Preparing the ground for muscle regeneration: targeting the hostile microenvironment to improve stem cell-mediated therapy
| Componente | Categoria |
|---|---|
| Irene Casola | Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca |
| Paola Frati | Componenti strutturati del gruppo di ricerca |
| Laura Barberi | Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca |
| Vittorio Fineschi | Componenti strutturati del gruppo di ricerca |
| Componente | Qualifica | Struttura | Categoria |
|---|---|---|---|
| Carmine Nicoletti | Tecnico | SCIENZE ANATOMICHE, ISTOLOGICHE, MEDICO LEGALI E DELL'APPARATO LOCOMOTORE | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca |
Broad objectives and specific aims
The goal of the project is to perturb the microenvironment of dystrophic muscle, rendering it more hospitable for stem cell-mediated therapy.
Background/Rationale
Although stem cell research and related implications have led over the years to a considerable scientific and popular enthusiasm, the important development of regenerative medicine has determined interesting challenges from an ethical and scientific point of view. To date, cell-based therapies stalled by a limited impact of transplanted stem cell on the long term muscle cell replacement. Our working hypothesis is that the hostile dystrophic microenvironment might interfere with and limit the efficacy stem cell-mediated therapy. Thus, the entire path of research is characterized by risks, uncertainties, and problems that require a careful assessment of the foreseeable damages in relation to the expected benefits.
One of the potential candidates that contribute to sustain a hostile microenvironment in dystrophic muscle is Interleukin-6 (IL-6), a molecular marker of M1 macrophages and a critical player in the switch from acute to chronic inflammatory response. Previous work and preliminary results suggest that: i) increased levels of IL-6 exacerbate the pathological phenotype of adult mdx mice, reducing their life span and muscle functional performance; ii) blockade of endogenous IL-6R with neutralizing antibody confer on dystrophic muscles resistance to degeneration.
Description of the project
Based on the preliminary data, we will define whether the therapeutic IL-6 blockade, by the use of IL-6R blocking antibody will improve stem-cell mediated therapy, enhancing the capacity of transplanted stem cells to rescue the dystrophic phenotype.
Anticipated output
The design of a combination of dystrophin and tissue niche therapies might become a potential cornerstone approach for future DMD stem cell therapy.