Funding for "Expansion of Clinical Applications for the Human Muscle Stem Cell Product PHSat"
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The Investitionsbank Berlin (IBB) is funding the collaborative project "Expansion of Clinical Applications for the Human Muscle Stem Cell Product PHSat", initiated by the start-up company MyoPax in cooperation with the Departments of Surgery and Neurosurgery at the Charité.
Muscle diseases affect more than 20 million patients in Europe with limited therapeutic options. MyoPax, a spin-off of Charité and MDC, has developed a patented method to isolate and expand patient-specific muscle stem cell populations, known as PHSats (Primary Human Satellite-cell derived muscle stem cells), while preserving their regenerative potential.
The ProFit project aims to preclinically evaluate additional clinical applications for PHSats. The validation of new indications will lay the foundation for future clinical studies and the expansion of the market potential of PHSats. In a subproject led by Experimental Surgery and PI Priv.-Doz. Dr. Karl Hillebrandt, the preclinical application of decellularized diaphragms combined with PHSats to regenerate the impaired diaphragms of mice with muscular dystrophy will be explored. Two routes of administration will be investigated: direct injection into damaged diaphragms and transplantation onto degenerated diaphragms. The ultimate goal is to preserve or improve respiratory function by augmenting the diaphragm. This approach holds promise for several conditions, such as ventilator-induced diaphragm dysfunction or diaphragm atrophy due to COPD, where impaired diaphragm function affects respiratory capacity.
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.




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