Stem Cells and Sex Change

[Ilya Muromets]

Just a question that's been bugging me recently. Now, as I understand it, stem cells possess the potential to differentiate into other more specialized cells. Get enough to turn into said specialized cells and you could theoretically have new tissue. More of that, and you could potentially grow organs. At least, that's how I understand it. If I'm mistaken, then please correct me.

Now, I know stem cell research still has a really long way to go before we even come close to anything even remotely resembling that. However, what I want to know is whether it could eventually contribute to sex change operations that actually create fully functional sexual and reproductive organs. Is it possible, at least in theoretical eventuality, to actually use stem cells to essentially grow such organs?

[Knife]

I really don't see why not, but I don't see why you'd want that for the grand scheme of the question. Sex organs are already derived from the same tissue, only with different hormone triggars at certain stages. The tissue that makes the penis is exactly the same tissue that makes the clitoris, the same tissue that makes the labia is exatly the same tissue that makes the scrotal sack. They are not totally different tissue and/or organs in and of themselves.

I can see the utility of what you propose, as easier for the surgeon to hack off the old bit and sew on the new, instead of reconstructing out of what it there. IDK, functionality might be better, but then you run into hormone problems, unless you use the technique to adjust hormones and endo/exocrine function. Also there are structual differences in the cerebral cortex, not sure how you'd even tackle that.

[Broomstick]

Interesting question.

A lot depends on manipulation of genetic instructions.

And XY embryo will, to a degree, default to female appearance IF you prevent testosterone from affecting it - either via genetic defect or not permitting the hormone into the cell culture. So... if you could get XY stem cells from a donor to differentiate into the proper cells to form a vagina and other external female organs and not add any male signaling hormones you could get a vagina you could later transplant into the donor. For XX stem cells, you could again differentiate the cells into the precursor of a penis, add the proper hormones, and get a penis or reasonable facsimile.

Then all you have is the "mere" problem of transplanting the new organ into the donor and getting all the nerves hooked up to make it functional. Particuarly for female to male transexuals, this has the potential to be a great improvement over current surgical "solutions", but there are some significant hurdles to cross.

In either case, the above would not generate functional reproductive organs, "just" sexual organs. There are some naturally occuring people who are XX males that may be able to reproduce on their own (since they are physically indistinguishable from XY males they are likely to go entirely unnoticed in most cases, barring chromosome analysis. Since many that have been discovered are, apparently, sterile, "fully functional" is not a guarantee here) which means it might be feasible to induce XX cells to produce fully functional, sperm-producing testis although such a man could only father girls. Getting XY cells to produce eggs in an ovary might be more challenging, and a Y egg would not be viable (0Y and YY genotypes always die before birth) their fertility would be less than normal.

So, I'd say the potential is there, but it won't be the first thing with do when we get pluripotent stem cells we can grow into viable organs.

[Eulogy]

Of course, this can also be used to say, reverse castration or genital mutilation. Rejection issues, however, will not be solved until we get genetic enginerring.

[Shroom Man 777]

That begs an interesting question, though.

Can you transplant to a person an organ that he or she does not originally have? Even if the blood type, or even the DNA, matches the recipient - if you give a man a vat-grown uterus, or a woman a vat-grown penis - would there still be rejection?

And, uh, I've always wondered. In normal sex change operations, can the restructured genitalia actually... feel anything?

Cause if not, then maybe sex change through the creation of "real" genitals via stem cells would be a superior alternative?

but then you run into hormone problems, unless you use the technique to adjust hormones and endo/exocrine function. Also there are structual differences in the cerebral cortex, not sure how you'd even tackle that.

The person can take hormone supplements to better facilitate the sex change, as done in real life for men who want to grow bleeding breasts and stuff.

[Psychic_Sandwich]

Can you transplant to a person an organ that he or she does not originally have? Even if the blood type, or even the DNA, matches the recipient - if you give a man a vat-grown uterus, or a woman a vat-grown penis - would there still be rejection?

