诱导干细胞大家都比较熟悉，毕竟去年这个方面的研究获得诺贝尔奖，今天《自然》杂志发表一篇很有意思的论文，是在动物身体内将成熟细胞诱导成干细胞，通过转基因技术，将四种可诱导干细胞的基因让体细胞表达，利用药物启动基因表达，可以获得诱导干细胞，这种方法和体外诱导相比，显然有很大优势，因为也许可以作为一种治疗手段，将来可以在患者体内诱导出可以治疗疾病的干细胞，例如可以诱导出分泌胰岛素的beta细胞，那么就可以治疗糖尿病。当然这种方法是否有可能诱导出肿瘤也必须研究确定，但毕竟是一种比较有新意的思路。这样的思路，你想到过吗？

Stemcells created in living mice

Reprogrammed cells open door toregenerating tissues in their natural environment.

• Heidi Ledford

11 September 2013

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Researchers hope that stem cellscreated in living mice will behave more like naturally occurring stem cellsthan stem cells created in vitro.

Maria Abad & LlucMosteiro/CNIO

Researchers have reprogrammedadult mouse cells to behave like embryonic stem cells, without the need for astay in a Petri dish.

The technique, published today inNature¹, allows researchers to reprogram cells inliving mice without removing those cells from their natural environment.Initial tests suggest that these cells are able to take on a wider variety ofidentities than those generated by earlier methods.

The finding has the potential toaccelerate efforts to develop regenerative therapies by avoiding the need togrow cells outside the body and then grafting them back in place, says GeorgeDaley, a stem-cell researcher at Boston Children’s Hospital in Massachusetts,who was not involved with the study.

“This work is really at theleading edge of an advancing wave of in vivo reprogramming,” he says.“We’ve been facing big challenges recreating the physiological milieu in Petridishes and then getting those cells to functionally integrate into the body.”

Those challenges have led some todevelop methods to directly convert one cell type into another — for example,converting adult pancreatic cells from a type that aids in digestion to a typethat secretes insulin² — without removing them from the body orreprogramming them back to an embryonic state. But some researchers, includingDaley, say that such reprogramming may be the only way to create cells that canfully recapitulate specialized adult cell types.

Plastic fantastic

To reprogram cells in livingmice, a team led by Manuel Serrano, a cancer researcher at the Spanish NationalCancer Research Centre in Madrid, began by genetically engineering mice toexpress four genes that are used in culture to create induced pluripotent stem(iPS) cells — adult cells reprogrammed into an embryonic-like state. The geneswere under the control of a chemical switch; to flip it, researchers fed themice doxycycline, a type of antibiotic.

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Thea Cunningham talks to scientistsabout creating stem cells in living mice.Expressing the genes at highlevels quickly killed the mice, but when the team dialled down the doxycyclinedosage, Serrano and his team found that the mice were riddled with teratomas —disorganized tumours containing multiple cell types. Such tumours areindicative of cellular reprogramming. The researchers also found iPS cells inthe blood of the transgenic mice.

Further analysis of those iPScells showed that, compared to in vitro iPS cells, their gene expressionmore closely resembled that observed in embryos at an early stage ofdevelopment called the morula. The in vivo cells were also capable offorming a type of placental cell that no other engineered stem cell has beenable to form, and embryo-like structures in the abdominal cavities of somemice. That suggests remarkable regenerative capacity, says Daley: “It’s like they’vefound a homunculus within every cell.”

Serrano says that he and his teamare looking for an intermediate stage in which the cells could be coaxed totake on new identities without producing tumours.

Researchers also need to showthat the reprogrammed cells are capable of regenerating specific cell types ina controlled way. Serrano’s team is working to find out which cells may be mostamenable to the technique, and he has hopes of regenerating heart andinsulin-producing pancreatic cells using the method. “We have demonstratedreprogramming,” says Serrano. “Now we have to show regeneration.”

doi:10.1038/nature.2013.13725