Mesenchymal Stromal Cell Therapy for Recessive Dystrophic EB (RDEB) (Bruckner-Tuderman Handgretinger 1)Completed
|Prof Leena Bruckner-Tuderman, Rupert Handgretinger
|University of Freiburg Medical Center, Freiburg, GERMANY
|Start date / Duration
|01. Jan 2013 / 36 months
|Funder(s) / Co-Funder(s)
|DEBRA Austria, MSAP/EBEP Recommended
Short lay summary
Dystrophic epidermolysis bullosa (DEB) is caused by loss of function of collagen VII (C7), an adhesive protein which firmly attaches the outermost skin layer, the epidermis, with the underlying layer, the dermis. C7 is pivotal for the barrier function of the skin and its ability to resist mechanical stress. Currently, no cure exists for DEB, and the treatments are symptomatic.
This project deals with mesenchymal stromal cells (MSC) and their therapeutic potential to improve DEB and alleviate symptoms. MSC can be isolated from a number of sources such as bone marrow, umbilical cord blood, or adipose tissue, and they have been successfully used to treat other human diseases, which have certain biological similarities to C7 and DEB. MSC have stem cell-like properties, and the hypothesis is that they can develop into C7 producing cells when they come into contact with the dermis.
The goal of this project is to test intradermally injected MSC as a form of cell therapy to improve DEB. For this, we combine expertise in pediatric hematology / MSC-isolation and in DEB research. In the first step, MSC were isolated from nine individual healthy donors and expanded under optimized culture conditions. Laboratory analyses showed two very positive things: 1) the MSC produce as much C7 as normal skin cells; 2) variation between individual healthy donors is low. The next step was to treat a DEB-mouse with the human MSC. This mouse has very little own C7 and shows all the signs and symptoms of DEB. Again here, significant results were obtained. Localized injection of human MSC into the skin of these mice led to: 1) clearly increased C7 content in the appropriate location along the dermal-epidermal junction; 2) increased C7 content at borders of healing wounds; 3) the collagen was derived from the injected therapeutic MSC, not other skin cells which may produce mutated, less functional C7; 4) importantly, the mice showed no adverse effects of the treatment. Taken together, our studies have so far indicated that locally injected stem cell-like MSC are safe and efficient in increasing C7 content in the skin. Based on this, improved skin integrity and enhanced wound healing can be expected. Thus, MSC, if present in sufficient numbers, may represent an efficacious cell-based therapy for DEB, especially for DEB-related wounds. Further studies must determine if systemic administration of MSC can provide sufficiently high cell numbers in the skin and thus render large body surfaces amenable to treatment.