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Fully Functional Bioengineered Tooth Grown In a Mouse
A couple of weeks back the Wall Street Journal reported on the first organ grown in vivo from stem cells — a tooth in the mouth of a mouse. Reader cdrpsab spotted the news on the MedGadget blog; the research had been reported earlier in the PNAS. From the WSJ: "The researchers at the Tokyo University of Science created a set of cells that contained genetic instructions to build a tooth, and then implanted this 'tooth germ' into the mouse's empty tooth socket. The tooth grew out of the socket and through the gums, as a natural tooth would. Once the engineered tooth matured, after 11 weeks, it had a similar shape, hardness and response to pain or stress as a natural tooth, and worked equally well for chewing. The researchers suggested that using similar techniques in humans could restore function to patients with organ failure."
Of course, we all grow teeth at the beginning of our lives, but this friend of mine grew a new tooth when he was in his thirties. He had an extraction, and about two years later, a new one came in. He wasn't one of those people who start out with three ranks of teeth (that's pretty rare too, but not quite as rare a growing a new one as an adult. I think his case got written up in some dental journal.
-jcr
The only title of honor that a tyrant can grant is "Enemy of the State."
If you are type 1 then your immune system would destroy any pancreatic islet cells implanted. Type 2 diabetics who are insulin resistant with a burnt out pancreas would be choicer targets for this type of therapy. Type 1 diabetics will be waiting for an immunological solution first.
They're horrible, and I live in the United States, a culture where teeth are perfect and white or you are nothing. My wife has beautiful teeth, and despite the fact that we have nearly identical brushing and dental care habits, my teeth are horrid, yellow, and falling to pieces, hers are beautiful, white, and basically no cavities.
Sorry - not all teeth are created equal.
So here I am, 30-something, fairly affluent, and having horrid teeth. You think I wouldn't hesitate to spend a few Gs replacing my craptastic old teeth with new teeth with zero chance of rejection? Sure, they will go yellow quickly, just like the last ones did, but that means I'm in my 80s or later before my teeth are in any way unusual. And effectively, that means good teeth for life.
I've been waiting for this kind of treatment. Where do I sign up?
I have no problem with your religion until you decide it's reason to deprive others of the truth.
The problem with growing organs is that in order to get cells to multiply you have to disable certain genes in those cells, or at least reset their counters. Which genes ? Well those that guard against cancer ...
Our bodies go to great lengths to prevent cells from multiplying anywhere and it is only allowed by the human DNA in very specific cases : blood production in the bone marrow, when a woman becomes pregnant, and just before a woman gives birth. There are others, but those are major modifications of human cell's normal reproduction. The body goes to great lengths to prevent cell division in organs once a human being is born, instead choosing to do the bulk of the necessary divisions before birth and then letting those already-existing cells enlarge instead of divide to make a child grow. That's not to say there is no cell division involved in growing a child, but a lot less than you'd think from the size difference.
All 3 of those exceptions are also major causes of cancer : leukemia, endometrial cancer and breast cancer.
Getting stuff to grow is easy, just kill of the p70 gene. Getting stuff to grow safely is hard. Very very hard. Loads of research still need to be done before this can really be risked in a live human being.
As a Type 1 diabetic myself it really makes my day when something new and cool like this pops up on my screen. I vaguely remember some doctor-or-some-such saying a few years back that diabetes is a disease that should have been cured (or at least fixable) 30 years ago. If not for the fact that medical companies have an income from insulin, needles, and other paraphernalia as stable as WoW subscriptions and probably a goodly bit bigger, it probably would have. Though I am pleased to see there have been actual, tangible improvements made in the few years I've lived with this damned malfunction, it scares and annoys the hell out of me that all the big money goes into making a disease/malfunction that kills more people than either cancer or AIDS a bit more manageable instead of fucking fixing it.
Fix 1 (don't know the current status of gene replacement therapy, but seems doable):
Why can't they just get the DNA of some thousand diabetes type 1 patients and healthy people on record, analyze it for the bits that stick out in diabetics, and use a virus to replace the defect bits? Isn't this the general idea behind gene replacement therapy? Follow up with auto-immune drugs used for transplant patients so we get rid of all the T-cells made for killing insulin producing cells, and transplant/grow a pancreas. I don't know.. it seems so god damned simple, yet IAJARG (I Am Just Another Random Geek) so I'm probably wrong.
