A group of research sci­en­tists have devel­oped a microflu­idic process capa­ble of pro­duc­ing large quan­ti­ties of blood platelets in sev­er­al hours only. Their work opens up new path­ways to in vit­ro pro­duc­tion of platelets and stems from a col­lab­o­ra­tion between physi­cists and biol­o­gists (the Gul­liv­er Lab., ESPCI Paris and the Inserm Insti­tute and the start-up Pla­tOD). The results of the stud­ies were pub­lished in Nature Sci­en­tif­ic Reports and have led to reg­is­tra­tion of a joint patent claim by ESPCI, the CNRS, Inserm and Pla­tOD. Anne Le Goff, now a research sci­en­tist at the UTC-BMBI Lab relates the inves­ti­ga­tions in which she participated. 

Blood platelets are mam­mal non-nucle­at­ed cells, only a few microns in diam­e­ter, absolute­ly nec­es­sary for blood to coag­u­late (clot). The demand for trans­fu­sion of platelets is increas­ing con­stant­ly, notably because of the mul­ti­pli­ca­tion of chemother­a­py pro­to­cols and of bone mar­row trans­plants. From a phys­i­o­log­i­cal point of view, platelets are formed by frag­men­ta­tion of the cyto­plasm of larg­er cells, the bone mar­row megakary­ocytes. We have known for a num­ber of years now that the flood flow in cap­il­lary ves­sels irri­gat­ing the mar­row plays an essen­tial role in the for­ma­tion of platelets. It was this dis­cov­ery that moti­vat­ed increased research activ­i­ties in the field of microflu­idics, to study the frag­men­ta­tion of the megakary­ocytes and blood platelet pro­duc­tion. Most sys­tems to date mime the cross­ing of the bone mar­row by the megakary­ocytes. And, although the ini­tial obser­va­tions were suc­cess­ful in show­ing how the cyto­plasm frag­ments into platelets, the quan­ti­ties of the lat­ter were far too low to enable any valid bio­log­i­cal characterization. 

The sci­en­tists in our team chose a dif­fer­ent approach, which was not lim­it­ed to repro­duc­ing exact­ly the mech­a­nisms tak­ing place in the bone mar­row. In the sys­tem they inves­ti­gat­ed, the megakary­ocyte sus­pen­sion was made to flow direct­ly in a microflu­idics cham­ber with a very large num­ber of cross-strut pil­lars to which the cells adhere, while remain­ing sub­ject to the hydro­dy­nam­ic forces at play, the lat­ter enhanc­ing their elon­ga­tion and frag­men­ta­tion. What the sci­en­tist observed was a reor­ga­ni­za­tion of the megakary­ocyte cytoskele­ton, to take on the shape of ‘pearl neck­laces’ (cf. pho­to). The cyto­plasm then sub­di­vides, under the effect of the hydro­dy­nam­ic forces and releas­es platelets into the per­fu­sion stream on a sus­tained, reg­u­lar basis. “Thanks to these hun­dreds of micro-pil­lar struc­tures in our lab-on-chip, we were able — over a two-hour peri­od — to pro­duce a suf­fi­cient quan­ti­ty of platelets, viz., enough to allow their char­ac­ter­i­za­tion. We demon­strat­ed that — as we had expect­ed — the platelets were not acti­vat­ed as they left the bio-reac­tor cham­ber but remained sen­si­tize to chem­i­cal acti­va­tion which is what we need to have them ful­fil a clot­ting func­tion in the receiver’s blood-stream“, says Mathilde Reyssat, a research sci­en­tist at the Gul­liv­er Lab, ESPCI, Paris. 

This orig­i­nal set of results derives from a rich col­lab­o­ra­tive effort by physi­cists, biol­o­gists and med­ical prac­ti­tion­ers. The aca­d­e­m­ic research staff worked hand in hands with the engi­neers from the Pla­tOD start-up, cre­at­ed by Dominique Baruch, whose objec­tive is to pro­duce platelets “on demand” with­in the next few years. 

This work is a first step towards large-scale blood platelet pro­duc­tion in vit­ro and there­fore towards new forms of trans­fu­sion pro­to­col. There is still a long list of stud­ies remain­ing to be car­ried out, such as ani­mal in vivo coag­u­la­tion tests and in the long-term, some clin­i­cal tri­als are expect­ed, in just a few years’ time.