Maurie Hill's Story in PLoS One
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    Maurie Hill's Story in PLoS One

    1. #1
      Iarons's Avatar

      Maurie Hill's Story in PLoS One

      OK, I've found the new Ricki Lewis blog entry about Maurie Hill in PLoS One.

      I haven't read it yet, but here's the link.

      More after I read the writeup -- it is rather long, so I haven't tried to reproduce it here.

      I'll leave that to someone else.

      Irv

    2. #2
      GMAN's Avatar
      Human Embryonic Stem Cells Finally Reach Clinical Trials: Maurie’s Story

      By Ricki Lewis, PhD
      Posted: September 27, 2012


      On July 11, Wills Eye Institute ophthalmologist Carl Regillo delicately placed 100,000 cells beneath the retina of 52-year-old Maurie Hill’s left eye. She was rapidly losing her vision due to Stargardt disease, an inherited macular dystrophy similar to the much more common dry age-related macular degeneration (AMD).

      Maurie’s disease was far along, the normally lush forests of photoreceptor cells in the central macula area severely depleted, especially the cones that provide color vision. Would the introduced cells nestle among the ragged remnants of her retinal pigment epithelium (RPE) and take over, restoring the strangled energy supply to her remaining photoreceptors? They should, for the cells placed in Maurie’s eye weren’t ordinary cells. They were derived from human embryonic stem cells (hESCs).

      I’ve waited 15 years to see human embryonic stem cells, or their “daughter” cells, make their way through clinical trials. And thanks to Maurie’s sharing her story, I’m witnessing translational medicine.
      On September 29, 1997, The Scientist published my first stem cell article, Embryonic Stem Cells Debut to Little Media Attention. Alas, the public was still too enamored with Dolly the cloned sheep to pay much attention to cells that could both spawn specialized cell types and “self-renew,” maintaining a perpetual stream of hard-to-derive cells that could be used to both observe embryonic development and replace abnormal adult tissue. Over the years, public interest seemed to surface only on slow news days. And still the media report that the cells can “turn into” every cell type in the body – ignoring the very quality that defines the cells: the capacity for self-renewal, making more of themselves as their daughters specialize.

      Partly because deriving hESCs until just a few years ago required destroying early human embryos, research using less objectionable stem cells accelerated. And while so-called “adult” and induced pluripotent stem cells (iPSCs) don’t require embryos and match patients so that the immune system isn’t provoked, embryonic stem cells remain the “gold standard” for scrutinizing a disease’s beginnings as the ball-of-cells early embryo folds into layers, contorts, develops organs, and grows. For example, hESCs recently glimpsed how the drug thalidomide harms embryos. The second use of hESCs is to generate useful specialized cells, such as sensory neurons to restore hearing. It’s this second application – hESCs as a source of implants – that is the focus of clinical trials for Stargardt disease and dry AMD.

      Using hESCs could be incredibly economical. Just one can yield many millions of cells, the characteristics of the cells coaxed by the cocktails that researchers choose. And embryos can be returned to the freezer, unharmed. The RPE cells in Maurie’s eye came from an hESC line derived in 2005 by Robert Lanza and colleagues at Worcester, Mass.-based Advanced Cell Technology, one of five cell lines called NED for “no embryo destroyed.”

      NED cells come from a protocol similar to preimplantation genetic diagnosis (PGD), in which one cell of an 8-celled embryo is sampled to screen for genetic disease, and if all is well, the remaining 7-celled embryo is implanted in a uterus. PGD has been around since 1989. The ability to pluck out a cell at this stage without damaging the whole is a characteristic of our branch of the animal kingdom called indeterminate cleavage, for those who recall Zoology 101.

      For a time, the first clinical trial to use hESC-derived cells — oligodendrocytes to treat spinal cord injury – was sponsored by Menlo-Park, CA–based Geron Corp. That effort ended in November 2011, due to cost. But eye diseases are perhaps a better first choice, because the retina is naturally shielded from the immune system.

      I never expected to befriend one of the first people to be in an hESC clinical trial. But this past June, an email friend connected Maurie and me. She and her older sister Cindi would soon be on their way back from the Wills Eye Institute in Philadelphia, where they were being evaluated for the clinical trial to treat Stargardt disease. They’d be at the Albany Amtrak station on their return to Vermont, near my home.

