By recovering well-preserved mammoth tissue, like 40,000 year old baby mammoth Lubya, scientists hope to clone the extinct beast and then birth one via an elephant.

South Korean and Russian scientists have agreed on a project right out of “Jurassic Park.” Maybe not as cool as resurrecting T. Rex, but bringing back a woolly mammoth is sure to attract paying customers. On March 13th, South Korean and Russian scientists agreed on a joint venture to do exactly that.

According to the agreement, the Russian team will collect biological samples and send them to the Korean team for processing. The Koreans hope to create healthy cell cultures from the tissue as a source for high-quality DNA. The mammoth genome was sequenced in 2008 so they have a quality check for the new samples. Once they have quality DNA, they’ll use somatic cell nuclear transfer – the same technique used to clone Dolly – to swap out the nucleus of an Indian elephant egg with a mammoth cell nucleus. The egg will then be implanted into an Indian elephant for a 22-month pregnancy.

Pretty straightforward, right? Of course not. But if all goes well we could find ourselves studying the extinct animal and learning more about it than we ever thought possible. Not to mention, if they allow it, people will come in droves to see the mythical creature with their own eyes. It would be an historical moment for genomics and recombinant DNA technologies, biology, and science as a whole, capturing the imagination of billions around the world.

The biggest challenge right now is to find tissue and isolate cells that have healthy DNA, undamaged from freezing or radiation produced from the ground. Siberia is an ideal place to search for mammoth tissue. They first emerged in the area 400,000 years ago and flourished up until very recently when they died out at the end of the last ice age about 10,000 years ago. The extent of their reign means that the Siberian tundra is stocked with mammoth remains that are relatively well preserved and thus offer hope that healthy tissue may yet be recovered. One source estimates upwards of 150 million mammoths may be frozen beneath the Siberian tundra. Rising global temperatures are said to be thawing Siberia’s permafrost and making it easier to get to the mammoths. And even though the mammoths were mostly dead by about 10,000 years ago due to a rapidly changing climate and human hunters, a small group still persisted on Wrangel Island in northeastern Siberia as recently as 4,700 years ago. Recovering tissue so recently preserved would increase the researchers’ chances for success.

Disgraced Korean scientist Hwang Woo-suk successfully cloned eight coyotes by implanting their DNA into the egg of a domestic dog

But cloning still remains a crapshoot even under ideal conditions. Of the 227 eggs that underwent somatic cell nuclear transfer in Dolly’s cloning, only 29 viable embryos were created. And that procedure involved swapping nuclei from cells of the same species. Interspecies nuclear transfer, what cloning the mammoth requires, is even trickier. As the mammoth’s closest living relative, an Indian elephant egg and female are the best choices to receive the mammoth DNA and then carry the pregnancy to term. But whether or not it will work is anybody’s guess.

It may come as a surprise to some to learn that the Korean team at the Sooam Biotech Research Foundation in Seoul is headed by none other than disgraced stem cell researcher Hwang Woo-suk. Hwang became famous overnight when, in 2005, he claimed to have created human stem cells from a cloned embryo. He was later found to have forced the women in his lab to donate their own eggs, and then later was found to have falsified much of the data anyway. But it was Hwang’s ability to perform interspecies nuclear transfer that caught the attention of Prof. Vasily Vasilyev, the First Vice-Rector of the North-Eastern Federal University in Russia. As described in a press release, Vasilyev became convinced that Hwang’s lab was the right one for the job after seeing a news report. The work has been verified by other scientists.

The Russian lab was already working with a team of Japanese researchers on the mammoth restoration project but failure to reach an official agreement with the Japanese scientists have led to the Russians shifting partners. Along with Hwang’s lab, China’s Beijing Genomics Institute is also involved in the project.

Sooam said they hope to have restored viable cells by the end of 2012. If that happens and they are then able to implant the clone egg into an elephant, it becomes a 22-month wait to see if the pregnancy works. Given the overwhelmingly bad odds for a cloned and implanted egg succeeding to birth, it seems like a really big gamble to put all your ‘eggs’ in one elephant. But no one ever accused Hwang of thinking small. There’s no telling what he’ll do next if he’s successful in raising the mammoth.

[image credits: Britannica, telecomtally.com and Wall Street Journal]
image 1: mammoth
image 2: Lubya
image 3: hwang

The man of the hour. UCLA's Steven Schwartz and his team partially restored vision to two patients by injecting stem cells into their retinas.

