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Can Frankenstein and a baby’s heartbeat unlock the mystery of stem cells?

June 24, 2013

New biowire technology matures human heart cells by mimicking fetal heartrate

TORONTO, ON – A new method of matur­ing human heart cells that sim­u­lates the nat­ur­al growth envi­ron­ment of heart cells while apply­ing elec­tri­cal puls­es to mim­ic the heart rate of fetal humans has led researchers at the Uni­ver­si­ty of Toron­to to an elec­tri­fy­ing step for­ward for car­diac research.

The dis­cov­ery, announced this week in the sci­en­tif­ic jour­nal Nature Meth­ods, offers car­diac researchers a fast and reli­able method of cre­at­ing mature human car­diac patch­es in a range of sizes.

“You can­not obtain human car­diomy­ocytes (heart cells) from human patients,” explains Mil­i­ca Radis­ic, Cana­da Research Chair in Func­tion­al Car­dio­vas­cu­lar Tis­sue Engi­neer­ing and Asso­ciate Pro­fes­sor at the Insti­tute of Bio­ma­te­ri­als & Bio­med­ical Engi­neer­ing (IBBME) and the Depart­ment of Chem­i­cal Engi­neer­ing.

Because human heart cells – inte­gral for study­ing the effects of car­diac drugs, for instance – do not nat­u­ral­ly repro­duce in large num­bers, to date researchers have been using heart cells derived from “repro­grammed” human induced pluripo­tent stem cells, or hiPSC’s, which tend to be too imma­ture to use effec­tive­ly in research or trans­plan­ta­tion.

“The ques­tion is: if you want to test drugs or treat adult patients, do you want to use cells and look like and func­tion like fetal car­diomy­ocytes?” asks Radis­ic, who was named a “Top Inno­va­tor Under 35” by MIT Tech­nol­o­gy Review and more recent­ly was award­ed the Order of Ontario and the Young Engi­neers of Cana­da 2012 Achieve­ment Award. “Can we mature these cells to become more like adult cells?”

In response to the chal­lenge, Radis­ic and her team — which includes IBBME grad­u­ate stu­dent Jason Mik­las and Dr. Sara Nunes, a sci­en­tist at the Uni­ver­si­ty Health Net­work (UHN) in Toron­to — cre­at­ed a ‘biowire’. Human heart cells derives from stem cells are seed­ed along a silk suture typ­i­cal to med­ical appli­ca­tions. The suture allows the cells to grow along its length, close to their nat­ur­al growth pat­tern.

Like a scene lift­ed from Franken­stein, the cells are then treat­ed to cycles of elec­tric puls­es, like a mild ver­sion of a pace­mak­er, which have been show to stim­u­late the cells to increase in size, con­nect and beat like a real heart tis­sue.

But the key to suc­cess­ful­ly and rapid­ly matur­ing the cells turns out to be the way the puls­es are applied.

Mim­ic­k­ing the con­di­tions that occur in fetal car­diac devel­op­ment, when the heart rates esca­lates pri­or to birth, the team ramped up the rate at which the cells were being stim­u­lat­ed, from zero to 180 and 360 beats per minute.

“We found that push­ing the cells to their lim­its over the course of a week derived the best effect,” reports Radis­ic.

Grown on sutures that can be sewn direct­ly into a patient, the biowires are designed to be ful­ly trans­plantable. The use of biodegrad­able sutures, impor­tant in sur­gi­cal patch­es that will remain in the body, is also a viable option.

Mik­las argues that the research has prac­ti­cal impli­ca­tions for health care. “With this dis­cov­ery we can reduce costs on the health care sys­tem by cre­at­ing more accu­rate drug screen­ing.”

Accord­ing to Nunes, though, the devel­op­ment takes car­diac research just one step clos­er to viable car­diac patch­es.

“One of the great­est chal­lenges of trans­plant­i­ng these patch­es is get­ting the cells to sur­vive,” explains Nunes, who is both a car­diac and a vas­cu­lar­iza­tion spe­cial­ist, “and for that they need the blood ves­sels. Our next chal­lenge is to put the vas­cu­lar­iza­tion togeth­er with car­diac cells.”

Yet Radis­ic, who calls the new method a “game chang­er,” is quick to point out just how far the field has come in a very short time.

“In 2006 sci­ence saw the first deriva­tion of induced pluripo­tent stem cells from mice,” she explains. “Now we can turn stem cells into car­diac cells and make rel­a­tive­ly mature tis­sue from human sam­ples with­out eth­i­cal con­cerns.”


The Insti­tute of Bio­ma­te­ri­als and Bio­med­ical Engi­neer­ing (IBBME) is an inter­dis­ci­pli­nary unit sit­u­at­ed between three Fac­ul­ties at the Uni­ver­si­ty of Toron­to: Applied Sci­ence and Engi­neer­ing, Den­tistry and Med­i­cine.

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For more infor­ma­tion, con­tact:

Erin Vol­lick
Senior Com­mu­ni­ca­tions, Media and Alum­ni Rela­tions Offi­cer
Insti­tute of Bio­ma­te­ri­als and Bio­med­ical Engi­neer­ing
Cell: (416) 409‑4633