Partager l'article ! Discovery in the field of Stem Cells, Cell-Therapy and Regenerative Medicine: Based in France, I am ...
Based in France, I am a former entrepreneur in the medical education sector (2000-2006) and molecular cell biology researcher in the field of stem cells, cell-therapy and regenerative medicine (2002-2008). Since 2007, I work as a freelance business strategy consultant and my clients are innovative technology-based startups/small-middle sized companies, and also organizations related to R&D and innovation (Academic research institutions, technology-transfer organizations, business/technology-clusters, startup incubators ...).
I have a discovery in the stem cells field that I would like to share it and make it live in partnership with a laboratory of an academic research institute with the goal to transfer my findings in a startup company.
Hereafter a synopsis:
My PhD researches (2003-2007) mainly focused on the study of skeletal muscle differentiation of human adipose tissue-derived mesenchymal stem cells obtained from neonate or infant donors. I also worked on other differentiations of theses cells, such as adipogenic, ostegogenic and chondrogenic differentiation.
During November 2003, I had the opportunity to visit during a week the laboratory of Pr. Terence Partridge (MRC, Faculty of Medicine, Imperial College, London). The goal of my visit was to learn how to isolate viable myofibers from mouse muscle. This protocol lets to obtain viable myofibers in culture, but also a highly pure primary culture of oligo-clonal satellite cells (muscle stem cells). This technique has been established in Prof. Partridge 's lab in 1995 and reported in this article:
As a side-project (2004-2007), I collaborated with neurologist clinicians and I had easily access to human skeletal muscle biopsies from dystrophic or healthy background. I extended with some slight modifications, the isolated myofiber technique to human skeletal muscle. I developed a unique protocol to obtain and to culture stem cells from human skeletal muscle biopsies. Modifications concern both the collagenase step of the muscle biopsy (=> noticeably better yield of viable fibers in culture) and the Growth Medium.
With my protocol, we can obtain a very naïve stem cell population, and culture these cells with a long term expansion and with retention of their myogenic potential of differentiation (stemness: extensive proliferation with self-renewal and maintaining differentiation capacity).
My protocol is undisclosed, unexploited, and not published !
Current collagenase protocols used on muscle biopsies to obtain muscle cells, in academic labs or even for clinical assays for the treatment of muscle genetic diseases (such as Duchenne Muscular Dystrophy, DMD), are very aggressive. These protocols let to obtain a population of muscle determined progenitor cells, called myoblasts. Myoblasts are not stem cells. They cannot proliferate extensively in vitro, they aged and die by replicative senescence due to the shortening of telomeres, and we have to inject millions of millions of myoblasts per each cm3 of host muscle. After injection, myoblasts massively die by apoptosis or necrosis. The functional rescue is also very weak.
My protocol could revolutionize the cell-therapy of DMD and many other skeletal muscle diseases !
We have to change the paradigm!
We have to use protocols that let to purify the real stem cells of the skeletal muscle, called satellite cells. More the cells are at the top of their ontogenic pathway, the best they are as stem cells but also as a cell source for cell-therapy. Therefore, we have to use a “gentle” protocol that does not “weak-up” (activate) satellite cells of the skeletal muscle from the G0 quiescent phase to G1/M of proliferation. Indeed, as soon as satellite cells are activated, they determine themselves in the muscle fate and become progenitor cells (myoblasts) expressing skeletal muscle transcription factors and also cytoskeleton proteins (which are certainly the cause of the sensitivity to apoptosis and necrosis). Using real muscle stem cells (instead of myoblats) for cell-therapy will also avoid to inject millions of millions of cells per each cm3 of the host muscle. Indeed, the muscle stem cells will activate inside the muscle after injection, and then they will proliferate extensively and differentiate to do their job.
Millions of millions of muscle-determined progenitor cells injected per each cm3, hundred injection points !
A thousand of naïve undetermined stem cells injected in few injection points ?
We could envision in partnership with a lab of an academic research institute, to structure 3 projects:
1) Basic Science Researches: Extensive molecular & cellular characterization of the cell population obtained with the protocol to answer these questions: What are exactly these cells? What do they express? What are their stem cell potentialities (self-renewal and differentiation capacities, in vitro and vivo)?
We will need to establish a partnership with orthopaedic surgeons and/or neurologist clinicians to provide muscle biopsies from voluntary donors (healthy or from patients) or from surgery wastes.
2) Applied Scientific Research and Pre-Clinical Assays:
- Establish the proof of concept that the cells obtained with the protocol can rescue selected human diseases (in vitro and in vivo in animal models)
- Adapt the protocol to fit with all the requirements of clinical-grade cell-therapy assays. Can we use this protocol (with or without change) in cell-therapy?
3) Patent submission and then transfer of the Industrial and Intellectual Property assets in a startup company which will be in charge of:
- the management of clinical trials for selected human diseases
- the commercialization of both the cells (direct sales of stem cells to academic laboratories or to bio-pharma companies) and the cell-therapy to hospitals or cell-therapy specialized clinics.
Since 2007-2008 (when I left the lab bench) to currently, I work as business strategy consultant for innovative technology-based startup companies based in France. But if you think that the above projects can be launched in partnership in your institute/lab or bio-pharma company, I will be glad and honored to join your team and bring all my energy and support from the bench of science to the market and the bed’s patient, with the ultimate goal to build together, shoulder to shoulder, a strong value.