Macular degeneration had left Sue Freeman, 78, legally blind. She couldn’t go for a walk by herself, she couldn’t go shopping or even cook by herself. Another woman, age 51, was suffering from Stargardt’s macular dystrophy, which causes the loss of cells located in the pigmented layer of the retina called the retinal pigment epithelium. Also legally blind, she was unable read the large letters on an eye chart used to test people with compromised vision.

In July of 2010 doctors injected retinal cells derived from human embryonic stem cells into one eye of each woman in the hopes that they would regrow the cells needed to see. A couple weeks after surgery Freeman improved her visual acuity score from correctly identifying 21 letters (20/500 vision) to 28 letters (20/320). She could once again pour a glass of water without spilling it, read her own handwriting, and – to the chagrin of her husband – take notice of all the improvements that needed to be done on rental properties that they own.

The other patient, who wishes to remain anonymous, could only detect hand motions prior to surgery. Two weeks following surgery she began counting fingers. She also improved from identifying zero letters on the acuity chart to correctly recognizing five. She woke up one morning and looked at the armoire in her bedroom. “It has a lot of detailed carvings and I thought wow, I was missing those before,” she told CNN.

Both patients continued to show improvement in the treated eye four months after surgery and did not show any adverse side effects. Importantly, the eyes that did not receive stem cells did not show improvement. The patients were also given immunosuppressants to prevent their bodies from rejecting the foreign tissue.

The trial was led by Steven Schwartz, an opthalmologist and chief of the retina division at UCLA’s Jules Stein Eye Institute, and the results were published in The Lancet. Although the results are extremely promising, Dr. Schwartz is quick to temper enthusiasm over the trial. Only two patients were treated, after all. Many more will need to be successfully treated before the procedure can be accepted as a robust option. He justified publishing the study after only two patients given the amount of interest in the field. Qualifying the study further, Dr. Schwartz cautioned that the improvement in eyesight for one of the women could be a placebo effect.

Pigmented epithelial cells were grown from embryonic stem cells prior to injection.

The stem cells were treated before being injected into the patients’ eyes. Researchers at the company that had provided the stem cells, Advanced Cell Technology, had induced the cells to become retinal pigment epithelial cells. The procedure, which included the injection of about 50,000 cells, took half an hour. The team received stem cells from Advanced Cell Technology, which had gotten them from an embryo stored at a fertility clinic. The couple who’d produced the embryo decided not to use it and then donated it to the company. After stem cells were derived from the embryo it was destroyed. The hope is that in the future stem cells will be taken from embryos without the need to destroy them.

The stem cell treatment gives new hope to the blind. Macular degeneration is the leading cause of vision loss among the elderly. When the light-sensitive photoreceptors of the macula degenerate people can no longer bring objects into focus. Stargart’s muscular dystrophy, or Stargart’s disease, is a common cause of vision loss among children and young people. Right now there is no treatment for Stargart’s disease, and while drug injections, laser treatment and diet alteration can slow the progression of age-related macular degeneration, it is also considered incurable.

Others are working towards a stem cell cure for macular degeneration. In 2010 researchers successfully grew a retina in the lab from human embryonic stem cells. It was the first time a 3D tissue was produced from stem cells. Curing macular degeneration is an ideal target for stem cell treatments. The number of cells needed is low compared to, say, regrowing the neurons of a damaged spinal cord. Unlike other cells in the retina, cells of the retinal pigment epithelium don’t need to form synapses to work. Lastly, the retina’s immune environment is more tolerant, thus decreasing the need for immunosuppressants.

Pharmaceutical giant Geron Corporation used to represent one of the best chances for making stem cell treatments a reality. But recently after the company had begun human trials on their promising cell line that allowed paralyzed mice to walk again, they dropped out of the stem cell game altogether. If the UCLA trial results hold, it could entice more companies like Advanced Cell Technology to invest in stem cell research. According to a commentary on the trial, when Geron ended their trial it left ACT and Dr. Schwartz and his colleagues as the sole group treating patients with embryo-derived stem cells. That’s not good enough. Let’s hope the trial not only brings the world into focus for its patients, but also brings the potential of embryo-derived stem cells back into the focus of medicine.

[image credits: UCLA Jules Stein Eye Institute, CNN and The Lancet]
image 1: Schwartz1
image 2: Schwartz2
image 3: stem cells

Embryonic stem cells got their second FDA approval for trials. Another step in the right direction.

