Muscular diseases


Christian Pinset: Research Director (CECS)

Jérôme Polentes: Engineer (CECS)

Emmanuelle Massourides: Associate engineer (CECS)


Aims and background:

The objectives of the muscular disease team are to explore and validate the potential of human and dog pluripotent stem cells – human Embryonic Stem (hES) cells and induced Pluripotent Stem (iPS) cells – and their differentiated progenies to design new therapeutic strategies for muscles diseases.

Myopathies are frequent diseases and can be caused by inherited genetic defects (e.g., muscular dystrophies), or by endocrine inflammatory (e.g., polymyositis), and metabolic disorder. The common feature of myopathies is muscle atrophy. This is also observed in many chronic diseases in terminal stage including, cancer, chronic heart failure, renal failure and viral chronic infection (e.g.AIDS). Supportive and symptomatic treatments are currently the only therapeutic option to delay muscle atrophy is of critical importance in the clinics. Find new therapeutic approach to halt or to cure muscle atrophy are our main objectives regardless of etiology. For these purpose, we explore and validate the use of cell progenies derived from pluripotent stem cells to produce disease models in a dish, to screen for compounds (small molecules, biologicals, etc).

Adult human muscle precursors cells

Strategy, means and methods:

Development of biological resources from normal and pathological tissues is a required step to pursue our objectives. Pluripotent Embryonic Stem Cells and reprogrammed adult somatic cells (iPS cells) represent key cell resources to understand complex diseases and to use for their therapeutic potentials. The main advantage of the iPS cell strategy is the possibility to obtain multipotent stem cells without limitations of individuals or species). Among large animals, the dog is an extraordinary species with an extremely high quantity of human-like pathologies, correlated with the large variety of races. More 360 genetic pathologies were indeed described, from which more than 50% correspond to ortholog pathologies observed in man. We handle cells derived from two species (human and dog) and from healthy donors and individuals affected by neuromuscular diseases.

Commitment toward differentiation of pluripotent stem cells is a multi-step process that requires combination of signals. The choice of automation of cell culture and phenotypic analysis leads to define and improve differentiation protocols towards mesoderm lineages.

Phenotypic stability and unlimited self-renewal capacity of cell derived from pluripotent stem cells are essential properties for cell assay development for High Throughput Screening (HTS) strategies. HTS assays to screen for muscle-atrophy-preventing molecule are under development

Histological examination of teratoma obtained after injection of iPS in nude rat. From left to right: ectoderm; endoderm; mesoderm.

Results and future prospects:

Our recent work establishes that cells isolated from adult muscle tissue are an efficient cell material for reprogrammation. In quantitative and qualitative terms, reprogammed cells share cardinal properties of human pluripotent stems cells. Importantly, injected to nude rat, cells form teratoma with derivatives of the three germ layers. In the next step, we will use cells from patients affected by neuromuscular diseases. For these purposes, we are establishing a partnership with Jamel Chelly (Cochin, Paris, France) to produce iPS cells from muscle progenitor cells of healthy subjects and patients affected by Duchenne Muscular Dystrophy. The iPS cell strategy will extend properties of initial human muscle cells bank: a bank of unlimited growth-capacity pluripotent cells and differentiated progenies. These muscle progenies will be very useful to design gene repair strategies for DMD patients.

Dogs will be a crucial non clinical model to evaluate safety and efficacy of new therapeutics. For this reason, it will be important to be able to design iPS cells from dogs. We will adapt our strategies of gene transfer using viruses more qualifed to transduce dog cells. The use of small molecules to improve the efficacy of reprogrammation will be tested.

A first step in muscle differentiation is achieved. Indeed, we have obtained a homogenous mesodermal cell populations derived from human pluripotent stem cells (hES and iPS cells), which could represent discreet differentiation steps. Automated and combinatorial approaches are being developed to commit pluripotent stem cells toward muscle lineages.

Cell assay for HTS with cell progenies derived from pluripotent stem cells is validated to screen molecules for muscle toxicity and for the prevention of muscle atrophy. We will extend our HTS tests using different cell assays and extended chemical components libraries.



WO 2008/031957 (2008-03-20)

Christian, PINSET; (FR).

Methods for extracting and selecting cells.



  • Dr. Catherine Andre, Institut de Génétique et Développement de Rennes, CNRS UMR 6061, Université de Rennes 1, Rennes, France, (Dog genomics)
  • Dr. Jamel Chelly, Institut Cochin, Université Paris-Descartes, CNRS (UMR 8104), Paris, France, (Human muscle diseases and cell banking)