Prof. Dr. Schenke-Layland
Learning from human development – Blueprints for tissue engineering
Regenerative approaches for diverse organ systems are emerging into the spotlight of science. Within the western world, heart disease is one of the most frequent health problems. Symptomatic treatment can prolong life substantially but so far there is still no curative therapy regimen available.
Novel concepts try now to fill this gap. When studying embryonic development of the heart muscle, the heart valves and the surrounding connective tissue we can learn how pathologies manifest and how we may be able to mimic heart development in a dish. In order to generate stem cell derived cardiomyocytes (ESC-CMs) it is indispensable to examine the signaling processes and the cellular cross talk between neighboring cells as well as the timing when theses signaling cues occur during development. Besides, not only the understanding of the cells themselves is important but also the constitution of the surface where they should grow on. One major challenge for transplantation of engineered cardiac tissue is to establish an appropriate scaffold for ESC-CMs. Therefore, an in-depth knowledge of biomaterials for progenitor cells is crucial to solve the problem as a whole. In the end successful tissue engineering of cardiac cells, heart valves and other organs might further improve the treatment of damaged tissues and organs.
Prof. Dr. Rodemann
Signaling cascades in control of DNA damage repair and consequences for cancer therapy
The traditional and most commonly cancer treatment concepts are surgery, radio- and chemotherapy that are more and more complemented by targeted therapies and cancer immunotherapy. Radiotherapy and most chemotherapeutics induce DNA damage that is particularly harmful to malignant cells due to their high proliferation rate, additionally feeding into genetic instability.
Signaling cascades that regulate DNA damage repair are manifold and tightly regulated in order to elicit the appropriate response for the given type of DNA defect. Depending on the extent of damage, pathways including mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER), non-homologous end-joining (NHEJ) or homology directed repair (HDR) are activated to maintain genomic integrity. The ability of a cell to successfully fix DNA strand breaks or base damages is decisive for its survival so that in cancer therapy, the treatment outcome is linked to the tumor’s ability to repair DNA. Novel concepts that make use of signaling cascades that regulate DNA damage repair pathways are now under intense investigation with the aim to sensitize tumors to chemotherapy and irradiation. Cancer cells often carry mutations in DNA damage repair genes, leading to a high degree of genetic instability and driving malignant transformation. Therefore, tumors might be more vulnerable to therapies targe ting DNA repair mechanisms and proteins than healthy tissues that have several alternative pathways to maintain their genome intact. Overall, by exploiting DNA repair signaling cascades for cancer therapies there is a great potential to improve current therapeutic concepts and to find new ways to reduce the worldwide cancer burden.
Prof. Dr. Jucker
Alzheimer´s disease begins many years before symptoms occur
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases worldwide. Early symptoms include impaired processing of new information, deteriorated spatial orientation and early memory problems. However, there is strong evidence that the disease begins in brain many years before obvious neuron loss occurs and clinical symptoms become apparent. One of the earliest changes are the aggregation of Aß peptide and tau protein in brain that subsequently initiate a pathogenic cascade that leads to AD dementia. Understanding the molecular and cellular mechanism underlying these early, pre-clinical stages of AD has become of great importance for prevention and therapeutic strategies.
PD Dr. Ateschrang
Reconstructive surgery in orthopedics – Challenges for clinics and research
Musculoskeletal defects, joint degeneration and injury as well as ligament or tendon avulsion are common clinical causes in young and elderly that often require surgical procedures. Also, cartilage or the ligamentous apparatus have a limited capacity to regenerate after severe injuries. Besides, it remains a major challenge for orthopedics, to preserve the complex locomotor system and its functionality after surgical procedures.
There has been made notable progress in reconstructive surgery providing chances to improve or cure diseases of the musculoskeletal system. For example, cell-based approaches are on the rise to repair degenerated cartilage by culturing and expanding patient-derived chondrocytes that can be transplanted back into the injured joint. However, so far it is not possible to treat advanced arthrosis with this technique as the defect size exceeds the possible transplant size. Moreover, not all types of cartilage can be grown for clinical use in a cell culture as it is the case for fibrocartilage, making up the meniscus or the intervertebral discs. In terms of mechanical fixation there are likewise new concepts that intend to retain the ruptured ligament rather than replace it by a healthy piece of tendon. To date, novel therapy regimens are often only feasible in a small cohort of patients that match tight requirements. Therefore, to provide the best treatment to everyone and to insure a long-term effect or a full recovery, it is important to link clinical approaches with innovative concepts from basic science. By this means it might be possible to establish more personalized cell-based methods or to implement biomaterials having the exact consistency that are required in clinics.
Prof. Dr. Stenzl
Age-related urinary incontinence and possible ways of treatment
Stress urinary incontinence (SUI) is characterized by frequent and involuntary loss of urine and manifests in particular with increasing age. Approximately every tenth men and 15 out of 100 women are affected by urinary incontinence once in their lifetime and conventional therapies are not always successful. Upon histological examination, the causal urethral sphincter weakness or dysfunction shows fibrosis and a reduced number of myocytes in the affected muscle tissue.
In case of SUI, which is the most common form of urinary incontinence, autologous progenitor cells like mesenchymal stromal cells (MSCs) bear the potential to regenerate urinary sphincter muscles, one day. MSCs can be obtained from bone marrow or from adipose tissue. In vitro, these human progenitor cells can be expanded and differentiated into striated as well as smooth muscle cells. In a pre-clinical model, the application of these differentiated cells for Regenerative Sphincter Therapy (ReST) is under investigation. Moreover, novel imaging technologies allow tracking and assessing the behavior of labeled cells after injection in situ.
Concerning the individual and complex disease situation with special attention to the etiology of urinary incontinence, muscular and neurological status of the urethra and bladder as well as the suitability for regenerative therapy and capacity of wound healing, ReST is a promising approach significantly improving the therapeutic options in urinary incontinence.
Prof. Dr. Kleger
Pluripotent stem cell derived organoids to study gastrointestinal disease
Stem cell technologies always raised hopes for a better treatment of damaged tissues or organ transplantation. But not only for regenerative approaches, also to perform disease modelling, stem cell-based models have proved to be a valuable tool.
Recently, stem cell-derived mini-organs - so called organoids - have been generated to study gastrointestinal development and disease. There are several approaches to grow organoids: One method is based on using pluripotent stem cells (PSCs) that are either reprogrammed somatic cells (iPSCs) or embryonic stem cells (ESCs). PSCs undergo directed differentiation where they pass several stages of human development until they finally resemble the organ of interest. Organoids can also be generated by using adult stem cells which are organ-specific and can give rise to the organ tissue of their origin. After establishing an organoid culture these cellular three-dimensional constructs can be applied for cancer studies when introducing cancer-driving mutations. Also, it is possible to model infections or gene therapy in those mini-organs. Finally, even broad drug screening can be done, bridging standard cell culture procedures and animal studies. Overall, human organoids have a high potential to shed light in several research areas due to their versatile field of application and might revolutionize life science and tissue engineering.
Molecular Medicine SymposiumThis is a joint event of the Student council department Molecular Medicine Tübingen “Fachschaft Molekulare Medizin Tübingen e.V.” and the Medical faculty of the University Tübingen
June 03 - 05
Fachschaft Molekulare Medizin Tübingen
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