Our history

I-Stem grows along defined strategic plans

After an initial plan drafted in 2004 which laid the framework of a two-year phase (2005-2006) during which we conducted feasibility tests prior to the construction of the Institute, the second phase was prepared by a strategical plan elaborated in late 2006. It lasted three years (2007-2009) and was marked by growth of the structure and successful demonstration of the pilot programs. Phase III, which responds to a strategic plan elaborated in late 2009, runs from 2010 to 2013. It aims at fulfilling clinical expectations, enlargement of pathological indications and industrialization processes.

 

I-Stem Phase I, 2005-2006: the introductory period, team training and open lab

The first team, consisting of twenty researchers, corresponded to the first phase, “launch”, which lasted two years. It was funded by four partners including 3 associated institutions (Inserm, UEVE, AFM) and a fourth (Génopole) that gave its support to the operation. For two years – in fact rather 18 months – we have compiled a “commando team” to address three essential questions and define the principles on which to base the Institute building. The three questions were respectively on our ability to access lines of stem cells (embryonic) necessary to our research, the applicability of automated technologies to these cells, and finally the acquisition and development of scientific and technical expertise. The main principles were to define the structure of the Institute, its financing and the terms of its public and private partnerships. The construction phase of I-Stem has resulted in a work performed by a sociology lecturer and researcher in Evry, Dr Philippe Brunet, published under the title: “The trial of technoscientific work in biotechnology: the case of the Stem Cell Institute. ”

This validation focused on the following aspects:

  • build research teams of internationally recognized scientific level
  • develop research programs respectful of French law,
  • convince key financial partners of the interest and the relevance of the investment in the exploitation of the therapeutic potential of stem cells.

 

 I-Stem-Phase II, 2007-2009: growth and success of pilot demonstration

During 2006, positive assessments of Inserm and AFM led to the creation of two administrative entities that are still running, Inserm Unit 861 (joint with the University of Evry, UEVE) and the Centre for the Study of Stem Cells (CECS). Both structures were positively reassessed at the end of Phase II, a timetable consistent with the development of the third strategic plan of the Institute.

Phase II was marked by strong growth in both biological resources in equipment, number of teams and programs.

Biological resources

  • In addition to imported embryonic stem cell lines, a campaign was carried out in collaboration with the team of Professor Stéphane Viville in Strasbourg, which has enabled us to bank 19 lines from embryos discarded during a preimplantation diagnosis because of the presence of a genetic defect responsible for a severe disease.
  • In parallel, since 2008, I-Stem teams have taken the opportunity of gene reprogramming techniques developed by Shinya Yamana (published November 2007) to create many iPS cell lines carrying genetic defects.
  • Many colleagues have turned to us to have access to iPS cell lines exhibiting mutations they studied. In response, we have created the “iPS workshop “, which ensures at the same time the production of the cell lines and the formation of a member of the external team for a period of three months full-time at I-Stem. To date, more than twenty laboratories have benefited from this workshop.

Equipment

  • The start of Phase II coincided with the relocation of I-Stem in 1600 square meters, gradually extended to 2300, located within theGenopole campus I. Research space consists mainly pf confined Level II areas required for work on human cells and unconfined laboratories for biochemical experiments, molecular biology, histology and analyses.
  • The platform for high-throughput screening of compounds was installed in 2007 and implemented from mid-2008. Screening campaigns have been increasing in number every year. Itshowed itsfull power at the end of the second phase of I-Stem through allowing screening – within an industrial collaboration with Hoffman LaRoche – of 220,000 compounds.
  • The measurement tools for high content screening were installed, especially an automated imager and quantitative PCR on 384-well plates.
  • An area dedicated to animal studies, preclinical research in rodents has been implemented.

Teams

While Phase I was conducted by a small “commando”-like team without formal internal structure, phase II, marked by a doubling of the number of I-Stem members in 2007 and another doubling in 2008, led to the organization of research teams, each responsible for developing a program and under the responsibility of a team leader.

  • The majority of research teams are organized around a disease or group of diseases affecting a single organ or a single cell type. Description of the objectives and activities of the R & D is offered to the reader in a specific folder.
  • Three technological research teams are organized around major methodologies and technologies Institute (production of cells in bulk, high and medium speed screening, functional genomics)
  • In parallel, both management teams have been structured: a scientific office, responsible for the coordination and facilitation of scientific and technical activities, as well as partnerships and the administrative, financial and logistics office, dedicated to all support functions.

Programs

Team building, access to biological resources and implementation platforms have diversified approaches and programs.

  • Phase II has seen, since 2007, the first patents and the first international publications on technological programs (cell production, identification of genomic abnormalities) and biological research (identification of several differentiation protocols)
  • The arrival of several teams has diversified pathological indications in the context of two major research established at the outset, cell therapy and disease modeling paving the way for drug screening.
  • Several research collaborations have been established with academic partners and industrial pharmas and biotechs.

 

I-Stem Phase III, 2010-2013: towards therapeutic application

Since 2010, the development of I-Stem is made on the basis of a stabilized staff (between 80 and 90 employees) achieved in 2009. The purpose designated by the current strategic plan is the preparation for the transition to the clinic of results obtained in pre-clinical teams I-Stem. It is, therefore, precisely a phase of “translational research.”

  • With regard to cell therapy, we use three types of protocols for efficiently producing epidermis, striatal neurons and retinal pigmented epithelium.
  • Translational research aims to establish the conditions for, without losing effectiveness, implanting these cells  -, respectively, in patients with skin ulcers associated with sickle cell disease, Huntington’s disease and retinitis pigmentosa – optimal with respect of safety.
  • With regard to drug discovery, several molecular mechanisms involved in various pathologies were revealed by our studies of cells derived from ES or iPS lines
  • The normalization of these mechanisms using chemicals is the aim of drug screening .
  • The identification of effective compounds in vitro allows, after verification in animal models appropriate to consider the establishment of a clinical trial. This is already underway for a compound whose corrective effect was observed in cells carrying a mutation responsible for myotonic dystrophy type I.