Live mice from stem cells!

cwilcox — Fri, 24 Jul 2009 11:31:00 +0000

News today has spread about new stem cell research out of China. Two teams used mouse fibroblasts, a kind of cell found in skin connective tissues, to create induced pluripotent skin cells (iPS), which were then used to create living mice.

Their breakthrough research suggests that both cloning full animals from stem cells and the creation of completely pluripotent stem cells from skin cells are both not only possible, but a current reality. The two teams published separately, in Nature and Cell - Stem Cell, both very prestigious journals.

The first task for either study was to create stem cells from non stem cells. Embryonic stem cells, controversial because they often come from the destruction of live embryos, are what is called "pluripotent," which means they can become any cell in the body. To be able to create cells that act like embryonic stem cells, without the embryo part, opens to door to a fascinating and less-controversial field of medical research, including organ repair or even full organ replacements that are guaranteed to match the host's body. Just imagine never having to look for donors for bone marrow or a heart, and you can get the idea of how amazing this research could be.

These teams are not the first to have created such cells - other studies have created stem cells from a variety of other cells, though some work better than others, and exactly how pluripotent they are is still up for debate. This team created stem cells, called iPS cells, from fibroblasts, the most common cell in connective tissue, from late stage embryos by using a viral vector to introduce genes which allowed the cells to "reprogram" into any cell type.

To prove that these iPS cells really could become anything, they tested them over and over again, including looking at whether they had the same cell surface markers as embryonic stem cells. They used fluorescent staining to show that the created cells did, indeed, have the same markers as embryonic stem cells (Left).

Both groups decided that the truest test of their iPS cells, however, was to attach them to a sham embryo called a tetraploid embryo, which can create a placenta but no actual animal. The only way a mouse would form from the union was if the iPS cells were able to divide and differentiate into the necessary tissues to become a living animal.

The first group, published in Nature, included a dominant black coat color allele into their stem cells, then placed the embryos into white mice, giving them an initial visual check. If the young were black, they had to have come from the stem cells. When the first black baby mouse was born, further DNA tests confirmed that Tiny (as he was named) had indeed arisen from the iPS line. It took them over 250 developing embryos before they achieved a live mouse. Out of the 37 stem cell lines created, 3 produced live mice, and out of a total of 624 injected embryos from the best cell line, they got only 22 live births. That's a success rate of only 3.5%.

Even these mice, though born live, were not all perfect. Some were chimeric, having somehow taken genetic material from both the iPS cells and the host mom or tetraploid embryo. Even those that were fully iPS generated had flaws. Some died just days later, and many were deformed or physically abnormal. 12, however, were able to pass a reproductive biologists strict test of health: they were fertile, producing hundreds of second and third generation mice (like the one on the right). Even still, there is a lot that isn't known about these stem-cell derived mice, like whether their children develop diseases more readily than normal mice, or are as healthy in general.

The other group, who published in Cell, followed the same basic procedure. They were able to create 187 tetraploid embryos and implant them in receptive female mice. Of those, however, they only had 2 live births (1.1%), one of which died in infancy.

Both teams are now looking deeper into the differences between iPS and embryonic stem cells to understand what causes the high mortality, abnormality and failure rates of these embryos. It also remains a mystery as to whether adult fibroblasts can become iPS cells which have the same pluripotent abilities, as both teams used the skin cells from late stage embryos to create their stem cell lines.

If adult cells work, too, it would mean that we might be able to clone adult mammals using their skin. The authors vehemently deny any connection or plans of utilizing this research for human cloning - and at a rate of 1.1%-3.5% just to produce a live birth, let alone further complications, I agree with them. There's still far too much uncertainty to even think of applying this method to humans.

However, the fact that these stem cells were able to be pluripotent, even 1.1% of the time, gives a lot of hope to future medical research. Indeed, we might just be able to create tissues or organs on demand from a patient's own cells in the next 50 years, which would save the lives of many suffering from a variety of diseases. More interestingly, however, is that these cloned animals may lead to a better understanding of how cells develop, divide, and fail, leading to breakthroughs in prevention and treatments of conditions like cancer instead of just patches to prolong life after the disease has set in.

Lan Kang, Jianle Wang, Yu Zhang, Zhaohui Kou, & Shaorong Ga (2009). iPS cells produce viable mice through tetraploid complementation Nature DOI: 10.1038/nature08267

Kang, L., Wang, J., Zhang, Y., Kou, Z., & Gao, S. (2009). iPS Cells Can Support Full-Term Development of Tetraploid Blastocyst-Complemented Embryos Cell Stem Cell DOI: 10.1016/j.stem.2009.07.001

cwilcox Fri, 07/24/2009 - 07:31

Cohabiting with females boosts male fertility

cwilcox — Fri, 23 Jan 2009 03:00:00 +0000

Cohabiting with females boosts male fertility

How many times have you heard a guy say "Women - can't live with them, can't live without them." Well, they just might be onto something. At least kind of. You see, living with a woman might just make you fertile longer. New research published in Biology of Reproduction has found that male mice stay reproductively active longer if they live with a female mouse than if they live alone.

The study, from the University of Pennsylvania School of Veterinary Medicine, sought to see whether living with a female mouse had any affect on a male mouse's fertility as he aged. To do this, male mice were either housed with a female mouse continuously or isolated, given access to a virgin female only at given time intervals to prove fertility (sounds terrible to you guys, I'm sure). They also looked into factors of fertility like testes size and abnormal spermatogenesis at each time point.

They found that male mice which were housed with females were fertile a whopping 20% longer than the isolated males. Also, histological abnormal spermatogenesis appeared earlier in the isolated males, giving a possible mechanism to their sooner decrease in fertility. Interestingly enough, once a mouse started to decline in fertility, the rate at which he became infertile was the same between the two treatments, suggesting that once whatever processes by which a mouse loses fertility begin, they have a set time course.

What does this mean for us? If you want to put off having kids, perhaps having a girlfriend or wife live with you throughout your 20s and 30s will let you have kids later on. Or, conversely, if you live single and alone through those years, you might have a bit more trouble impregnating someone when you're older. It also may explain why males, who some might argue evolutionarily have an advantage by staying single and ready to mingle, form long-term bonds with females. It's possible that the added reproductive benefits of living with the same woman outweigh the costs - while sleeping with different ones and staying a bachelor gets you a few more kids while you're young, the added years of fertility give you more. Albeit that's a bit of a reach (and would require a lot more support), it's possible.

Now, the astute reader would point out at this juncture that the research was in mice, not humans. True, true. But there is the possibility, at least, that this effect could be true for other mammals, including us. Perhaps the most useful application if this phenomena is in other species, however, won't be in our own mating strategies but in the livestock and other breeding industries. Housing a prize stud horse with a nice female might give him a longer reproductive lifespan, meaning a lot more cha-ching for his owner. Or keeping endangered zoo animals with opposite-sexed partners might give struggling population breeding programs an extra boost.

In any case, this new finding might just open up some interesting new studies on the effects of cohabitation on reproduction, and perhaps what pathways this might occur by. And as always, if it's about sex, I'll probably be interested in their findings. I just can't seem to pull myself away from all this reproductive biology. I don't have my mind in the gutter - I swear.

J. A. Schmidt, J. M. Oatley, R. L. Brinster (2009). Female Mice Delay Reproductive Aging in Males Biology of Reproduction DOI: 10.1095/biolreprod.108.073619

cwilcox Thu, 01/22/2009 - 22:00

Mouse Reproduction

Live mice from stem cells!

Cohabiting with females boosts male fertility