klinično prakso je odvisna od stopnje izobraženosti zdravstvenih delavcev na tem področju. Zato je pomemben cilj Katedre in Fakultete za farmacijo uvajanje teh vsebin tudi v študijske programe.

Although chronic urticaria, which is often accom- panied by angioedema, is not a life-threatening condition, it can importantly deteriorate patients' quality of life. In order to explore the importance of different factors impacting the quality of life, questionnaires were prepared and distributed to CU pa tients at the Dermatovenerological Clinic, University Medical Centre Ljubljana and at the Golnik Clinic. We received completely filled in anonymous questionnaires from 38 participants (88%) out of 43 handed out to CU patients. As expected, the majority of them, i.e. 33 (87%), were females. The re sults of our study show a profound impact of the disease on the impairment of patients' quality of life. Angioedema was more common in those suffering from CU for more than 5 years. In this group of patients, the disease had also significantly more negative impacts on their self-perception and selfconfidence. Those affected by more severe forms of CU reported problems with sleeping and the social life. We also found a distinctive influence of stress on the onset, duration and seriousness of CU. Čeprav kronična urtikarija, ki jo pogosto spremlja angioedem, večinoma ne ogroža bolnikovega življenja, pa lahko izrazito poslabša njegovo kakovost. Da bi proučili vplive različnih dejavnikov na kakovost življenja bolnikov, smo pripravili anketne vprašalnike in jih razdelili preiskovancem s KU na Dermatovenerološki kliniki UKC Ljubljana in na Kliniki Golnik. Popolnoma izpolnjene anonimne ankete nam je vrnilo 38 bolnikov (88 %) od 43 povabljenih. Med njimi je bilo pričakovano več žensk, in sicer 33 ali 87 %. Izsledki naše raziskave kažejo, da bolezen izrazito poslabša kakovost življenja bolnikov. Angioedem je bil pogosteje prisoten pri tistih, ki so imeli KU že več kot 5 let. Oboleli iz te skupine so imeli tudi statistično značilno več težav z videzom in samozavestjo. Bolniki s hujšo obliko bolezni so pogosteje poročali o motnjah spanca in težavah v družabnih stikih. Naša raziskava je izpostavila tudi močan vpliv stresa na pojav, trajanje in izrazitost KU.

Mesenchymal stem cells (MSCs) present a rare and heterogeneous population of multipotent progeni- tors ubiquitously present in different tissues including those of adults. Due to their immunosuppressive capabilities and potential to regenerate various con- nective tissues such as bone, cartilage and skeletal muscles, they possess a massive potential for the treatment of various diseases and injuries of musculoskeletal tissues. Within the musculoskeletal system, most well recognized are those from bone tissue, skeletal muscles and joint membrane. Despite the vast progress in their identification and clinical use, changes within MSCs and/or their microenvironment that could potentially initiate musculoskele- tal diseases, such as osteoporosis, osteoarthritis and sarcopenia, are still poorly understood. Due to this fact, the potential of MSCs in diagnosing these conditions is still largely unexploited. The major barriers preventing the progress in this field are loose d efinition of MSCs, their tissue heterogeneity and lack of specific markers. here we provide an overview of current knowledge on the role of MSCs in musculoskeletal system, their use in regenerative medicine and their potential in diagnosing disorders of this important body system. Mezenhimske matične celice (MSC) so redka in heterogena populacija multipotentnih predhodnikov, prisotnih v številnih tkivih tudi pri odraslem človeku. Pomembne so zaradi svojih imunosupresivnih lastnosti in sposobnosti regeneracije tkiv, kot so kost, hrustanec in skeletne mišice. Zato predstavljajo velik potencial za zdravljenje bolezni in poškodb mišično skeletnega tkiva. Na tem področju so najbolj raziskane MSC iz kostnega tkiva, skeletnih mišic in sklepne ovojnice. Kljub napredku pri njihovem odkrivanju in klinični uporabi pa še vedno slabo poznamo spremembe v MSC in/ali njihovem mikrookolju, ki bi lahko bile vzrok mišično-skeletnim boleznim, kot so osteoporoza, osteoartroza in sarkopenija. Posledično je potencial MSC v diagnostiki teh patoloških stanj še neizkoriščen. Največje ovire pri napredku na tem področju so preohlapna definicija MSC, njihova tkivna heterogenost ter pomanjkanje specifičnih označevalcev. V prispevku podajamo pregled trenutnega poznavanja vloge MSC v mišično skeletnem sistemu, njihove uporabe v regenerativni medicini ter njihovega potenciala za diagnostiko bolezni tega pomembnega telesnega sistema.