For only the second time in history, the US FDA has granted approval for clinical trials for a therapy derived from human embryonic stem cells. Advanced Cell Technology (ACT), a Massachusetts based bio-firm, recently announced that they had secured approval for human trials of their retinal pigment epithelial cells to treat Stargardt’s Macular Dystrophy. SMD causes blindness, generally among youths 10 to 20 years in age, and affects less than 200,000 people in the US. The recently approved trials will only involve 12 patients, and are looking primarily to establish that using the ACT cells is safe. There is hope, however, that the vision of those treated could be improved or restored. In the longer term a success for embryonic stem cells here could lead to treatments for other forms of blindness. Yet as exciting as this study may be it’s also a sad reminder of how long it has taken to get embryonic stem cells approved for human trials.

Let’s start with the best news first: ACT is on the (relatively) fast track for getting their Stargardt’s treatment to market. As we mentioned back in March, they received orphan-drug status for their retinal pigment epithelial cells (known as MA09-hRPE). That status, granted to drugs that have a relatively small and needy prospective patient base, gives them access to better funding, and accelerates the clinical trial process. The effects of this status have already been seen: ACT received NIH funding in June, and $1 million in government grants in November. They also secured patents for their embryonic stem cells in June (though this may only be partially related to their orphan status). Now, ACT is also approved to start Phase I clinical trials, and overall it looks like the FDA is treating ACT fairly well. ACT is even enjoying a small upswing in their stock (OTC:ACTC) with the recent FDA approval announcement.

While Stargardt’s is a relatively rare condition, other macular diseases are not. There are millions of people with full or partial blindness related to macular degeneration, with a potential US and EU market measured around $25 to $30 billion (according to ACT). 10% of those aged 66 to 74 are affected by these types of blindness, up to 30% in the 75 to 85 group. ACT may be bursting onto the field through an orphan-drug status, but the greater possibilities extend far beyond the (comparably) small population of those that suffer from SMD.

If ACT can prove the safety of their MA09-hRPE cells during this first phase of clinical trials it looks like they will be on the verge of great things. Yet this potential success is a little tainted in my mind by its scarcity. Besides ACT, the only embryonic stem cell derived technology to get FDA approval for human trials in the US is Geron’s treatment for spinal injury. As you may recall, the approval process for that trial was long and winding, with many delays as Geron struggled to dot all its ‘i’s and cross all its ‘t’s before being given the green light. Even ACT, which I feel like has had a relatively easy time of it, had to clear several FDA hurdles before arriving at this recent approval. The company announced its intent to pursue human trials in November of last year, and made strides in April and July demonstrating that their MA09-hRPE cells didn’t cause tumors nor spread themselves uncontrollably through the body.

In general I support regulatory approval – I certainly don’t want to take medications that haven’t been thoroughly tested. Yet I’m also frustrated, as I know many of you are as well, that promising stem cell technologies are taking so long to get to patients. Both Geron and ACT had remarkable success in their animal models. Geron got mice walking again after spinal injury and ACT had 100% success with getting rodents to grow new retinal cells after treatments (100 percent!). It’s disappointing to think that either a) the FDA doesn’t recognize the overwhelming potential of these treatments and isn’t willing to help them move along as fast as possible OR b) has been helping them, and this is as fast as it possibly can get.

The silver lining in the FDA’s rigorous review of embryonic stem cell technology is that it encourages and highlights the work that scientists at ACT (and Geron) have done to get their approval. ACT’s Chief Scientific Officer, Robert Lanza, developed a remarkable assay technique that can detect 1 stem cell among 1 million retinal pigment epithelial cells. For the SMD therapy, Lanza only wants MA09-hRPE cells that are derived from embryonic stem cells, not the stem cells themselves. As only 50,000 to 100,000 MA09-hRPE cells are used in each treatment, the 1 out of 1 million detection is more than powerful enough for these human trials. This assay technique was one of the important tools that convinced the FDA that ACT has cleared its hurdles back in April and June.

Despite my general frustration at the slow pace for embryonic stem cells, the approval for ACT’s MA09-hRPE is great news for blind patients everywhere. This is one of several exciting developments for treating blindness with stem cells. Hans Keirstead, the originator of Geron’s technology, has had success using embryonic stem cells to treat macular degeneration. Non-embryonic stem cells have a proven decade long history of treating corneal blindness. It’s still going to take years for these therapies to reach market, but they are out there. I have a lot of hope that, given enough time, humanity will conquer blindness in all its forms using stem cells and related therapies. That hope is reason enough to wade through all the necessary aggravations of government regulation. I really wish embryonic stem cell technologies would reach us more quickly, but even at a slow steady pace their arrival will be well worth the wait.