      The sisters have become so adept at using their peripheral vision to see around the central abyss in their visual fields that I couldn’t, at first, tell that anything was wrong with them. They were as excited as if they’d just won the lottery.

      “Twelve people are participating. When I saw something about the clinical trial a year ago I thought yeah, right. But things just lined up,” Maurie said. She works 12 hours a week blogging for Ai Squared, maker of ZoomText software, and has a young daughter, a husband, and an associate’s degree in electronics and engineering technology.

      Cindi agreed. “I was thinking this will never happen. There were too many barriers, too many things had to fall into place.”

      The visual loss of Stargardt is slow. “In 3rd grade I‘d read very fast, but by 5th, I knew I should be able to read faster,” Maurie recalled. She struggled, not realizing anything was wrong, and didn’t even have an eye exam until her physical for college. “The doctor saw something and he sent me to an eye specialist who sent me to another eye specialist, but still I had no diagnosis.”


      Eyechart: This is what Maurie Hill sees with her right eye covered when observing the eye chart from a meter away. (credit: Derek Bove)


      At age 30, Maurie needed a physical for work, and again made the rounds of referrals. “I could still see pretty well, but some things bothered me: night driving and the lights coming at me and then disappearing, and being unable to recognize faces. I’d have trouble going from light to dark and vice versa.” By age 35, yet another job required a physical, and she went again to retinal specialists, but by this time she’d lost enough visual function to meet the diagnostic criteria for Stargardt. With every month, she could see less.

      Meanwhile, Cindi’s vision was going downhill. “I went to my doctor, and I said ‘my sister has this, do I have it too?’ He ran out to open his textbook to see what it was, and said ‘yes, I think you have it,” Cindi said. She taught special ed for 14 years before she had to leave, no longer able to do the visual tasks required for her job, even with the adaptive technology that had helped for a decade.
      The sisters have four other siblings. True to Mendel’s first law for single-gene inheritance, their older brother has Stargardt too, although his case is so mild that until recently he could read normal-sized print, although slowly and with great eyestrain.

      In 2009, the siblings heard about successful gene therapy for Leber congenital amaurosis another inherited retinal disease. Could they have gene therapy too?

      In May 2009, the family went to the National Eye Institute to confirm Maurie’s 1995 diagnosis, which had been based on clinical findings. But genetic test results indicated that the family didn’t have a mutation in the ABCA4 gene, as 40% of those diagnosed with Stargardt do, or any other mutation. “That was a little disappointing, since we knew the mutation would have to be known to do gene therapy,” recalled Maurie.

      But what about stem cell therapy?

      Maurie read (by zooming her text and using her peripheral vision) a news release from Advanced Cell Technology announcing that their researchers had derived RPE cells from hESCs. The first two applications would be dry age-related macular degeneration and Stargardt disease. Mice and rats had responded well.

      So Maurie called her siblings, and her brother called ACT immediately, but got nowhere. The timing just wasn’t right.

      By late 2010, FDA had approved ACTs testing the RPE cells for safety, and clinicaltrials.gov officially announced the upcoming experiments in late April 2011. Four cohorts of three Stargardt patients each would receive escalating doses, starting with 50,000 RPE cells. The AMD trial would proceed in parallel.
      Results came very quickly, published online in January 2012’s Lancet. And the news was good. The cells hadn’t harmed the first two patients, a woman in her 70s with AMD and a 51-year-old woman with Stargardt, both treated at the Jules Stein Eye Institute in Los Angeles.

      A fear of using embryonic stem cells is that they can give rise to teratomas, which are bizarre tumors festooned with bits of specialized tissue such as teeth and hair. If an ES cell lurked among the RPE cells put into a patient’s eye, a teratoma might sprout. But since this hadn’t happened by three months, and neither woman had inflammation or immune rejection, the therapy passed the first safety hurdle. (A year out, the 9 patients treated so far report more vibrant color vision and improved visual acuity. The first woman treated, for example, could detect only hand-waving before the procedure, but can now read three lines on an eye chart.)

      After the sisters heard the two LA patients on NPR January 23, Maurie called the clinical trial director at the nearest participating center, the Wills Eye Institute. When she finally got through, she learned that the center would consider only local patients, so they’d be easier to follow. But a month later, her local eye doctor urged her not to give up.

