The general aim of our projects involves the characterization of cellular, molecular and functional aspects of muscle homeostasis and regeneration.
Specifically, our research focuses in three areas:
(1) Modulation of dystrophic microenvironment to improve stem cell-mediated therapy. The goal of the project is to perturb the microenvironment of dystrophic muscle, rendering it more hospitable for stem cell-mediated therapy. 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.
(2) The physiopathologic interplay between muscle and nerve.
The effective connection between muscle and nerve is crucial to the capacity of both partners to survive and function adequately throughout life. A crucial system severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. One of the best examples of impaired interplay between the nerve and muscle is observed in ALS. ALS is a disorder involving degeneration of motor neurons, muscle atrophy and paralysis. Whereas the steps leading to the pathological state are well characterized, several fundamental issues are still controversial: are the motor neurons the first and only targets of ALS? What is the contribution of muscle, if any, to the pathogenesis of ALS? These questions raised from the following considerations: i) ALS is a disease of genetic origin in which the contribution of cells and tissues other than neuronal cannot been excluded; ii) skeletal muscle, always considered just a target of the disease, is a relatively unexamined tissue that potentially directly contributes to ALS. Thus, analyzing the retrograde-talk muscle-to-nerve could be extremely important to determine if and to what degree muscle plays a role in the progression of the pathology and to develop alternative therapeutic approaches.
(3) Muscle engineered in vitro model to study muscle homeostasis and differentiation
In our laboratory it has been recently developed a 3-dimensional skeletal muscle construct, called eX-vivo Muscle engineered Tissue, X-MET. X-MET was obtained from murine skeletal muscle primary culture. The isolation from skeletal muscle of heterogeneous cell populations such as satellite cells, fibroblasts and endothelial cells, is a prerequisite of X-MET formation. Since the X-MET mimics the complex morphological properties of skeletal muscle tissue, it may be considered an ideal in vitro model of skeletal muscle, simplifying the study of complex processes such as muscle homeostasis, differentiation and muscle-nerve interplay under physiologic and pathologic conditions such as, muscular dystrophy and ALS.