[image credit: Nissim Benvenisty via WikiCommons]
[source: ACT Press Release]

A recent court ruling could end public funding for embryonic stem cell research in the US.

Stem cell research in the United States was dealt a recent blow when a US district judge ruled that public funding for embryonic stem cell research violated federal law. Judge Royce Lamberth found that congressional statutes, which prohibited federal funding going to any research where embryos were destroyed, applied to research on embryo-derived stem cell lines. This is a surprise, as President Obama’s executive order on stem cells was thought to be a definitive opening of the field in the US. Now, stem cell scientists must scramble to determine which, if any, of their research must not use public funds in order to comply with the new ruling. Embryonic stem cells may be key to finding new treatments for painful and life threatening diseases and this decision may slow such research in the United States for years to come.

A single embryo’s stem cells can be replicated many times over, allowing each stem cell to generate a ‘line’ of cells that many different scientists can use in their research. For a time it was believed that research on pre-existing embryonic stem cell lines did not violate federal prohibitions on research that destroys embryos. As such, George W. Bush signed an executive order limiting public funding for exploration of embryonic stem cells to just 21 lines. Obama expanded that to 75 lines and opened up the possibility of new lines being created through parental consent. Both of these decisions are now in question.

The court case in question is a lawsuit filed by several parties against the federal government to stop public funding of embryonic stem cells. Those parties were led by the Alliance Defense Fund (a conservative Christian legal group) but included an adoption agency, embryos (on their behalf), and two scientists. Earlier court rulings required plaintiffs to have a clear material affect by the executive order, so all but the two scientists were stripped from the case. These two researchers, Dr. James Sherley of Boston Biomedical Research Institute and Dr. Theresa Deisher of AVM Biotechnology, argued that the expansion of public funding for embryonic stem cells would increase competition and limit the funding for their adult stem cell research. Judge Lamberth agreed that there was a clear material consequence for public funding of embryonic stem cells on the two scientists, and further decided that the embryonic stem cell lines were still research that was based on the destruction of embryos. As such, he has blocked all further public funding of embryonic stem cells.

Why is this a problem? Embryonic stem cell research may hold the promise to all sorts of amazing treatments. They could repair spinal injury, grow new retinas, or treat diseases like Parkinson’s and Alzheimer’s. Many felt that the restrictions put in place by George Bush in 2001 horribly damaged the state of US research in the field. Now, public funding could be even more limited in scope.

Yes, private funding for embryonic stem cells will still be there, but we still need public funding. Greater diversity of financing creates greater diversity in research. Public funds would also help research in to diseases whose cures would not be profitable.

You could also argue that research into adult stem cells has had proven successes and that we don’t need embryonic stem cell lines. It is unlikely, however, that adult stem cells will ever be able to replace embryonic stem cells in all forms of research. Just as we need a diversity in funding, we need a diversity in approaches. We need to explore both embryonic and adult stem cells to have the best chances of finding new treatments.

Judge Lamberth’s ruling may be detrimental to US scientific development, but it may also be a correct interpretation of federal law. Those interested in public funding for embryonic stem cell research may eventually need to champion new legislation to explicitly permit such experiments (legislatures may be working on such a bill now). Until that occurs we may be mired in executive orders, court battles, and public debates long after other nations have developed the science more fully. China, for example, has been advancing undisturbed in the field for years. Until the US makes up its mind about embryonic stem cells we are likely to continue falling further behind the global scientific community.

[image credit: Wikicommons (modified)]
[source: AP, NY Times]

Retinal tissue derviced from embryonic stem cells may one day treat macular degeneration.

Researchers at UC Irvine in California have succeeded in getting stem cells to differentiate into a retina. The work was recently published online in the Journal of Neuroscience Methods, and represents the first 3D tissue structures made out of human embryonic stem cells (ESC). The group was lead by Hans Keirstead who is also developing the first US FDA approved therapy using ESC which seeks to treat spinal injuries. While still in the very early stages of development, the ESC-derived retinal tissue may help treat millions of people in the world that suffer from loss of vision due to macular degeneration and retinitis pigmentosa. This is yet another example of how stem cell derived therapies could revolutionize medicine.