      So Maurie called back, and finally the timing was right. “The research coordinator answered and was flowing with information.” Elated, Maurie sent her medical records right away – she had fortuitously just had a colonoscopy (cancer is grounds for exclusion due to the teratomas), mammogram, Pap smear, cholesterol test, and more.

      Dr. Regillo liked Maurie’s test results. She was the ideal clinical trial participant – healthy except for the condition under study, a rarity. When Maurie got the good news, she asked if she could bring Cindi along. Both sisters agreed to foot the Amtrak bills. They told me about the visit when I met them in the Albany train station. Maurie was in; Cindi is still being evaluated.

      The big day came in just a month. On July 11, Maurie and Cindi arrived a little before noon, surprised at the video cameras. Every step of the procedure had been meticulously choreographed and practiced, with trial runs to identify the time with the lightest traffic on a midsummer Wednesday between New Jersey, where the precious cells were on ice, and Philadelphia.

      The cells arrived in a red cooler, the clock ticking down the 3 hours they could survive. Testing for viability and contamination took 30 minutes, and then the procedure itself took just 3 minutes.
      Maurie hadn’t expected to be awake and aware as the descendants of human embryonic stem cells flooded her eye, although she’d chosen local anesthesia. “I actually saw the needle come in the inside of my eye! Dr. Rigello said, ‘Can you see that?” I said I clearly saw the needle coming in from the left, and he said, ‘Yup!’ I could see the fluid coming out and forming a little puddle. It was the coolest thing. And everyone was so excited that I saw it!”


      Maurie Hill, shortly after having 100,000 retinal pigment epithelium (RPE) cells derived from human embryonic stem cells (hESCs) placed in her left eye


      And so Maurie Hill joins the brave and selfless individuals who have volunteered to participate in clinical trials, who make new treatments possible for many. But Maurie’s going one huge step farther: she’s blogging about her progress.

      To be continued …
      Last edited by GMAN; 09-27-2012 at 12:33 PM.
      DMSOB, stemedga, TORCH and 19 others like this.
      "Those who are able to see beyond the shadows and lies of their culture will never be understood, let alone believed by the masses" Plato


    3. #3
      Iarons's Avatar
      Thanks, GMAN, I was just about to post it after reading it.

      I've already sent congratulatory emails to both Ricki and Maurie. I think Ricki did a marvelous job in telling both Maurie's story and ACT's story about the trial.

      Irv

    4. #4
      GMAN's Avatar
      Quote Originally Posted by Iarons View Post
      Thanks, GMAN, I was just about to post it after reading it.

      I've already sent congratulatory emails to both Ricki and Maurie. I think Ricki did a marvelous job in telling both Maurie's story and ACT's story about the trial.

      Irv
      Irv what about the line about Maurie receiving cells from NED lines???
      dyooperya likes this.
      "Those who are able to see beyond the shadows and lies of their culture will never be understood, let alone believed by the masses" Plato


    5. #5
      Iarons's Avatar
      Quote Originally Posted by GMAN View Post
      Irv what about the line about Maurie receiving cells from NED lines???
      Ricki should know -- she's researched this field thoroughly.

      Irv

    6. #6
      Regenerative Guru Member Actc_fan's Avatar
      Quote Originally Posted by GMAN View Post
      Irv what about the line about Maurie receiving cells from NED lines???
      GMAN,

      My understanding is:
      - There are 4 NED lines (NED-1 through NED-4), where the hESC was derived WITHOUT EMBRYO DESTRUCTION, and the embryo was NEVER destroyed.
      - MA09 is an NED line, in that the hESC was derived WITHOUT EMBRYO DESTRUCTION, BUT, the embryo was destroyed after the process.

      So technically, creation of MA09 did not cause embryo destruction, but ACT has to be careful when stating this.

      Anyone please correct me if I am wrong. Thanks
      Last edited by Actc_fan; 09-27-2012 at 01:03 PM.
      GMAN, saxxie, michaelbrom and 3 others like this.

    7. #7
      Regenerative Guru Member Wallace907's Avatar
      Quote Originally Posted by GMAN View Post
      Irv what about the line about Maurie receiving cells from NED lines???

      As of september 7, the clinicaltrials.gov site has ACT injecting MA-09 hRPE cells. The only thing that changed is contact info for Wills Eye.