If it's grown from their own cells? No. The epitopes used to determine self from non-self are all things like glycoproteins so on (that is, they're all dependant on DNA, rather than environmental factors), and if the cell is grown from your own tissue, all of those will identify as 'self'.

[Broomstick]

That begs an interesting question, though.

Can you transplant to a person an organ that he or she does not originally have? Even if the blood type, or even the DNA, matches the recipient - if you give a man a vat-grown uterus, or a woman a vat-grown penis - would there still be rejection?

No.

If the immune system markers, which are controlled by genes, are the same there are no rejections. We see this in identical twins where, of course, an organ can be transplanted from one to another with no rejection issues whatsoever. Assuming you started with the donor's own cells and did not change anything to do with immune markers (totally unnecessary for this) then it would in essence be no different than transplanting an organ from one identical twin to another.

For several years now we have had the capability to culture human skin from the planned recipient's own cells. There has also been at least one artificially cultured bladder that was grown from a patient's cells and transplanted into the subject. No rejection problems There are some other issues, but rejection is not one of them.

And, uh, I've always wondered. In normal sex change operations, can the restructured genitalia actually... feel anything?

To greater or lesser degree, yes. For male to female, tissue from the penis is used to construct a vagina and provided nerves aren't severed there will still be feeling in the new configuration. The female to male operation is a little more involved (not to mention lacking in natural erection abilities, though there are work arounds for that) and probably more likely to result in complications leading to diminished sensation. If all goes well the transsexual will continue to have sensation in his/her genitals. If there are complication sensation may be lost.

Cause if not, then maybe sex change through the creation of "real" genitals via stem cells would be a superior alternative?

Consider the problem of a hand transplant. Although nerves are connected between the recipient and the donor hand such that, with time and some good fortune, some sensation and movement will be had the newly attached hand will never have normal sensation or dexterity. It's certainly better than no hand (well, maybe not - one recipient did request to be reamputated) but it's not a normal hand either. Presumably, with this sort of transplant, one would have functional genitalia that still did not have quite normal sensation or function. For female to male transsexuals, where the current methods are not particularly wonderful in result, this may or may not be a net gain. One benefit may be a penis that can have natural erections and does not require grafting of tissue from elsewhere in the body (which present methods do) which can lead to scarring and various complications. For male to female transsexuals, though, current methods may continue to be superior as, ideally, the nerves are never severed and blood supply to the tissues is never interrupted.

[Lord of the Abyss]

I really don't see why not, but I don't see why you'd want that for the grand scheme of the question.

The ability to carry a child with one's very own uterus ? Or produce your own eggs or sperm? Although the latter would require the ability to insert Y chromosomes if you wanted male children to be possible.

[Junghalli]

In either case, the above would not generate functional reproductive organs, "just" sexual organs. There are some naturally occuring people who are XX males that may be able to reproduce on their own (since they are physically indistinguishable from XY males they are likely to go entirely unnoticed in most cases, barring chromosome analysis. Since many that have been discovered are, apparently, sterile, "fully functional" is not a guarantee here) which means it might be feasible to induce XX cells to produce fully functional, sperm-producing testis although such a man could only father girls. Getting XY cells to produce eggs in an ovary might be more challenging, and a Y egg would not be viable (0Y and YY genotypes always die before birth) their fertility would be less than normal.

If you're talking about androgen insensitive males there, IIRC they are always sterile (barring being able to artificially extract viable sperm from their undescended testes). They have undescended testes in their abdomen and no ovaries or uterus.

Getting a functional ovary out of XY cells would probably not be impossible, with sufficient technology. Males have all the same genes that females do, and that includes the genes that govern ovary development and function. It's a "simple" matter of activating and deactivating the right genes (note quotation marks, as I'm not saying that's simple simple if you get what I mean). Getting functional testes from XX cells might be a good deal harder, as XX cells lack the SRY testicle-formation gene which is on the Y chromosome. You'd probably have to replace one of the X chromosomes with a Y chromosome, making the person a genetic chimaera when you implant the cultured testes. This might or might not create rejection issues, I really don't know.

