Translational medicine

How many patients can a doctor treat on a day, a year, or an entire career? The largest and most lasting impact is not through the individual, but through medical innovation.

Medical innovation is the result of translational research. Our health system can be only improved through continuous translation of the latest research results. After successful in vitro evaluation in the laboratory all innovations of our working group are further developed for clinical application. In line with this premise, the number of new therapeutics in clinical trials can be increased and the implementation of applied regenerative medicine can become a reality.

EmaCure® is the first wound therapy employing Hypoxia Preconditioned Products, autologous preparations of blood-derived wound healing factor proteins.

The EmaCure® therapy is prepared by conditioning peripheral blood cells under wound-simulating conditions (hypoxia, physiological temperature) for a defined period of time. This approach provides a significant improvement over currently available systems for preparation of autologous blood-based compositions as it makes it possible to deliver hypoxia-induced (i.e. angiogenesis-targeting) factor mixtures of higher protein concentration and potency, rather than only the factors already present within cells at the time of blood collection. 

The EmaCure® therapy can be delivered in the form of wound dressings and injectable preparations, which are entirely cell-free. Since the protein factors are derived from patient autologous blood, this therapy is patient-specific.

The EmaCure® wound therapy is being developed by a  multi-disciplinary team of researchers, including cell biologists, engineers, clinicians and plastic surgeons, as well as specialists in translational therapy regulation. The network of collaborating institutions includes the Technical University Munich, Hochschule München, Bogenhausen Hospital Munich, University Children's Hospital Düsseldorf, University of Applied Sciences Munich and Universitätsmedizin Göttingen.

A patent application on a one-step device for preparing and delivering the EmaCure therapy was first filed in February 2012 ((PCT/EP2013/051910;''Device based methods for localized delivery of cell-free carriers with stress-induced cellular factors'')

Project Personnel:

Maryna Jensch

Jessica Hughes

Rahmin Schams

Sanjar Bekaran

Alex Schneidinger

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Soft- Tissue- Augmentation (How to reduce inflammatory reaction of soft-tissue Fillers? How to prolong and increase retention rate of soft- tissue fillers? How to ensure accurancy and reliability of soft tissue augmentation)

Filler materials are used as a therapy for contour defects on the entire body. In addition, of course, the aesthetic application of fillers is the focus of recent research. Based on hyaluronic acid as a carrier material, additives are tested in the preclinical phase in order to reduce side effects.

To reduce forge in body reactions, to lower side effects and to enhance biocompatibility of both breast implants and soft tissue fillers Spider-Silk particle (AMsilk, Munich) coating has been employed. Having already shown benefits in small animal trails we are currently performing a study in MiniPigs, investigating the forge in body reaction, the applicability and a potential influence on capsule development of breast implants in comparison to standard hyaluronic-acid based fillers. 

Project Personnel:

Dr. Matthias Aitzetmüller

Dr. Philipp Neßbach

Chronic lymphedema is an impairement of the lymphatic system with accumulation of protein-rich fluid. In industrial nations breast cancer and its therapy is the main reason for secondary lymphedema. Until now the majority of the patients are treated conservative called CDT (complex decongestive therapy). One surgical approach is the microvascular lymph node transplantation which becomes more and more popular in recent years. The main disadvantage is an iatrogenic lymphedema on the donor site.

Our research project „Sentinel Life“ aims to develop innovative bioartificial lymph nodes for the treatment of chronic lymphedema. Therefore we just need 1 or 2 healthy lymph nodes, which are fragmented into small pieces and combined with PCL scaffolds. Those constructs can be immediately implanted into the affected site. The bioartificial lymph nodes regenerate and induce lymphangiogenesis for the improvement of lymph fluid drainage.

This innovative approach allows us to reduce the surgical risks (iatrogenic lymphedema) and operation time. Patients will be able to recover faster and to obtain a better quality of life. 

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Lipedema is characterized by localized adiposity of the lower extremities, which is typically unresponsive to dietary regimes or physical activity. Additionally to aesthetic deformity women suffer from pressure pain as well as easy bruising and progredient lymphedema. Although the disease is well described and a large number of adult women worldwide is affected, hardly any molecular research has been done on the topic.

The aim of this study was to investigate the pathophysiology of lipedema cells regarding their expression of adipogenic factors.

Until now we included 5 lipedema patients with stage II lipedema in our study. The control group consisted of 5 comparable healthy female patients with aesthetic liposuction performed in the same areas of the lateral thighs. Fat was collected through aspiration of tumescent liposuction and adipose derived stem cells (ADSCS) were isolated following protocol. Cell culture was carried out under hypoxia (1% O2) and normoxia. After 1, 4 and 7 days of culture, ELISAS (Adiponectin, Insulin like Growth factor 1,  Vascular endothelial growth factor C and Aromatase) were carried out using the supernatants of the cell cultures. In parallel cells were counted in a casy counter and an in vitro differentiation assay of ADSCs. 

Our results from the ongoing study show that the yield of cells from lipoaspiration was three times higher in lipedema patients. Cell proliferation was significantly inhibited in lipedema cells compared to normal fat cells.

Moreover it was demonstrated that hypoxia has a significant impact on IGF-1 levels, which are suppressed to a minimum in both groups compared to normoxic cultures. Lipedema cell supernatants showed increased VEGF C expression after 7 days under hypoxia compared to control cells. 

Our findings indicate that lipedema is a complex disease and further investigations with more donors, additional parameters and hormonal status will be performed to clarify pathogenesis of lipedema. 

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normales Fettgewebe I Lipödem-Fettgewebe

It is estimated that there are annually more than 250 million operations worldwide resulting in cutaneous injury and subsequent scarring. In addition to surgical incisions, there are almost 40 million traumatic injuries treated in emergency departments per year in the European Union alone. Whether the origin of the injury occurs in the operating room or is the result of trauma, the adult human body goes through a predictable series of wound healing phases (inflammation, proliferation and remodeling). All of those injuries lead to the loss of functionality, restrictions of movement and disfigurement and often cause significant impairments in everyday´s life. After injury, scar remodeling takes months to years, the complete restoration of the extra cellular matrix (ECM) is never achieved. Also the functionality of the skin never completely recovers after injury, the tensile strength scars is 70% of normal skin. It is assumed that the ECM plays a central role in scarless healing. The results obtained from this project should prove the central role of the ECM and should provide a new paradigm for treating wounds aiming for true, unimpaired tissue regeneration.

Video of Adult ECM

Fingertip injuries can be treated non-surgically with occlusive dressings and tend to regenerate nearly scar-free resulting in very good functional and aesthetic results. Split skin donor site wounds can be treated the same way to improve wound healing. As mesenchymal stem cells (MSC) are important modulators of the wound healing process, we hypothesized, that the wound fluid of fingertip injuries influences the proliferation and migration of MSCs compared to blood serum of the same patient.

We showed a strong, time-dependent effect of wound fluid on migration and proliferation of mesenchymal stem cells. MSCs are important modulators of the proliferation stage in wound healing and play an important role in the formation of scar tissue. The early activation of MSC migration could modulate scar tissue formation and could contribute to the good results of conservatively treated fingertip injuries.

Project Personnal:

Anna Wiesmeier