      As you are probably aware, it has been suggested that down the road we would be required to conduct a bridge study apart from this one in order to utilize a "true" NED line

      seems like a slight misunderstanding or a little missing info for this blog


      Perhaps Irv, or someone else would like to comment on Maurie's interpretation of her check-up relating to: I'm paraphrasing, "reduction in the darkness... suggesting healthier RPE". I interpreted her check ups with Dr. Regillo in that they were seeing MA-09 hRPE begin to pigmentate, develop and actually get darker, thereby enabling them to be seen. Unless they were talking about AF signals, Im not sure what to make of it.
      Last edited by Wallace907; 09-27-2012 at 01:11 PM.

    8. #8
      rocky301's Avatar
      Quote Originally Posted by Actc_fan View Post
      GMAN,

      My understanding is:
      - There are 4 NED lines (NED-1 through NED-4), where the hESC was derived WITHOUT EMBRYO DESTRUCTION, and the embryo was NEVER destroyed.
      - MA09 is an NED line, in that the hESC was derived WITHOUT EMBRYO DESTRUCTION, BUT, the embryo was destroyed after the process.

      So technically, creation of MA09 did not cause embryo destruction, but ACT has to be careful when stating this.

      Anyone please correct me if I am wrong. Thanks
      Actc,

      here is how ACT has made the distinction..

      NED 1-4
      Single blastomere derived hES cells without embryo destruction (the biopsied embryos were allowed to develop to blastocyst state and then frozen)

      MA09
      Single blastomere-derived hES cell lines (embryos not preserved)
      Actc_fan, LCD, dyooperya and 3 others like this.
      'TIME IS BUT THE STREAM I GO A-FISHING IN'

    9. #9
      GMAN's Avatar
      Quote Originally Posted by Wallace907 View Post
      As of september 7, the clinicaltrials.gov site has ACT injecting MA-09 hRPE cells. The only thing that changed is contact info for Wills Eye.

      As you are probably aware, it has been suggested that down the road we would be required to conduct a bridge study apart from this one.

      seems like a slight misunderstanding or a little missing info for this blog


      Perhaps Irv, or someone else would like to comment on Maurie's interpretation of her check-up relating to: I'm paraphrasing, "reduction in the darkness... suggesting healthier RPE". I interpreted her check ups with Dr. Regillo in that they were seeing MA-09 hRPE begin to pigmentate, develop and actually get darker, thereby enabling them to be seen. Unless they were talking about AF signals, Im not sure what to make of it.
      Wallace,

      Good point. The way I read the article the inference is that the cells are from NED 1-4 lines...

      GMAN
      "Those who are able to see beyond the shadows and lies of their culture will never be understood, let alone believed by the masses" Plato


    10. #10
      Regenerative Guru Member Actc_fan's Avatar
      The RPE cells in Maurie’s eye came from an hESC line derived in 2005 by Robert Lanza and colleagues at Worcester, Mass.-based Advanced Cell Technology, one of five cell lines called NED for “no embryo destroyed.”

      Her link is broken, but she is referencing this ACT paper from 2007. Summary of that paper:

      To date, the derivation of all human embryonic stem cell (hESC) lines has involved destruction of embryos. We previously demonstrated that hESCs can be generated from single blastomeres (Klimanskaya et al., 2006). In that “proof-of-principle” study, multiple cells were removed from each embryo and none of the embryos were allowed to continue development. Here we report the derivation of five hESC lines without embryo destruction, including one without hESC coculture. Single blastomeres were removed from the embryos by using a technique similar to preimplantation genetic diagnosis (PGD). The biopsied embryos were grown to the blastocyst stage and frozen. The blastomeres were cultured by using a modified approach aimed at recreating the ICM niche, which substantially improved the efficiency of the hESC derivation to rates comparable to whole embryo derivations. All five lines maintained normal karyotype and markers of pluripotency for up to more than 50 passages and differentiated into all three germ layers.


      Correct link: Cell Stem Cell - Human Embryonic Stem Cell Lines Generated without Embryo Destruction
      Avtech likes this.

    11. #11
      spangua's Avatar
      Irv what about the line about Maurie receiving cells from NED lines???
      She received cells from the MA09 line which isn't one of the '4 NED lines' technically, but isn't it 'close enough'? Being formed by the blastomere technique it is 'ned' it just so happens that the 'e' was 'd' in this instance...but it didn't need to be...
      GMAN and michaelbrom like this.

