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Breakthrough may let scientists make stem cells on demand

Nov. 20, 2007
Special to World Science  

Two re­search teams say they appear to have suc­cess­fully turned or­di­nary hu­man cells in­to pow­er­ful stem cells, which could per­mit break­through med­i­cal treat­ments.

Stem cells are “mas­ter cells” ca­pa­ble of de­vel­op­ing in­to many or all of the hu­man body’s 220 types of cells. Al­ready used in a few ther­a­pies, stem cells are seen as po­ten­tial re­place­ments for dis­eased or dam­aged cells in con­di­tions such as di­a­be­tes, Parkin­son’s and spi­nal in­ju­ries.

Neu­ral tis­sue de­rived from hu­man skin cells mod­i­fied to be­have like em­bry­on­ic stem cells. The black scale ba­r at low­er right rep­re­sents 0.1 mil­lime­ters, or rough­ly the width of a hu­man hair. (Cour­te­sy Sci­ence)

The new find­ings may be rev­o­lu­tion­ary be­cause they could solve two key prob­lems, ex­perts said.

First, the best known way to ob­tain stem cells to date is from em­bryos, a pro­ce­dure fraught with eth­i­cal and le­gal pit­falls. The new find­ings of­fer a way around that. Sec­ond, trans­form­ing an adult’s cells back in­to stem cells would of­fer a way to cre­ate per­son­al­ized stem cells for each pa­tient, elim­i­nat­ing the com­plica­t­ion of hav­ing a pa­tient’s im­mune sys­tem re­ject stem cells from a for­eign source.

None­the­less, it re­mains to be seen wheth­er the newly minted stem cells are really as good as those from em­bryos, ex­perts said.

“Nat­u­rally oc­cur­ring hu­man em­bry­on­ic stem cells… re­main the gold stand­ard against which all al­ter­na­tive sources” of such cells must be test­ed, said Rich­ard Mur­phy, in­ter­im pres­ident of the Cal­i­for­nia In­sti­tute for Re­gen­er­a­tive Med­i­cine in San Fran­cis­co, who was­n’t in­volved in the new re­search.

Even as the sci­en­tists in­volved stressed that ca­ve­at, they dis­played pal­pa­ble ex­cite­ment over the find­ings.

“We are now fi­nally in a po­si­tion to make pa­tient-specific stem cells for ther­a­pies with­out fear of im­mune re­jection and to make disease-specific stem cells that will re­veal the un­der­ly­ing cause of many hu­man dis­eases,” said Shinya Ya­manaka of Kyo­to Un­ivers­ity, lead au­thor of one of the new re­ports.

His pa­per, to ap­pear in the Nov. 30 is­sue of the re­search jour­nal Cell, in­di­cat­ed that a cock­tail of four sub­stances called tran­scrip­tion fac­tors were suf­fi­cient to trans­form hu­man skin cells in­to cells. Tran­scrip­tion fac­tors are sub­stances pro­duced by genes, and whose main func­tion is in turn to in­flu­ence the ac­ti­vity of oth­er genes.

A separate team of re­search­ers with the Un­ivers­ity of Wis­con­sin-Madison re­ported achiev­ing si­m­i­lar re­sults in an­other re­port, pub­lished in the Nov. 23 is­sue of the jour­nal Sci­ence. 

Their tech­nique was only some­what dif­fer­ent from that of the Jap­a­nese team: they im­planted skin cells with four genes that suc­ceeded in “re­pro­gram­ming” them to a stem-cell like state. Two of the genes were those for a pair of the same tran­scrip­tion fac­tors Ya­manaka and col­leagues used.

Al­though it was­n’t clear why two dif­fer­ent recipes led to ap­par­ently very si­m­i­lar re­sults, the Wis­con­sin team wrote that they had been try­ing to avoid the use of one of the fac­tors Ya­manaka’s team used, called c-myc, be­cause of ev­i­dence that it had del­e­te­ri­ous ef­fects on some cells.

