A. The production of cadaver-derived hepatocytes available on the market is currently at approximately the same level as stem cell cultures. However, taking into account market price conditions, the cost of producing the latter may be halved as a result of the project, while the cost of the originator version remains unchanged. This will ultimately allow the consortium members to have stable and cost-effective supply relationships in the long term. Currently Hungary lacks the necessary capacities for “trial” procedures for mesenchimal stem cells. According to the recommendation of the EMA Advanced Therapy Working Group (EMA/CAT/571134/2009), the first human use of cell therapies should be carried out in accordance with the guidelines for other medicinal products. The relevant Directive (EMEA/CHMP/SWP/28367/07) and the relevant domestic legislation designate accredited institutes with phase I conditions as the venue for conducting such clinical trials. Despite all this, many clinical trials are carried out worldwide on the so-called “clinical exeptation” principle, which can be exploited academically and scientifically, but their marketing and use as a service is questionable. Our goal is to conduct human clinical trials in a quality and environment that can be utilised and marketable in accordance with the prevailing standards, in addition to stringent international standards. The two concurrent development activities of the project can bring the participants of the consortium to the fore not only at domestic but also international level. B. I work phase 0-18 months 1. Experimental development: As a first step, the cell laboratory of SZTE adjusts liver cell isolation methods on cadaver-derived livers and then removes liver tissue from a donor that died within 20, 24 hours after stabilisation of the processes. The detailed medical history of the deceased is also recorded, as in addition to taking medication, it can also play a major role in the metabolism processes of the deceased’s liver. 2. Industrial Research: At the same time, HR PHARMA also starts adjusting the liver cell isolation procedure by using the liver of normal Wistar (radio Wild strain) rats for this flow. 3. Industrial Research: During this time SOLVO Zrt sets out the selected five basic metabolism test methods on the market for liver cell cultures, and then compares the newly isolated human cadaver and normal animal-derived liver cell cultures. Work Phase II 19-30 months 4. Industrial Research: The cell laboratory of SZTE begins to isolate cells with regenerative potential from human adipose tissues, and then initiates hepatocyte differentiation on isolated cells using suitable media that can be purchased on the market, thus producing the hepatocyte culture from mesenchimal cells. 5. Industrial Research: At the same time, the HR Pharma TNBS model begins to prepare and isolate liver cells in experimental animals with induced diabetes and abnormally obese animals. The finished isolates will be further examined by SOLVO Zrt. In the course of a task. 6. Basic research: Solvo Zrt.'s research laboratory performs a comparison of the metabolism of stem cell cell lines prepared by SZTE, the cell cultures available on the market and those of the recently isolated cadaver origin. As a result of the studies, the use of fat-produced liver cases in the research of metabolic processes is validated. Working phase III 31 to 42 months 7. Industrial Research: A therapeutic product containing mesenchimal regenerative cells of mesenchimal origin is produced in the GMP accredited cell laboratory developed by SZTE, the first use of which is planned for the treatment of scar conditions due to burns and leg ulcers on the basis of diabetes. This is a condition for carrying out phase I studies in the associated clinical-pharmacological study section under pilot conditions. 8. Industrial Research: HR Pharma prepares further disease models by isolating liver cells in elderly, estrogen-treated and underactive thyroid animals. 9. Industrial Research: SOLVO Zrt. examines the characterisation and metabolism profile of liver cells of animals suffering from disease models (TNBS, Diabetes, Obese, Elderly, Oestrogen and Thyroid dysfunction) and compares it with the results of wild-type animals and human samples. IV work phase 43-48 months 10. Experimental development: Local anaesthesia is performed on the treated areas of patients who have undergone the SZTE in the framework of clinical trials. From the extracted tissues, the cell laboratory isolates the cells that have previously been implanted. 11. Industrial Research: At the same time, HR Pharma disease treats animals with animal models with previously unused stem cell products and isolates them from recovered tissue samples after a certain period of time.