    12. #12
      GMAN's Avatar
      Quote Originally Posted by spangua View Post
      She received cells from the MA09 line which isn't one of the '4 NED lines' technically, but isn't it 'close enough'? Being formed by the blastomere technique it is 'ned' it just so happens that the 'e' was 'd' in this instance...but it didn't need to be...
      Bottom line...We know way too much here! LOL
      Last edited by GMAN; 09-27-2012 at 01:32 PM.
      "Those who are able to see beyond the shadows and lies of their culture will never be understood, let alone believed by the masses" Plato


    13. #13
      Iarons's Avatar
      Quote Originally Posted by Wallace907 View Post
      As of september 7, the clinicaltrials.gov site has ACT injecting MA-09 hRPE cells. The only thing that changed is contact info for Wills Eye.

      As you are probably aware, it has been suggested that down the road we would be required to conduct a bridge study apart from this one in order to utilize a "true" NED line



      seems like a slight misunderstanding or a little missing info for this blog


      Perhaps Irv, or someone else would like to comment on Maurie's interpretation of her check-up relating to: I'm paraphrasing, "reduction in the darkness... suggesting healthier RPE". I interpreted her check ups with Dr. Regillo in that they were seeing MA-09 hRPE begin to pigmentate, develop and actually get darker, thereby enabling them to be seen. Unless they were talking about AF signals, Im not sure what to make of it.
      I have had a brief discussion with Maurie about her last checkup -- I think the six week checkup -- and she told me that she has lots of questions to ask Dr. Regillo, who unfortunately wasn't present for that checkup. Let her tell her story, believe me, she is an excellent writer and will tell it like it is, once she knows what's going on.

      Irv

    14. #14
      Reignday's Avatar
      (A year out, the 9 patients treated so far report more vibrant color vision and improved visual acuity. The first woman treated, for example, could detect only hand-waving before the procedure, but can now read three lines on an eye chart.)


      That sounds pretty good to me.

    15. #15
      rocky301's Avatar
      Lanza description of NED lines, good read for those who haven't seen the 2008 exchange.
      Here he speaks of MED 1-5, the NED 5 lines is owned by another party as previously posted..



      Here's an edited transcript of the exchange:

      Cosmic Log: Can you explain what exactly you did, for a layman who doesn’t understand all this stuff about "blastocysts" or "ICM niches"?

      Lanza: What we did is we removed a single cell - and one of the problems unfortunately whenever you’re trying to generate embryonic stem cells is that those cells have a mind of their own. At that early stage, they like to become what’s known as trophectoderm. That’s basically the part of the embryo that’s going to go on to become the placenta when the embryo implants in the uterus.

      Before those cells can become these trophectoderm cells, they have to differentiate. And there’s a molecule known as laminin which we found ... that if you added it actually inhibits that process, and basically shifts the cell into becoming an embryonic stem cell.

      The early embryo – the blastocyst – is basically a hollow ball. The outer surface of the ball is going to become the placenta. Inside that hollow sphere is a tiny little group of cells clinging on the inside, known as the inner cell mass or the ICM. By adding this molecule we’re basically re-creating that ICM environment, so that the cell that we’ve removed becomes an embryonic stem cell.

      It really improved the efficiency dramatically. In our previous paper, the proof-of-principle study that we published in Nature a year ago, the efficiency was only 2 percent. We’re now talking anywhere from 20 to 50 percent, which is exactly comparable to what has been reported for using entire embryos.

      So basically what you’re doing is you’re trying to fool the cell chemically into thinking it’s on that inner cell wall where it’s expected to become an embryonic stem cell?

      Exactly. It’s in the right developmental environment to become an embryonic stem cell.

      What do you think this will do to the debate over embryonic stem cells? We’ve seen that the debate has already been changing over the past few months. What do you expect to happen now?

      Well, this is a working technology, so it’s here and now, and it can be used to increase the number of stem cell lines available for federal researchers immediately. We could actually send these cells out to laboratories tomorrow. And in fact, this new methodology is so efficient that we could effectively double or even triple the number of lines available within a few months.

      The research has been held up for too long. If we had more research going on with these lines, anything we learn from these real embryonic stem cell lines – say, for instance, how to generate specific cell types to treat patients – can also be applied to reprogrammed stem cells. You’ve heard of the recent breakthrough where researchers were able to use various transcription factors to create pluripotent cells. Once that technology is safe enough to use clinically, we’ll be able to apply all the knowledge that we’ve learned. So no time would be lost while we wait.

