BASIC DATA OF THE RESEARCH PROJECT
- ARRS code: J7-2594
- TITLE: The amniotic membrane as a novel multimodal therapy for bacterial cystitis and bladder cancer: unravelling its antimicrobial, immunomodulatory and anticancer activity
- PROJECT LEADER: Professor Mateja Erdani Kreft
- DURATION: 1.9.2020 - 31.8.2023
- APPLICANT RESEARCH ORGANISATION: THE FACULTY OF MEDICINE
- PARTICIPATING RESEARCH ORGANISATIONS: INSTITUTE OF ONCOLOGY LJUBLJANA
- FINANCING: Slovenian Research Agency
Scientific background and problem identification
The role of amniotic membrane (AM) is primarily to provide a suitable environment for the development of the fetus. Many of AM’s properties make it suitable for clinical use, namely it a) promotes wound healing, b) prevents inflammation and scarring, c) has low immunogenicity, and some studies also show that it has d) anticancer and e) antimicrobial properties. However, AM’s antimicrobial, immunomodulatory and anticancer efficacy has not yet been investigated in the field of urology.
Bacterial cystitis is a disease, characterized by a significant increase in number of uropathogenic bacteria in the urine together with accompanying symptoms. It is one of the most common bacterial infections in humans and is also highly recurrent. Bacterial cystitis is becoming more and more problematic to treat due to the emergence of bacteria resistant to antibiotics.
Bladder cancer is the 5th most common cancer in Europe and the 9th most common cancer worldwide. Its incidence is higher in the developed countries. Despite the advances in surgical and chemotherapeutic approaches, the prognosis of disease is still poor, mainly due to the high rates of tumour recurrence. The development of new antimicrobials and anticancer agents is therefore necessary.
Aims of the project are therefore: 1) to investigate the multimodal role of AM on biomimetic in vitro models of bacterial cystitis and bladder cancer, and on an animal model that mimics the molecular, morphological and physiological characteristics of bladder cancer; 2) to determine cell-biological mechanisms of AM activity, evaluate the safety of its use and to record its immunomodulatory role on in vitro, in vivo and patient-derived models; 3) to investigate the microbiota in the bladder of the animal model and in the urine of patients with i) bacterial cystitis, ii) bladder cancer, iii) bladder cancer and bacterial cystitis, and iv) in the urine of healthy volunteers to determine the antimicrobial efficacy of AM against uropathogenic and WHO priority pathogens; 4) to determine the relationship between urinary microbiota and the likelihood of development of bacterial cystitis and / or bladder cancer, and to provide a safety assessment of the use of AM for potential clinical use.
Organization and feasibility of the project
The project is divided into four work packages (WP), the content of which is graphically depicted in Chapter 27. In order to achieve the objective of the project, the in vitro (WP1), in vivo (WP2) and ex vivo (WP3) studies will be interconnected and will feed the downstream dissemination and exploitation process (WP4). WP4 will contribute to the final evaluation of AM for clinical use and importantly, personalized medicine. The consortium provides complementary expertise, experience and equipment, without unnecessary duplication or overlap. The success of the project is also ensured by the selection of excellent researchers and state-of-the-art equipment.
Originality and potential impact of expected results
The emergence of bacterial cystitis with bacteria resistant to antibiotics and the incidence rates of bladder cancer in Europe and worldwide are increasing and our research will be immensely important, since it will 1) provide a new multimodal therapy for the treatment of bacterial cystitis and bladder cancer by employing antimicrobial, immunomodulatory and anticancer properties of AM and 2) contribute a safety assessment of the use of AM for potential clinical use. In 2017, the WHO published a list of bacteria for which new antibiotics are urgently needed. We therefore expect that the evaluation of AM's antimicrobial efficacy against high priority pathogens will contribute to important new knowledge leading to development of new antibiotics. In addition, the elucidation of the relationship between the microbiota in the urine and the likelihood of bacterial cystitis and / or bladder cancer development will be pioneering work and will provide the necessary knowledge in this field.