Background: Dendritic cells (DCs) are considered as primary carriers of antigenic (Ag) information in the human body. This information is later presented to Ag-specific T lymphocytes in various ways that can be either immunostimulating or immunosuppressive. The latter depends on the activation status of DCs, in which way the DCs display extreme plasticity in terms of their function. Tolerogenic DCs, which are characterized by extensive immunosuppressive properties, can induce the generation of regulatory T lymphocytes or cause T-cell anergy. In the last two decades, considerable evidence has accumulated using animal models, which points to safety and efficacy of DC application in terms of treating immune-mediated diseases. Immun therapy using DCs is nowadays becoming a clinical reality. At present, a clinical study using autologous DCs derived from human monocytes and treated ex vivo to induce their immunosuppressive potential, with the aim to treat autoimmune type 1 diabetes, is registered within NIH (National Institutes of Health). Conclusion: The review discusses the characteristics of DCs, suitable for use in cellular therapy of autoimmune diseases, their role in such therapies and the way in which such cells can be generated in the laboratory. Therapy of autoimmune diseases using tolerogenic DCs represents an outstanding potential, however the major obstacles lay in the way of proper preparation of cellular products, where all procedures should follow the strict demands of good manufacturing practice (GMP). Izhodišča: Dendritične celice (DC) v človeškem organizmu so poglavitni prenašalci antigenske (Ag) informacije. Le-to posredujejo Ag-specifičnim limfocitom T v različnem smislu imunske aktivacije, ki je lahko imunostimulativna oz. imunosupresivna. Slednje je odvisno od njihovega aktivacijskega stanja, pri čemer izražajo DC izjemno funkcijsko plastičnost. Tolerogene DC, ki jih označujejo izrazite imunosupresivne značilnosti, lahko inducirajo nastanek regulacijskih limfocitov T ter povzročijo nastanek T celične anergije. V zadnjih dveh desetletjih se je nabralo dovolj eksperimentalnih dokazov na živalskih modelih, ki nakazujejo varnost in učinkovitost uporabe DC za zdravljenje imunsko posredovanih bolezni. Imunoterapija z DC tako postaja klinična stvarnost. Trenutno je v okviru NIH (National Institutes of Health) registrirana klinična študija za uporabo avtolognih DC, pridobljenih iz človeških monocitov, spremenjenih v pogojih ex vivo v smislu indukcije imunosupresivnih lastnosti, za zdravljenje avtoimunskega diabetesa tipa 1. Zaključki: Pregledni članek opisuje poglavitne lastnosti DC, primernih za uporabo v celičnem zdravljenju avtoimunskih bolezni, njihovo vlogo pri tovrstnem zdravljenju ter načine priprave te vrste celičnih pripravkov v laboratoriju. Zdravljenje avtoimunskihbolezni s tolerogenimi DC je izjemen potencial, pri čemer pa je poglavitna ovira ustrezna pridobitev celičnega proizvoda ob upoštevanju strogih načel dobre proizvodne prakse (GMP).

