"Long before it's in the papers"
January 13, 2008

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Researchers recreate rat heart

Jan. 13, 2008
Courtesy University of Minnesota
and World Science staff

Re­search­ers re­port that they have ar­ti­fi­cially cre­at­ed a beat­ing rat heart, with help from na­ture. 

Through a pro­cess called whole or­gan de­cel­lu­lar­iz­a­tion, Uni­vers­ity of Min­ne­so­ta sci­en­tists said they grew the or­gans by tak­ing dead ani­mal hearts and re-seed­ing them with live cells. The re­sults are de­scribed in the Jan­u­ary 13 on­line is­sue of the re­search jour­nal Na­ture Med­i­cine. 

Al­though re-cre­ating hu­man hearts may be years away, the work seems to be a prom­is­ing start, said the prin­ci­pal in­ves­ti­ga­tor, Do­ris Tay­lor of the uni­vers­ity. “The idea would be to de­vel­op trans­plantable blood ves­sels or whole or­gans that are made from your own cells.”

An estimated 550,000 heart failure cases are di­ag­nosed yearly in the Un­ited States, and some 50,000 U.S. pa­tients die an­nu­ally wait­ing for a do­nor heart.

A so­lu­tion may be “de­cel­lu­lar­iz­a­tion,” us­ing na­ture’s plat­form to cre­ate a heart, Tay­lor said. De­cel­lu­lar­iz­a­tion is the pro­cess of re­mov­ing all of the cells from an or­gan—in this case a dead an­i­mal’s heart—leav­ing in­tact the so-called ex­tra­cel­lu­lar ma­trix, the frame­work be­tween cells.

Af­ter re­mov­ing all cells from rat and pig hearts by bath­ing them in de­ter­gents, re­search­ers in­jected the re­main­ing scaf­fold with a mix­ture of pro­gen­i­tor cells from new­born rat hearts. The sci­ent­ists then placed the struc­ture in a ster­ile set­ting to grow. With­in eight days, the re­search­ers said, the hearts were pump­ing, though only at two per­cent strength com­pared to adult hearts. “The cells have many of the mark­ers we as­so­ci­ate with the heart and seem to know how to be­have like heart tis­sue,” Tay­lor said. 

“We just took na­ture’s own build­ing blocks to build a new or­gan,” said Har­ald C. Ott, co-in­ves­ti­ga­tor of the stu­dy, who now works at Mas­sa­chu­setts Gen­er­al Hos­pi­tal. “When we saw the first con­trac­tions we were speech­less.” 

Re­search­ers said they’re op­ti­mis­tic the dis­cov­ery could help in­crease the do­nor or­gan pool. The supply of do­nor or­gans is lim­it­ed. And once a heart is trans­planted, pa­tients may have to take life­long im­mune-sup­press­ing drugs, of­ten trad­ing heart fail­ure for high blood pres­sure, di­a­be­tes, and kid­ney fail­ure, Tay­lor said.

Scientists hope de­cel­lu­lar­iz­a­tion could be used to make new do­nor or­gans. Be­cause a new heart could be filled with the re­cip­i­en­t’s cells, re­search­ers hy­poth­e­size it’s much less likely to be re­jected by the body, and would be nour­ished, reg­u­lat­ed, and re­gen­er­ated in a na­tur­al way. 

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Researchers report that they have artificially created a beating rat heart, with some help from nature. Through a process called whole organ decellularization, University of Minnesota scientists grew “functioning heart tissue” by taking dead rat and pig hearts and reseeding them with live cells, the researchers said in announcing the findings. The results are described in the January 13 online issue of the research journal Nature Medicine. Although applying the process to create human hearts may be years away, the work seems to be a promising start, said the principal investigator, Doris Taylor of the university. “The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells.” Nearly 5 million people live with heart failure, and about 550,000 new cases are diagnosed each year in the United States. Approximately 50,000 United States patients die annually waiting for a donor heart. A solution may be “decellularization,” using nature’s platform to create a heart, Taylor said. Decellularization is the process of removing all of the cells from an organ—in this case a dead animal’s heart—leaving intact the so-called extracellular matrix, the framework between cells. After removing all of the cells from both rat and pig hearts, researchers injected them with a mixture of progenitor cells from newborn rat hearts and placed the structure in a sterile setting to grow. The results were very promising, Taylor said. Four days after seeding the decellularized heart scaffolds with the heart cells, contractions were seen. Eight days later, the hearts were pumping, though only at two percent strength compared to adult hearts. “Take a section of this ‘new heart’ and slice it, and cells are back in there,” Taylor said. “The cells have many of the markers we associate with the heart and seem to know how to behave like heart tissue.” “We just took nature’s own building blocks to build a new organ,” said Harald C. Ott, co-investigator of the study, who now works at Massachusetts General Hospital. “When we saw the first contractions we were speechless.” Researchers said they’re optimistic the discover could help increase the donor organ pool. In general, the supply of donor organs is limited and once a heart is transplanted, individuals face life-long immunosuppression, often trading heart failure for high blood pressure, diabetes, and kidney failure, Taylor said. Researchers hope that the decellularization process could be used to make new donor organs. Because a new heart could be filled with the recipient’s cells, researchers hypothesize it’s much less likely to be rejected by the body. And once placed in the recipient, in theory the heart would be nourished, regulated, and regenerated similar to the heart that it replaced.