The Niche

Cells reprogrammed to an embryonic-like state without viruses reported by press release

Forbes has just reported a company’s announcement that it can reprogram adult human cells to an embryonic-stem-cell-like state without using viruses. All reported successes so far use viruses to introduce new genes into the cells, a technique that most believe make them unsuitable for clinical use. At a stem-cell conference in New York, PrimeGen, based in Irvine-Calif, said that it got the technique to work by attaching “carbon-based delivery vehicles” to the proteins that the genes encode and putting the proteins inside the cells. Unusually, it announced its results outside a peeri-reviewed journal without disclosing many of the details leading to its conclusions. That means that the results are likely to be met with high skepticism from the scientific community.

There are a lot of researchers trying to reprogram cells by introducing the proteins directly. Problems that they have encountered include the fact that some proteins enter and persist in cells better than others, and it’s hard to get enough proteins in for a long enough time and in the proper ratios, which are still not understood. Research in mouse cells indicate that the proteins from the viruses need to persist for a week or more in order for reprogramming to occur.

I haven’t read anything on this specifically but the Forbes article, but here are my thoughts based on my understanding of the researchers who have successfully reprogrammed human skin cells (Kyoto University’s Shinya Yamanaka, the University of Wisconsin’s James Thomson, Harvard’s George Daley, and the University of California, Los Angeles’s Kathin Plath) and mouse skin cells (Yamanaka, Plath, Harvard’s Konrad Hochedlinger, MIT’s Rudy Jaenisch).

One problem is that it’s a lot easier to get the cells to just divide really fast than to reprogram, and these can initially resemble reprogrammed cells. The PrimeGen researchers don’t describe the techniques used to conclude that the cells as reaching the embryonic-like state. It implies that the cells have not been tested to see if they can make teratomas, weird tumors that make cells characteristic of the three main types of tissue and the most rigorous test available for human cells. PrimeGen does say that perhaps cells don’t need to be fully reprogrammed to be clinically useful.

According to the Forbes article, PrimeGen says it is collaborating with James Thomson, the scientists who first created human embryonic stem cells and leader of one of the teams that first reprogrammed differentiated cells. Thomson told Forbes he knows little about the company and denies he’s a collaborator.

The researchers say that they have reprogrammed testicular, skin, and retinal cells. There’s some evidence that testicular cells (depending on the actual type) are amenable over time in culture to becoming highly flexible cells, though less flexible than embryonic stem cells. There are several kinds of skin cells. Shinya Yamanaka recently showed that epithelial cells (cells that cover or line organs, and include some skin cells) can be reprogrammed using fewer copies of the viral genes than cultured skin cells (fibroblasts) need, which would make some cell types more amenable to being reprogrammed with proteins than others. Also, Daley found that one problem in reprogramming is that viral genes are silenced too quickly, thus inserting proteins directly might pose some advantages.

PrimeGen said that it made its announcement in order to attract investors. If a company has technology this hot, one would expect a company to approach investors with non-disclosure contracts in hand, not announce it so openly. Also, they say they need partners to expand the cells, but embryonic stem cells should be able to expand indefinitely. Also, the partners aren’t going to want to expand the cells until they know what they are. Embryonic stem cells are hard to grow, so possibly, researchers who could create the cells would have trouble growing them.

The Forbes article quotes several scientists saying they cannot evaluate the work until they see results in more detail. PrimeGen says it will soon be publishing its results in a peer-reviewed journal.

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