      There’s another very important point to make, and that is that we still don’t know if the new technology to reprogram cells – which we call induced pluripotent stem cells or IPS cells – is going to be able to do all the same things that normal embryo-derived stem cells can do. We don’t even know all the properties of regular embryonic stem cells. These have to be studied.

      It might be that these IPS cells can only make neurons, but not insulin-producing cells. Or even if they can, they may not be able to do it as well. Until we have these answers, we cannot afford to abandon any line of research. So I think that there’s a strong consensus in the scientific community that we really need to proceed with all these lines of research, and every advance gets us that much closer to the clinic.

      One of the concerns that was pointed out about the induced pluripotent cells was that genes had to be inserted into the cells using a virus, and that one of the genes could lead to cancer. Can you talk about how your approach differs in that respect?

      Right. So the new IPS cells, the way these cells were generated was basically by genetically modifying the cell. In several of those experiments, they used something known as c-Myc, which is very closely associated with cancer. In many of the animals where they use these cells, there was a high incidence of tumor formation. There was a new paper that allowed the researchers to eliminate c-Myc, the most offensive of those factors. However, even those cells were genetically modified – which in and of itself is associated with an increased incidence of cancer.

      The FDA would never allow us to use those cells to treat patients. So right now, a number of groups – including our own – are working on methods to create these pluripotent cells without genetically modifying the cell. There’s obviously a great deal of excitement and promise in doing that. But we don’t know how long that’s going to take. So in the meantime for one is we need to find out once we create those cells, are they the same? Can they do all the same tricks? There was one paper that suggested there was a difference in gene expression profile, which means they are different in certain respects. That has to be studied.

      These cells that we’re talking about in this particular paper are the real thing. They’re true embryonic stem cells, and they were derived from embryos. We have a considerable amount of data on these cells, and we know they can do all sorts of exciting things. Just to give you an example: We created some embryonic stem cells from a single blastomere, and actually turned them into what’s known as hemangioblasts. We found that these cells were able to cut the death rate after a heart attack in a mouse in half. Also, in animals that otherwise would have had to have their limbs amputated because of lack of blood flow, we were able to restore that blood flow completely to normal within a month.

      These very same types of cells could be used in patients. Again, these are the cells we generated from human embryonic stem cells derived from single cells. So there’s a lot of exciting potential here. And as this new IPS cell technology develops, we will have learned how to turn those cells into the cells that can help people. Right now we’re working on making biological bypasses, and making blood, so we‘re going to have figured out how to turn the pluripotent stem cells into replacement cell types that can help people. So no time is going to be lost.

      In terms of having these cells approved for use in federally funded research, what would be the procedure? Do the limits on embryonic stem cell lines apply in this case?

      None of the embryos in this study were destroyed, so for all five of these lines, the parent biopsied embryo was frozen down and remains alive. ... Clearly these embryos were not destroyed. Now there is a question of 'were the embryos harmed?' I think in that particular case, the burden of proof really lies with proving the embryos were harmed. You can’t say that these stem cell lines violate federal law without any facts, and they should not be denied federal funding because of religious opposition.

      It’s very clear that the biopsy procedure had absolutely no effect on the subsequent development of the embryos. … There are very objective scoring criteria to assess the health of the embryos. They’re the best method we have to assess whether the embryos were harmed or not.

      So I think these lines clearly should qualify for federal funding, and my understanding is that at the White House they’re waiting for this published paper before they assess what course they’re going to take.

      When it comes to developing new therapies, one of the things about the pluripotent cells is that they’re created from the skin cells of the donor, so they could be custom-made to fit the donor’s genetic profile – whereas with these cells, it's a little more complex. If these cells can be used for therapies, how would you match a person with the cell that is needed?

      Two major hurdles have plagued transplant medicine for the last several decades: One is the shortage of the cells and the tissues, and two is the problem of immune rejection. With any embryonic stem cell, the hope is that we can create unlimited numbers of these cells, and perhaps using tissue engineering, even grow up entire organs. But we still are confronted with the question of how you put those tissues back in the body. Say we have insulin-producing cells. You can’t just plunk them back in the body because your body will reject them. The great thing about the new reprogrammed cells is that you’re starting with the patient’s own skin cell so you won’t have to worry about immune rejection.

