Media Releases

U of T researchers identify optimal structure and cell ratio of heart

November 20, 2013

Researchers initial discovery leads to creation of first-ever living, three-dimensional human arrhythmic tissue

TORONTO, ON — Researchers at the Uni­ver­si­ty of Toronto’s Insti­tute of Bio­ma­te­ri­als & Bio­med­ical Engi­neer­ing (IBBME) and the McEwen Cen­tre for Regen­er­a­tive Med­i­cine have iden­ti­fied the opti­mal struc­ture and cell ratio asso­ci­at­ed with heart func­tion – and the dis­cov­ery has already led the team to anoth­er research first: the engi­neer­ing of the first-ever liv­ing, three-dimen­sion­al human arrhyth­mic tis­sue. The team’s foun­da­tion­al study will be pub­lished in this week’s bio­med­ical jour­nal PNAS (Pro­ceed­ings of the Nation­al Acad­e­my of Sci­ence).

The study marks the first time that researchers have tried to define and for­mu­late the pre­cise type and ratio of cell types that pro­duce high­ly func­tion­al car­diac tis­sue.

“Hearts are not just com­posed of one type of cell,” explained fourth-year IBBME PhD Stu­dent Nimalan Tha­vandi­ran and first author of the PNAS study. But until now, sci­en­tists have not known how to mix dif­fer­ent cell types in engi­neered heart tis­sue in such a way that the tis­sue achieves the com­po­si­tion and matu­ri­ty lev­el of the native human heart.

Tha­vandi­ran solved this mys­tery by method­i­cal­ly sep­a­rat­ing dif­fer­ent cell types derived from human pluripo­tent stem cells and pre­cise­ly mix­ing them back togeth­er. Using scor­ing met­rics asso­ci­at­ed with func­tion­al hearts — con­trac­tion, elec­tri­cal activ­i­ty and cell align­ment – Tha­vandi­ran was able to devel­op a for­mu­la for engi­neer­ing high­ly func­tion­al heart tis­sue.

“The com­po­si­tion of the cells is vital,” stat­ed Tha­vandi­ran. “We dis­cov­ered that a mix­ture of 25% car­diac fibrob­lasts (skin-like cells) to 75% car­diomy­octes (heart cells) worked best.” The care­ful­ly com­posed cell ratios were then grown in three-dimen­sion­al “wires” that mim­ic the struc­ture of human heart tis­sue.

“An excit­ing result of our study is our abil­i­ty to minia­tur­ize the tis­sues into human heart micro-tis­sues that can be used to mea­sure nor­mal and dis­eased human heart respons­es to drugs,” empha­sized Pro­fes­sor Peter Zand­stra, cor­re­spond­ing author of the study and Cana­da Research Chair in Stem Cell Bio­engi­neer­ing at IBBME and the McEwen Cen­tre for Regen­er­a­tive Med­i­cine.

From dis­cov­er­ing the right com­po­si­tion of heart cells, the researchers next designed the first-ever three-dimen­sion­al arrhyth­mia tis­sue mod­el. Since human heart cells aren’t eas­i­ly grown, being able to engi­neer high­ly func­tion­al heart tis­sue from human stem cells is a vital con­cern for car­diac researchers.

Mil­lions of peo­ple expe­ri­ence arrhyth­mia each year, a con­di­tion in which the feed­back of elec­tri­cal puls­es of the heart is inter­rupt­ed, leav­ing the heart unable to con­tract and pump blood effec­tive­ly.

With the right cel­lu­lar com­po­si­tion, the researchers engi­neered the cir­cu­lar tis­sue mod­el asso­ci­at­ed with arrhyth­mia. The team then applied elec­tri­cal puls­es to the arrhyth­mic tis­sues, ‘zap­ping’ the irreg­u­lar­ly beat­ing tis­sue into a state of reg­u­lar con­trac­tions.


The Uni­ver­si­ty of Toronto’s Insti­tute of Bio­ma­te­ri­als & Bio­med­ical Engi­neer­ing (IBBME) is a unique, mul­ti­dis­ci­pli­nary grad­u­ate research unit at the at the cut­ting edge of inno­va­tion in bio­med­ical engi­neer­ing – where inves­ti­ga­tors from the fac­ul­ties of engi­neer­ing, med­i­cine and den­tistry col­lab­o­rate to find inno­v­a­tive solu­tions to the world’s most press­ing health care chal­lenges.


For more infor­ma­tion, con­tact:

Erin Vol­lick
Senior Com­mu­ni­ca­tions Offi­cer
Insti­tute of Bio­ma­te­ri­als & Bio­med­ical Engi­neer­ing (IBBME)
Uni­ver­si­ty of Toron­to
Tel: 416.946.8019