Micro-organisms on a bio-chip

Éric Leclerc, CNRS Research Direc­tor at the joint UTC Bio­Me­chan­ics and Bio­Engi­neer­ing Lab­o­ra­to­ry (BMBI) and CNRS between 2003 and 2015, is col­lab­o­rat­ing, with­in the LIMMS (Lab­o­ra­to­ry of Inte­grat­ed Micro Mecha­tron­ic Sys­tems), in the frame­work of a joint inter­na­tion­al unit (CNRS/University of Tokyo), with Fran­co-Japan­ese teams. 

After pre­sent­ing his the­sis at the CEA in Greno­bles on “steam explo­sions, a pos­si­ble acci­den­tal occurence in nuclear pow­er plants”, Éric Leclerc, who has sol­id skills in flu­id mechan­ics, could have found him­self “in Nor­way with Total work­ing on oil extrac­tion process­es or at EDF mod­el­ling the hydraulic cir­cuits of nuclear pow­er plant cores”, but it was Japan and research that won the day. “The rea­son? I was much more inter­est­ed in the pro­pos­al from CNRS and the Uni­ver­si­ty of Tokyo to work on a new gen­er­a­tion of micro biore­ac­tors for bio­log­i­cal appli­ca­tions. In par­tic­u­lar, the cre­ation of microor­gan­isms on biochips to study the mech­a­nisms of nor­mal or patho­log­i­cal liv­er func­tion under con­di­tions close to phys­i­o­log­i­cal real­i­ty,” he points out. 

Thus, dur­ing his post-doc­tor­ate at LIMMS and in the lab­o­ra­to­ry of Pro­fes­sor Fujii (Applied Microflu­idic Sys­tems Lab) at the Insti­tute of Indus­tri­al Sci­ences of the Uni­ver­si­ty of Tokyo, Éric Leclerc began to devel­op, in part­ner­ship with Pro­fes­sor Sakai (Organs and biosys­tems engi­neer­ing Lab), organ-on-chip mod­els. This research work last­ed three years. “The aim was to cre­ate micro-envi­ron­ments, micro-biore­ac­tors to cul­ti­vate, in this case, liv­er cells while repro­duc­ing human phys­i­ol­o­gy. This allows us to test the effects of new drugs or giv­en pol­lu­tants, for exam­ple, and to be able to extrap­o­late the mod­el to humans as quick­ly and accu­rate­ly as pos­si­ble,” he explains. 

In 2003, he returned to France. For ten years, he con­tin­ued his research on the liv­er with­in the joint research unit (CNRS/UTC). The choice of liv­er? “It is a cen­tral organ in the body because any com­pound — food or med­i­cine, for exam­ple — that enters the body, either oral­ly or through the skin, will pass into the blood­stream and then into the liv­er to be trans­formed and detox­i­fied. It is quite nat­u­ral­ly that it becomes one of the first tar­get organs to under­stand the effect of a giv­en mol­e­cule on the liv­er itself and sub­se­quent­ly on the organ­ism. A drug that will be degrad­ed in the liv­er before reach­ing its tar­get will there­fore be of no inter­est. The same applies to a drug that is tox­ic to the liv­er itself,” he insists. Research that he is grad­u­al­ly extend­ing to biore­ac­tors in the kid­ney and intestines, in par­tic­u­lar. The goal was to make them work togeth­er to study the phys­i­o­log­i­cal respons­es to mul­ti-organ prob­lems,” he says. 

In 2015, he’s off again to Tokyo at LIMMS and Pro­fes­sor Sakai’s lab­o­ra­to­ry. This time, the research will con­tin­ue as part of a col­lab­o­ra­tion between the lab­o­ra­to­ries of Pro­fes­sor Fujii and Pro­fes­sor Sakai, who will be joined by Pro­fes­sor Mina­mi from the Supramol­e­c­u­lar Mate­ri­als Design Lab­o­ra­to­ry. The goal? To extend organon-a-chip tech­nolo­gies to induced pluripo­tent stem cell (iPSC) tech­nolo­gies. The inter­est of these iPSCs? “They can be repro­grammed and, in a sense, con­trolled. In short, we can con­trol cell dif­fer­en­ti­a­tion and direct it towards the pro­duc­tion of spe­cif­ic organ cells. Thus, with Pro­fes­sor Fujii, we devel­oped func­tion­al microen­vi­ron­ments with oxy­gen sen­sors to ver­i­fy oxy­gena­tion in these tis­sues; with Pro­fes­sor Sakai, we worked on the pro­to­col for trans­form­ing these cells; and final­ly, with Pro­fes­sor Mina­mi, we explored oth­er sen­sors, such as glu­cose, for exam­ple, to have a con­tin­u­ous analy­sis of cell metab­o­lism,” explains Éric Leclerc. 

The idea behind this research? “The idea is to have mod­els that repro­duce human phys­i­ol­o­gy using human cells. We can cite, for exam­ple, human mod­els for study­ing liv­er regen­er­a­tion, mod­els of human patholo­gies on which we could test mol­e­cules of inter­est (drugs) with­out going through the ani­mal test­ing phase or avoid non-phys­i­o­log­i­cal mod­els,” he explains. 

Le magazine

Avril 2024 - N°62

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