      But the other thing to consider here is that if you do a little arithmetic, you quickly realize that a lot of this technology becomes economically prohibitive. If there over 200 million people with diabetes, and several hundred million people with cardiovascular disease, you’d be talking about literally creating billions of patient-specific cell lines. Whether that’s going to be done through the reprogramming or cloning, it’s a bit impractical.

      Here’s the way that’ll probably be solved: If you look at the tissue types for the American population, you’ll find that 100 tissue types would actually provide complete matches for 50 percent of the population. You could have cells that you expand – and of course the beautiful thing about embryonic stem cells or pluripotent cells is that they’re immortal. They grow forever. Once you have a cell bank, you could use it for virtually everyone with that tissue type.

      So say you had a heart attack, and you have a narrow window of opportunity, and you want to inject certain of these cells that repair the heart. You could have those all ready, and then once you know the patient’s type you just thaw out a vial of those cells and use them.

      Would you compare this to tissue typing for a bone marrow transplant?

      Absolutely. The beautiful thing here is that we could pick people who are homozygous – that is, they have reduced complexity of their tissue type. To some extent it’s like blood. And on that front, we can now create entire tubes of blood from embryonic stem cells. If we started with a line that was O-negative, it would be a universal blood type that would match everybody. So whether we use the reprogramming cells or we found a line that was basically O-negative, once you have that line – because it grows indefinitely – you could then use that to create literally unlimited amounts of cells that would be basically a universal donor to you, me, and everyone in the country. A similar kind of thing would apply to tissues. There are certain major tissue types, and by identifying the ones that are most common, we could make a very substantial dent in matching a large percentage of the population.

      Since this still involves extracting cells from an embryo, I suppose people might ask the ethical question about what happens to those embryos that are sampled. Could you get into a situation where you’re creating life to save a life, then have an open-ended fate for that life that you’ve created and frozen?

      Actually, we’re rescuing embryos, because these embryos would be slated to be destroyed, and we’re not harming them so they’re frozen down. By generating these lines, those embryos will be protected and will not be harmed. Period.

      That’s one thing. But the other thing to consider here is if you just look at PGD [preimplantation genetic diagnosis], these are couples who will have one of the cells from an embryo sent off to the lab to be tested. And of course when it goes off to the lab, that cell is destroyed.

      What we could do is, before you send that cell off for testing, just let it divide overnight. Then send one cell off for testing, and you create a stem cell line from the rest of those cells. So you then have a genetically matched line for that child without any additional risk to the embryo. In other words, it has no impact on the clinical outcome of that procedure - but yet, there’s a benefit in that you have a line that matches the child. And that line can also be used by the whole world.

      What’s next for your research? It sounds as if you’re going to be doing some work with induced pluripotent stem cells as well as the cells described in this latest paper. Do you have a particular term for these cells?

      In our paper we’re calling them NED1, 2, 3, 4, 5 – because there’s “no embryo destruction.”

      So if they came to be called NED cells, you wouldn’t be opposed?

      No, not at all. But also, you have to realize that as we move toward the clinic with these technologies, these studies can be very expensive. It could easily cost upwards of $100 million to bring some of these technologies through clinical trials. And pharmaceutical companies are going to be very wary before they invest money in something that’s so controversial. So having a technology where they’re actually using cells where the embryo was not destroyed might actually help in that regard.

      We’re going to be speaking with the FDA in a few weeks, and we’re hoping to get permission to proceed this year to file an IND [investigational new drug application] for clinical trials, for using retinal cells to treat or prevent blindness. We also have some other projects that we're hoping in the next year or two to get into clinical trials. I know Geron, for instance, is hoping to use embryonic stem cell technology for spinal cord injuries.

      So while we’re moving ahead with developing these different cell types, we’re still confronted with the challenge of moving into the clinic. For instance, I mentioned earlier that we can generate these hemangioblasts that can keep people from losing a leg or a foot. But we don’t know how to use them without powerful immunosuppressive drugs. The hope right now is that we can use these reprogrammed cells, or therapeutic cloning, to create cells to bypass the problem of immune rejection. Either of those approaches would allow us to apply this technology and translate it into the clinic.
      Avtech, stemdynasty, GMAN and 6 others like this.
      'TIME IS BUT THE STREAM I GO A-FISHING IN'

    16. #16
      crystalmind's Avatar
      Carrot Juice (vitamin A) may help her visual cycle.
      bo-bo241 likes this.

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