Fix 2 (bit of a hazzle, but uses everyday techniques that any semi-large hospitals should have expertise on):
What about this? Transplanted organs are rejected by the auto-immune system. The little bastards are produced in the bone marrow (right?). This would mean that if my entire auto-immune system is wiped clean (with drugs every hospital has) and my bone marrow is replaced with donated marrow from a healthy person, I would in effect have that persons auto-immune system. As far as I can see, the new bone marrow isn't going to reject itself. It might reject the entire body it has been transplanted into but blood cancer is one of the least fatal cancers these days, right? Bone marrow transplant can't be that dangerous..? Again, transplant a pancreas (preferably from the same donor) or grow a new one. A couple of years of vaccinations and being sick and on antibiotics 24/7 later.. Voila, defective auto immune system is out, new one is up and running, new pancreas is in and the damned immune system doesn't attack it!
Could someone smarter than me please inform me why a disease, seemingly so simple to fix, remains uncured to this day with no big breakthroughs on the up-and-coming? Everyone gets their dose of daily cancer/AIDS/COPD/anti-drug propaganda. Everyone gets a visit now and then from someone collecting money for cancer research projects. At the same time, most people I talk to think diabetes means I have to take one shot a day (or a few pills) and the reply to how serious a condition it actually is usually boils down to "You can die from diabetes..? *disbelief*", "You sure you aren't making that up?" or "LOL, why haven't I ever heard of anyone dying of it then?".
Different people have different "strengths" of immune reaction. I've been diagnosed T1 diabetic for over a year now (and had symptoms for quite a while before I was diagnosed), and I am either incredibly sensitive to injected insulin, or my body hasn't quite managed to totally kill of my pancreas yet. Some people go from perfectly healthy to a coma in a matter of weeks, others like me can last much longer; If it has taken my body this long to destroy my pancreatic islet cells, then maybe a "top up" every year or so may do just about enough to push my pancreas to produce enough insulin to give up the injections.
T1 diabetics sometimes get pancreas transplants. I believe that sometimes the islet cells give up within a matter of months, other times an individual may be free from insulin injections for a couple of years [citation needed]
I also seem to remember an article about a female professor at a British university who cured rats who's pancreas had been removed. I can't for the life of me find the article, but the process as described consisted of treating the rats with one common drug that kills white blood cells and another drug that had a less-known side effect of somehow making the auto-immune system not produce the beta-cell attacking basta.. *cough* cells.
This research was done to find a way to prepare a patient for transplant and stop the auto-immune system from immediately destroying the new pancreas. To her great surprise, it seems the spleen produced or released stem cells of some sort that started producing insulin. The rats only needed to stop producing the hostile white blood cells after which they fixed the missing beta-cells themselves.
In light of this, I want that god damned bone marrow transplant, in effect getting someone else's auto-immune system. Has this been tried on diabetics? Has any positive changes been observed, f.ex. in a diabetic patient treated for blood cancer?
My ex was a biologist, and told me that the way the healing of wounds is implemented is that cells multiply when there aren't other cells next to them. If there is a hole, then the cells will divide to fill in the gap, with the signal to stop occuring when the dividing cells finally close up the hole. The problem is that that signal to stop gets screwed up somehow sometimes - either it's not produced, or its ignored. There is only a small probability of this happening, but if you are repeatedly wounded, then the probability increases. Some people have a habit of biting the insides of their cheeks. I understand that doing so can cause cancers where you bite.
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"Which genes ? Well those that guard against cancer ..."
Which brings up an interesting point... Since our lives depend critically on the controlled death (apoptosis) of cells. A lot of people don't fully grasp that controlled death of cells is absolutely critical to maintaining limb, bodily form, and organ integrity (eyes, hands, creating fingers)
You can see what happens here when when apoptosis goes wrong:
http://en.wikipedia.org/wiki/File:Celldeath.jpg
Thank goodness for controlled cell death.
I can see Toonol's worries here. The ovaries contain single cells that ought to grow into a whole being when fertilized. Sometimes, these go wrong, and you get something else. These other things are usually hair, teeth, or occasionally eyes (eeww!). However, you don't get a fingernail or a kidney or a brain. This is probably because hair, teeth and eyes can be 'seeded' from a single cell, where other organs probably develop from a coordinated modification of a set of cells.
This is not to say that there isn't come magic genetic 'sudo' command that allows you to ask for a left kidney, medium size, but we haven't seen any sign of it yet.
No, I don't have diabetes, but my girlfriend does. Believe me, I understand that it can be miserable and painful. And I also know about multitude of complications resulting from diabetes (like feet rotting and falling off or kidney diseases).