[Ilya Muromets]

Consider the problem of a hand transplant. Although nerves are connected between the recipient and the donor hand such that, with time and some good fortune, some sensation and movement will be had the newly attached hand will never have normal sensation or dexterity. It's certainly better than no hand (well, maybe not - one recipient did request to be reamputated) but it's not a normal hand either. Presumably, with this sort of transplant, one would have functional genitalia that still did not have quite normal sensation or function. For female to male transsexuals, where the current methods are not particularly wonderful in result, this may or may not be a net gain. One benefit may be a penis that can have natural erections and does not require grafting of tissue from elsewhere in the body (which present methods do) which can lead to scarring and various complications. For male to female transsexuals, though, current methods may continue to be superior as, ideally, the nerves are never severed and blood supply to the tissues is never interrupted.

Couldn't the nerve and blood vessel connections be re-grown as well, though? From what I can tell, one of the hopes for stem cells is they can re-grow damaged tissue. Could that also apply to this as well, or are there are great difficulties in that area?

[Shroom Man 777]

There are great difficulties in that area. Nerves are delicate things and "connecting the wires" would be something requiring a lot of precision.

No.

Ah. There's no reason for rejection if a transplanted organ genetically matches the recipient. I was just wondering if it would be the same if the recipient never originally had that particular organ. But it's just a piece of meat, and if the meat matches the recipient, then there'd be no reason for rejection.

[Junghalli]

Just wondering, would there be potential rejection issues with, as I said, implanting testes grown from stem cells with one of the X chromosomes replaced by a Y chromosome in an female-to-male transsexual? Would the body recognize an organ that's genetically identicle except for having an XY karotype instead of an XX karotype as a foreign intrusion?

[Broomstick]

In either case, the above would not generate functional reproductive organs, "just" sexual organs. There are some naturally occuring people who are XX males that may be able to reproduce on their own (since they are physically indistinguishable from XY males they are likely to go entirely unnoticed in most cases, barring chromosome analysis. Since many that have been discovered are, apparently, sterile, "fully functional" is not a guarantee here) which means it might be feasible to induce XX cells to produce fully functional, sperm-producing testis although such a man could only father girls. Getting XY cells to produce eggs in an ovary might be more challenging, and a Y egg would not be viable (0Y and YY genotypes always die before birth) their fertility would be less than normal.

If you're talking about androgen insensitive males there, IIRC they are always sterile (barring being able to artificially extract viable sperm from their undescended testes). They have undescended testes in their abdomen and no ovaries or uterus.

When I mentioned XX males I meant XX males - men who are physically male but with two female X chromosomes. What apparently happens is that the genes from the SRY regions "jump" from a Y to an X chromosome during sperm formation, resulting in an X chromosome with a few additions. Depending on how many genes make the journey, and which one, the individual in question may be somewhat effeminate or may be indistinguishable visually from any other male human being. Typically it is discovered when said person shows up with a complaint of infertility. It is believed these people are all infertile but it is not inconceivable that somewhere and somewhen the proper genes for sperm production make the jump to an X but since a person who does manage to father children wouldn't show up complaining of infertility and we don't routinely investigate people's chromosomes for no reason such a person would be undetected.

XX males are separate and distinct from XY females, the XY females being where the body doesn't react to androgens. XY females are women, albeit they tend to be tall and lack armpit and public hair as well as failing to menstruate (not having a uterus). XX males are men, you wouldn't mistake them for anything else, they do have things like armpit hair and beards and a working penis although they also have a higher rate of things like gynecomastia than the XY male population and they tend to be short, the height of XX females of their ethnic group.

Here is a case report complete with picture discussing one such instance. A Google search easily brings up more cases. The phenomena was only first described in 1972 and appears less common than, say, Klinefelter's Syndrome (XXY or XXXY or other similar variants). Then again, there are probably quite a few of these guys out there who are simply never discovered.

