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April 29, 2009

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Scientists report converting cells to new type directly

Aug. 27, 2008
Courtesy Nature
and World Science staff

Re­search­ers say they have for the first time con­vert­ed liv­ing cells di­rectly from one type to an­oth­er, a feat de­scribed by oth­er sci­en­tists as huge ad­vance in the quest to gen­er­ate spe­cif­ic cell types for med­i­cal treat­ment.

Pre­vi­ously, sci­en­tists had only been able to con­vert cells in­to dif­fer­ent types by first con­verting them in­to a prim­i­tive, un­de­vel­oped state, a char­ac­ter­is­tic of so-called stem cells.

In the new stu­dy, Doug­las Mel­ton of Har­vard Uni­ver­s­ity and col­leagues re­ported that they con­vert­ed ma­ture cells in the mouse pan­cre­as to rare in­su­lin-secreting cells, which are po­ten­tially use­ful in di­a­be­tes.

The find­ings ap­pear in the early on­line edi­tion of the re­search jour­nal Na­ture Aug. 27.

Us­ing a new ge­net­ic strat­e­gy, the in­ves­ti­ga­tors wrote that they were able to avoid first con­verting the cells to the prim­i­tive state, called pluripo­tency. The team al­so found that the newly re­pro­grammed cells could could re­duce ab­nor­mally high blood sug­ar in di­a­bet­ic mice. 

The group worked on the ba­sis of ear­li­er stud­ies of key tran­scrip­tion fac­tors—mo­le­cules that gov­ern how par­tic­u­lar genes are ac­ti­vat­ed—in­volved in de­vel­op­ment of the pan­cre­as, a large gland be­hind the stom­ach.

The re­search­ers de­fined three fac­tors that re­pro­gram a one type of pan­cre­at­ic cell, called ex­o­crine cells, in­to a sec­ond type use­ful for di­a­be­tes treat­ment, called be­ta cells. In­su­lin is a hor­mone that ena­bles cells to take up and use sug­ar. In­ad­e­quate in­su­lin pro­duc­tion re­sults in di­a­be­tes.

Al­though it re­mains to be seen wheth­er the tech­nique will work in hu­mans, the study pro­vides “proof of con­cep­t,” ac­cord­ing to Mel­ton’s team. Sci­ent­ists work could also re­pre­sent a new way to side­step mor­al prob­lems with using stem cells, which under more tra­di­tional tech­niques come from emb­ryos.

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Researchers say they have for the first time converted living cells directly from one type to another, a feat described by other scientists as huge advance in the quest to generate specific cell types for medical treatment. Previously, scientists had only been able to convert cells into different types by first converting them into a primitive, undeveloped state, a characteristic of so-called stem cells. In the new study, Douglas Melton of Harvard University and colleagues reported that they converted mature cells in the mouse pancreas to rare insulin-secreting cells, which are potentially useful in diabetes. The findings appear in the early online edition of the research journal Nature Aug. 27. Using a new genetic strategy, the investigators wrote that they were able to avoid first converting the cells to the primitive state, called pluripotency. The team also found that the newly reprogrammed cells could could reduce abnormally high blood sugar in diabetic mice. The group worked on the basis of earlier studies of key transcription factors—molecules that govern how particular genes are activated—involved in development of the pancreas, a large gland behind the stomach. The researchers defined three factors that reprogram a one type of pancreatic cell, called exocrine cells, into a second type useful for diabetes treatment, called beta cells. Insulin is a hormone that enables cells to take up and use sugar. Inadequate insulin production results in diabetes. Although it remains to be seen whether the technique will work in humans, the study provides “proof of concept,” according to Melton’s team.