Transplantation of the whole pancreas is possible. It's actually routinely performed right now. However, bear in mind that 1 year survival is about 95% and 10% patients still have to use insulin injections even after transplantation. And don't forget lifetime use of immunosuppresants.
Refilling a blown tire might be a good analogy for some proposed treatments. An injection of islet cells once a year might be much more tolerable than the life of continuous immune suppression.
Perhaps we can't "seed" a more complex organ such as a kidney, (Although I thought that eyes were pretty damn complex organs, what with the lenses and rods and cones and such.) but perhaps through study we can come to understand the more complex interactions of genomes that creates a kidney or a liver and one day grow replacement parts without the ghoulish proposition of cloned complete human "parts farms".
Of course, we all know that most of the research is going to end up in the breast augmentation and hair replacement fields anyway, so I guess we needn't worry too much.
Official Heretic from the "Church of Global Warming". Proven right thanks to whistle blowers. AGW = Flat Earth Theory
Note that the text hasn't been updated since ~2005 and their initial human trial was, according to them, a success. To a diabetic, a staggering, mindblowing success! Apparently, the islets were injected subcutaneously whereupon they went on to regulate the test subjects blood glucose levels for up to 20 months, without long term immunosuppression! Why am I not receiving this treatment right now? Can I sue the Norwegian government for attempted murder? =(
Yes, yes, availability of spare parts etc. Screw that. Abolish religion's hold on law and politics and enforce organ harvesting from anyone declared dead possessing spare parts of value to someone still living.
Quite an arrogant thing for you to say (assuming that you, for the sake of validity of your argument, would have told us if you actually have diabetes).
It may be arrogant, but they are, in my opinion, right. If you put effort in to actually controlling diabetes, you should be able to avoid complications for most of your life. I know a couple of diabetics with T1 for over 40 years and no complications; I have spoken with diabetics who have had it for over 50 years with minimal complications. These are people that, initially, could only test their urine for glucose, they had no idea what their blood sugar was doing, and they had horrible peaky insulins which made it difficult to prevent lows/ highs. Why can't we achieve the same thing with infinitely better glucose monitoring and insulin with vaguely sensible action profiles? Why spend years of your life in pain with a series of procedures that may not work (and might even kill you) to try to prevent complications that may not even happen if you control your diabetes correctly?
I, for one, think that regular "top ups" of islet cells produced with the patients own genetic material is the way to go.
Getting stuff to grow is easy, just kill of the p70 gene. Getting stuff to grow safely is hard. Very very hard. Loads of research still need to be done before this can really be risked in a live human being.
would you care to give a reference for p70 being used to create iPS (induced pluripotency)? As far as I am aware the genes typically used are oct-4, sox2, c-myc, nanog, lin28, klf4 and p53 (both p53 and c-myc are oncogenes, the rest are not) Interestingly a paper was published a few months ago which describes a method for transient expression of these genes. This eliminates (or at least greatly reduces) the risk of cancer arising from stem cell treatment as the expression of any oncogenes is only long enough to revert the cell back to a pluripotent state.
Retroviral treatment sometimes works. The problem is we don't have any way of telling where to put the genes we're inserting, and if they insert in the wrong place, the cell could do nasty things: become cancerous, start pumping out odd hormones, start pumping out herpesvirus, are a few that come to mind. It can be done, and has been done, but it's not easy.
Replacement of the entire auto-immune system is really difficult. People have done this experimentally. I worked on a project that was curing feline leukemia virus by doing this. We had a 30% cure rate, a 10% failure rate (cat ended up dying of FLV anyway), and a 60% mortality rate. The problem is that it's very difficult to kill off 100% of the patient's immune system without killing the patient, and if there's anything left, then you have an immune system sumo fight inside the person's body. Growing a new pancreas is absolutely the best option, and people are working on exactly this, very hard. The main problem is that it's difficult to get larger, more complex organs to grow because they rely on adjacent tissues to get their structure right -- it's a fractal sort of process. So unless you grow the whole body, it's hard to do. But (as someone else mentioned) building what amount to micro-pancreas structures in small encapsulated chunks and putting them in the body, seems to be a good approach. I think Type I diabetes will be fixed within 15 years. It's easier than Type II. But it's still not easy.
Nostalgia's not what it used to be.
You are seriously underestimating the potential of graft versus host disease. Seriously. You do not want to eliminate your own immune system only to get a whole new one which will recognize your body as foreign.