Getting functional testes from XX cells might be a good deal harder, as XX cells lack the SRY testicle-formation gene which is on the Y chromosome.

As I mentioned, for XX males the SRY genes are translocated to an X chromosome (or, possibly, some other chromosome). Something like 10-20% of XX males don't seem to have an SRY region, but although important they aren't the only genes that play a role in turning out a male body.

You'd probably have to replace one of the X chromosomes with a Y chromosome, making the person a genetic chimaera when you implant the cultured testes. This might or might not create rejection issues, I really don't know.

It might result in rejection issues. One reason that vasectomy reversals don't always work is because men can and do create antibodies to their own sperm simply because, with only half the normal number of chromosomes, the body does not recognize the cells as self and the immune system sets out to destroy them. Vasectomies increase the chances of this because the cut ends of the vas deferens can result in sperm going where normally they don't, but autoimmune rejection of sperm can occur even in intact males, it's just a lot less common (which is a good thing for the continuance of the species).

[Wyrm]

Just wondering, would there be potential rejection issues with, as I said, implanting testes grown from stem cells with one of the X chromosomes replaced by a Y chromosome in an female-to-male transsexual? Would the body recognize an organ that's genetically identicle except for having an XY karotype instead of an XX karotype as a foreign intrusion?

The immune system doesn't directly recognize genetics. What it recognizes is are antigens, compounds that bind to the MHC proteins encoded on chromosome 6, an autosome. If a protein made by the foreign Y binds to the MHC protein and the complex is then presented to the immune system, our female-to-male transsexual would be in trouble. However, if these unfamiliar proteins do not bind, or production is stopped prior to implantation (likely, since the SRY gene is only active for a short time), our friend has a fighting chance of never suffering any ill effect... other than those implied by having a pair of nuts.

[Starglider]

There are great difficulties in that area. Nerves are delicate things and "connecting the wires" would be something requiring a lot of precision.

Medical applications aren't my field, but over the last two decades research neuroscientists have been making steady progress in improving electrode array placement techniques. It would not surprise me if a cybernetic interface (implanting two electrode arrays and some drive electronics, probably organically powered) becomes the preferred solution even when connecting a fully organic replacement limb. That also provides scope for using digital signal processing techniques to hasten the adaptation/relearning process.

[Knife]

I really don't see why not, but I don't see why you'd want that for the grand scheme of the question.

The ability to carry a child with one's very own uterus ? Or produce your own eggs or sperm? Although the latter would require the ability to insert Y chromosomes if you wanted male children to be possible.

But as pointed out, it's more than sewing on the new part. Nerve and blood capillary connections just to get it *working* then as with most organs, supporting organs being adjusted. It's not a plug and play type of scenario.

[Justforfun000]

But as pointed out, it's more than sewing on the new part. Nerve and blood capillary connections just to get it *working* then as with most organs, supporting organs being adjusted. It's not a plug and play type of scenario.

Yes, you have to remember we are talking about living tissue and any kind of injury, whether caused by a knife, fire, etc....can heal yes....but it also creates scar tissue. Or to put it another way as a clever quip I heard said in referring to why Jesus resurrected with the evidence of his crucifixion in his hands and feet? (surprisingly so for a religious point)...You can pull out the nails, but you can't pull out the nail holes.

Until they can advance to the point where extreme microsurgery is possible with 100% regenerative healing, or to the other extreme....cloning becomes a reality...we can not just stick things together in the human body and expect perfect function. Nice idea...hard reality.

[The Duchess of Zeon]

Scar tissue can be extremely minimized when you really try, from ridiculously invasive and massive surgical procedures. I know this from first hand experience, of course. I could go into extensive details about how it's minimized in the current procedures and prevented from interfering with nerve processing, but I don't think it would be particularly relevant to the thread. It's wrong, though, to imagine that the current procedures are insufficient. Rather short of direct genetic manipulation to create full fertility it's really close to about as good as we can get, already. I can only thing of two major improvements, one would be finding some way to eliminate scar tissue entirely, the other one is fairly subjective.