Background: Regulation of human immune system through mechanisms of immune tolerance is an exceptionally important part of the homeostasis that protects the integrity of our organism. Whenever we talk about immune responses, we primarily consider them as an efficient activation of numerous factors enabling our cellular and humoral immunity to protect us against nocive effects of various forms of pathogens. However, each of these activation processes must be adequately regulated by appropriate immunosuppressive mechanisms, thereby providing a rational extent of immune reactivity without exhausting the organism and at the same time assuring a rather quick reestablishment of normal physiological conditions, which is a basic task of immune homeostasis. Such natural and dynamic yin/yang balance, being crucialfor the wellbeing of each individual, can only be provided by well orchestrated specific interactions between activated effector immune cells, such as Th1, Th2 and Th17 CD4+ lymphocytes, CD8+ cytotoxic T lymphocytes, natural killer cells (NK) and other activating factors on one side, and the oppositely functioning immunoregulatory effectors, such as regulatory CD4+ andCD8+ T lymphocytes, tolerogenic antigen-presenting cells (APC) and other immunosuppressive factors, on the other. In the case of a colapse or an imbalance of this system, there are serious consequences that are reflected inthe occurrence of autoimmune diseases, in which case the immune system is unsuccessfully suppressing the reactivity against self-antigens or the outburst of cancer cells, due to the excessive negative regulatory immune mechanisms that are actively protecting tumors. Conclusions: In this review weare presenting novel findings regarding the mechanisms of tolerance as an important part of immune homeostasis and discussing the potential of translating this knowledge into clinical setting by developing advanced cell therapies, mostly for treating autoimmune diseases and preventing graft rejection following allogeneic tissue and organ transplantation. Izhodišča: Mehanizmi imunske tolerance so pomemben del homeostaze imunskega sistema, ki zagotavlja celovitost našega organizma. Ko govorimo o imunskem odzivu, največkrat pomislimo na učinkovito aktiviranje številnih dejavnikov, ki omogočajo, da se s pomočjo celične in protitelesne oziroma humoralne imunosti uspešno obranimo pred škodljivim delovanjem najrazličnejših telesu tujih snovi in dejavnikov. Pri tem pa večinoma ne razmišljamo o tem, da mora biti vsak aktivacijski obrambni mehanizem uravnan z nasprotno delujočim, zaviralnim procesom. S tem je namreč zagotovljen ustrezen obseg imunske reaktivnosti brez nepotrebnega in škodljivega izčrpavanja organizma ter razmeroma hitro vračanje na raven normalnega, uravnoteženega fiziološkega stanja, kar je osnovni cilj delovanja homeostaznih mehanizmov. Tako naravno, dinamično ravnovesje jin/jang , ki je ključno za zdravje vsakega posameznika,lahko zagotavlja le dobro nadzorovano in uravnoteženo delovanje efektorskih imunskih celic, in sicer tako aktiviranih limfocitov CD4+, vrste Th1, Th2 in Th17, citotoksičnih limfocitov CD8+, naravnih celic ubijalk (NK), limfocitov B in ostalih aktivacijskih dejavnikov na eni strani ter nasprotno delujočih imunosupresivnih celic, med katere uvrščamo različne vrste regulatornih CD4+ in CD8+ limfocitov T in tolerogenih antigene-predstavljajočih celic (APC) ter ostale zaviralne dejavnike, na drugistrani. V kolikor se to ravnovesje poruši in nagne na eno ali drugo stran, se lahko pojavijo bodisi avtoimunske bolezni, ki so posledica nepreprečene reaktivnost zoper lastne antigene, ali pa nebrzdan razrast rakavih celic zaradi prekomernega negativnega imunskega uravnavanja, ki lahko popolnoma izniči protitumorske efektorske mehanizme imunskega sistema. Zaključki: V našem prispevku predstavljamo najnovejša dognanja na področju preučevanja in razumevanja mehanizmov imunske tolerance, ki je pomembni del homeostaze pri človeku, ter potencialne možnosti za njihovo terapevtsko uporabo v obliki naprednega celičnega zdravljenja predvsem avtoimunskih bolezni ter pri preprečevanju zavrnitvenih odzivov po alogenskih presaditvah tkiv in organov.

Izhodišča: Čeprav je preživetje bolnikov s presajeno ledvico boljše kot pri dializnih bolnikih,pa z dolgoročnimi rezultati presaditev še vedno ne moremo biti zadovoljni, predvsem zaradi zapletov, povezanih s kroničnim zavrnitvenim odzivom in neželenimi učinki imunosupresivnega zdravljenja. Z vzpostavitvijo specifične imunske tolerance na darovalčeve tkivne antigene bi lahko preprečili oziroma izrazito omilili vse omenjene težave. Zaključki: Po uporabi krvotvornih matičnih celic iz kostnega mozga darovalca pred presaditvijo organa so s poskusi na laboratorijskih živalih ustvarili mešani himerizem, ki označuje vzpostavitev imunske tolerance prejemnika na tkivne antigene presadka. V preglednem članku bomo predstavili mehanizme, ki vodijo do vzpostavitve imunske tolerance, ter vlogo matičnih celic iz kostnega mozgav tem procesu, poleg tega pa tudi prepreke, s katerimi se srečujemo pri poskusih uvajanja rutinske uporabe matičnih celic pri ljudeh za običajno zdravljenje.

Background: Platelet gel is a source of many soluble proteins that can modulate tissue regeneration. Dermal fibroblasts play an important role in tissue remodeling and wound healing. Objective: The study was performed to investigate the influence of platelet gel and its active ingredients on the proliferation of human dermal fibroblasts in vitro. Methods: A fibroblast culture was established from a normal human skin biopsy. Platelet gel was prepared from platelet-rich plasma (PRP) following the addition of calcified thrombin solution. cell proliferation was measured by MTT assay. Results: We showed that platelet gel, PRP, and thrombin stimulate the proliferation of dermal fibroblasts, and that stimulation by PRP is dose dependent. Conclusion:Platelet gel can be used to treat chronic skin defects.