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Stem cells from anyone?

June 6, 2007
Special to World Science  

Or­di­nary cells of the body can be “re­pro­grammed” to be­come markedly si­m­i­lar to stem cells, the “mas­ter cells” that can grow in­to many dif­fer­ent or­gans and cure a range of dis­eases, sci­en­tists say.

The find­ings are stir­ring ex­cite­ment be­cause stem cells are nor­mally ob­tain­able only from em­bryos, a pro­cess that or­di­narily kills the em­bryos and is thus fraught with eth­i­cal con­tro­ver­sy.

Re­search­ers have be­gun fig­ur­ing out ways to create stem cells without kil­ling emb­ryos in the past few years. A new ap­proach reported this week both builds and im­proves on some of these strate­gies, and could al­so side­step con­cerns about tis­sue re­jec­tion that ac­com­pa­ny oth­er stem cell treat­ments, re­search­ers said. 

This is be­cause the new pro­ce­dure raises the pos­si­bil­ity of a pa­tient be­ing treated with stem cells from his or her own body, pro­vid­ing an ex­act ge­net­ic match.

Kon­rad Hochedlinger of the Mas­sa­chu­setts Gen­er­al Hos­pi­tal in Boston and col­leagues worked with a pre­vi­ously de­vel­oped tech­nique in which four genes were added to com­mon cells called fi­brob­lasts in mice. Fi­brob­lasts are plen­ti­ful in the skin. In pre­vi­ous stud­ies, the pro­ce­dure had re­sulted in “re-setting” the cells’ ge­net­ic struc­ture to make them si­m­i­lar to stem cells, but with some no­ta­ble dif­fer­ences. 

Hochedlinger’s team com­bined this ap­proach with a new pro­ce­dure that al­lowed them to choose only the gen­er­at­ed cells that met cer­tain ge­net­ic spe­cif­ica­t­ions. This led them to find cells that they called indis­tin­guish­able, based on sev­er­al tests, from em­bry­on­ic stem cells.

Ex­perts cau­tioned that it will still be a long time be­fore such tech­niques can be per­fected and used in hu­mans, but that the re­sults are prom­is­ing.

The re­search­ers went on to show that the newly gen­er­at­ed cells could dif­fer­entiate in­to a wide range of cell types, in­clud­ing blood cells and egg cells. Hochedlinger’s find­ings ap­pear in the in­au­gu­ral July is­sue of a new re­search jour­nal, Cell Stem Cell, an af­fil­i­ate pub­lica­t­ion of the jour­nal Cell.

Two re­lat­ed stud­ies ap­pear in the July 7 is­sue of the jour­nal Na­ture. One of these found that stem-like cells si­m­i­lar to those of Ho­ch­ed­lin­ger’s team could give rise to fer­ti­lized em­bryos, al­though these lat­er died. 

A sec­ond pa­per, by a team in­clud­ing Shinya Ya­manaka of Kyo­to Un­ivers­ity, Ja­pan—who pi­o­neered the tech­nique of us­ing the four genes to re­pro­gram cells—at­tempted to in­ject si­m­i­lar cells in­to early de­vel­op­ing mouse em­bryos. The mice reached adul­thood and the re­pro­grammed cells con­tri­but­ed to and func­tioned in var­i­ous or­gans, they found. A set­back was that 20 per­cent of these mice de­vel­oped can­cer, which was blamed on one of the four genes used in the re­pro­gramming pro­cess, called c-myc.

“There may be ways to over­come this prob­lem,” Ya­manaka and col­leagues wrote. The au­thors of the oth­er Na­ture pa­per, Ru­dolf Jae­nisch of the White­head In­sti­tute for Bi­o­med­i­cal Re­search in Cam­bridge, Mass. and col­leagues, wrote that the find­ings in­di­cate that or­di­nary cells po­ten­tially can be re­pro­grammed to be­come “sim­i­lar, if not iden­ti­cal” to em­bry­on­ic stem cells.

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Homepage image: dyed mouse fibroblasts, courtesy U.S. National Institutes of Health

Ordinary cells of the body can be “reprogrammed” to become markedly similar to stem cells, the “master cells” that can grow into many different organs and cure a range of diseases, scientists say. The findings are stirring excitement because stem cells are normally obtainable only from embryos, a process that ordinarily kills the embryos and is thus fraught with ethical controversies. Researchers have begun figuring out ways around that already in the past few years. The new approach both builds and improves on some of these strategies, and could also sidestep concerns about tissue rejection that accompany other stem cell treatments, researchers said. This is because the new procedure raises the possibility of a patient being treated with stem cells from his or her own body, providing an exact genetic match. Konrad Hochedlinger from the Massachusetts General Hospital and colleagues worked with a previously developed technique in which four genes were added to common cells called fibroblasts in mice. Fibroblasts are plentiful in the skin. In previous studies, the procedure had resulted in “re-setting” the cells’ genetic structure to make them similar to stem cells, but with some notable differences. Hoedlinger’s team combined this approach with a new procedure that allowed them to choose only the generated cells that met certain genetic specifications. This leed them to find cells that they called “indistinguishable” from embryonic stem cells, based on several tests. Experts cautioned that it will still be a long time before such techniques can be perfected and used in humans, but that the results are promising. The researchers went on to show that the newly generated cells could differentiate into a wide range of cell types, including blood cells and egg cells. Hoechlinger’s findings appear in the inaugural July issue of a new research journal, Cell Stem Cell, an affiliate publication of the journal Cell. Two related studies appears in the July 7 issue of the research journal Nature. One of these studies found that stem-like cells similar to those of Hoechlinger’s team could give rise to fertilized embryos, although these later died. A second paper, by a team including Shinya Yamanaka of Kyoto University, Japan—who pioneered the technique of using the the four genes to reprogram cells—attempted to inject similar cells into early developing mouse embryos. The reprogrammed cells contributed to and functioned in various mouse organs, they found. A setback was that 20 percent of these mice developed cancer, which was blamed on one of the four genes used in the reprogramming process, called c-myc. “There may be ways to overcome this problem,” Yamanaka and colleagues wrote. The authors of the other Nature paper, Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Mass. and colleagues, wrote that the findings indicate that ordinary cells potentially can be reprogrammed to become “similar, if not identical” to embryonic stem cells.