The re­search­ers were able to ze­ro in on the rel­e­vant genes, they wrote, be­cause these were among a set of genes shown to be par­tic­u­larly ac­tive in em­bry­on­ic stem cells.

Al­though there could turn out to be im­por­tant dif­fer­ences be­tween the newly gen­er­at­ed cells and true em­bry­on­ic stem cells, all the tests in­di­cate they are indistinguisha­ble, the re­search­ers in both stud­ies said. The ar­ti­fi­cial stem-like cells, they wrote, can be in­duced to turn in­to a va­ri­e­ty of dif­fer­ent cell types, like nat­u­ral stem cells. Although stem cells of cer­tain types are also ob­tain­able di­rect­ly from adults, it hasn’t been clear whe­ther these have the same ca­pa­bi­li­ties as the em­bry­o­nic type.

“The in­duced cells do all the things em­bry­on­ic stem cells do,” said stem cell sci­ent­ist James Thom­son, a mem­ber of the Un­ivers­ity of Wis­con­sin team. “It’s go­ing to com­pletely change the field.”

* * *

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Two research teams are reporting that they’ve turned ordinary human cells into what appear, by all tests, to be stem cells, which could permit breakthrough medical treatments. Stem cells are “master cells” capable of developing into many or all of the human body’s 220 types of cells. Already used in a few therapies, stem cells are seen as potential replacements for diseased or damaged cells in conditions such as diabetes, Parkinson’s and spinal injuries. The new findings may be revolutionary because they could solve two key problems, experts said. First, the best known way to obtain stem cells to date is from embryos, a procedure fraught with ethical and legal pitfalls. The new findings offer a way around that. Second, transforming an adult’s cells back into stem cells would offer a way to create personalized stem cells for each patient, eliminating the complication of having a patient’s immune system reject stem cells from a foreign source. Nonetheless, it remains to be seen whether the newly minted stem cells are really as good as those from embryos, experts said. “Naturally occurring human embryonic stem cells… remain the gold standard against which all alternative sources” of such cells must be tested,” said Richard Murphy, interim president of the California Institute for Regenerative Medicine, who wasn’t involved in the new research. Even though the scientists involved stressed that caveat, they displayed palpable excitement over the findings. “We are now finally in a position to make patient-specific stem cells for therapies without fear of immune rejection and to make disease-specific stem cells that will reveal the underlying cause of many human diseases,” said Shinya Yamanaka of Kyoto University, lead author of one of the new reports. His paper, to appear in the Nov. 30 issue of the research journal Cell, indicated that a cocktail of four substances called transcription factors were sufficient to transform human skin cells into cells. Transcription factors are substances produced by genes, and whose main function is in turn to influence the activity of other genes. Researchers with the University of Wisconsin-Madison reported achieving similar results in a separate report, published in the Nov. 23 issue of the research journal Science. Their technique was only somewhat different from that of the Japanese team: they implanted skin cells with four genes that succeeded in “reprogramming” them to a stem-cell like state. Two of the genes were those for a pair of the same transcription factors Yamanaka and colleagues used. Although it wasn’t clear why two different recipes led to apparently very similar results, the Wisconsin team wrote that they had been trying to avoid the use of one of the factors Yamanaka’s team used, called c-myc, because of evidence that it had deleterious effects on some cells. The researchers were able to zero in on the relevant genes, they wrote, because they were among a set of genes shown to be particularly active in embryonic stem cells. Although there could turn out to be important differences between the newly generated cells and true embryonic stem cells, all the tests indicate they are indistinguishable, the researchers in both studies said. The artificial stem-like cells, they wrote, can be induced to turn into a variety of different cell types, like natural stem cells. “The induced cells do all the things embryonic stem cells do,” said stem cell scientist James Thomson, a member of the University of Wisconsin team. “It’s going to completely change the field.”