There are roughly 10 million Americans with macular degeneration (and many more around the world), most of whom will suffer partial or complete loss of vision. There are several upcoming approaches to treating this type of blindness. A mechanical solution in the form of a telescope implanted into the eye has already had proven success and is awaiting FDA approval. Electrical artificial retinas connected directly to the body’s nerves are under development and have shown steady improvement in the last few years. Stem cells, however, offer the potential for either healing retinal damage in situ or replacing damaged tissue with newly grown retinal cells. UC Irvine’s work opens the door for both of these solutions by exploring what it takes to get ESCs to differentiate into the appropriate retinal cells.

That differentiation isn’t simple. The retina has a complex set of cell types that allow it to function. In order to foster the correct growth, the UC Irvine team placed the embryonic stem cells onto a patch of retinal pigment epithelium. The ESC were then bathed in a special gradient of solutions to promote growth into adult cells. The UC Irvine group found evidence of ganglion cells, photoreceptors, and more.

I really want to emphasize that this is very preliminary work, essentially a proof of concept. While Keirstead and others have a remarkable history of success with ESC, this work with retinal tissue is just the first step towards developing a meaningful therapy. The next stage will be testing in animal models (plans for that are already underway), and only after that is complete would we see human trials begin. We’re talking many years here.

Still, the retinal-ESC differentiation is a great sign of the advances in research that are likely to arise with the US’s renewed pursuit of embryonic stem cell technology. This work is some of the first to come out of UC Irvine’s new Sue and Bill Gross Stem Cell Research Center which opened last month. That center is home to a remarkable set of scientists including Hans Keirstead and the other authors on this paper: Gabriel Nistor, Magdalene J. Seiler, Fengrong Yana, and David Ferguson. Hopefully we’ll see much more out of the UC Irvine group in the years ahead as they enjoy continued funding by local, state, federal, and private institutions.

[image credit: National Institute of Health]
[source: UC Irvine News, Nistor et al JNM 2010]

Hans Keirstead is the scientists behind the first embryonic stem cell clinical trial in the US. He explains the hurdles that research faces to becoming a viable medical therapy.

Hans Keirstead used embryonic stem cells to help paralyzed rats walk again. His research is the basis for the first FDA approved clinical trial for the use of embryonic stem cells (ESC) - currently underway by Geron and aimed at treating spinal cord injuries. After years of controversy in the first part of the decade, ESC trials have finally started on the path that may let them deliver on the vast promises of stem cell enabled medicine. Yet we have already seen how autologous stem cell therapies (those which use a patient’s own cells) are becoming available in the U.S and all over the world. Why the hold up on ESC treatments? Autologous therapies are part of the medical practice of individual doctors, given to their individual patients. Geron’s clinical trials hope to usher in a new wave of globally used drugs and procedures. The rigorous science needed to obtain FDA approval for such widespread treatments is not easily achieved, but many still lament the slow process. To all of us wondering why ESCs are not yet available in every hospital across the world, Hans Keirstead has an explanation. He doesn’t make an impassioned plea, or take a rhetorically defensive stance. In just 5 minutes Keirstead walks us through the fundamental hurdles that scientists face as they try to bring ESC therapies to fruition. Everyone who wants an intellectual and scientific explanation of stem cell research should watch the video below.

Besides genetics, the application of stem cells is the defining medical technology of the early 21st century. With it we may be able to revolutionize organ transplants and develop treatments for conditions ranging from blindness to AIDS. Autologous treatments hold remarkable promise, but so too do ESC derived drugs which may use the cells of one individual to treat thousands. With so many hopes pinned to stem cell therapies it’s no wonder that many are frustrated at their unavailability and seek to obtain them outside the US. We can lament the slow process of FDA approval, and the seemingly needless politicking and bureaucracy that surrounds it. However, as we seek the benefits of advanced technologies it’s important to remember the very real and necessary scientific steps that they must proceed through before we can all safely enjoy them. Many thanks to Dr. Keirstead and CIRM for the brief but precise video explaining just that.

[screen capture and video credit: CIRM]
[source: University California Irvine, CIRM]

ACT gained FDA orphan drug status for its embryonic stem cell derived product MA09-hRPE.

Massachusetts based biotech company Advanced Cell Technology recently announced that the FDA has granted orphan drug status to MA09-hRPE – an embryonic stem cell derived treatment for a specific form of blindness (Stargardt’s Macular Dystrophy). Orphan drug status is targeted to those therapies which are designed to treat fewer than 200,000 Americans and gives ACT access to tax credits, grants for clinical trials, and a seven year exclusivity to market MA09-hRPE. This is the first such FDA approval for an embryonic stem cell derived therapy and ACT plans on using the orphan drug status to accelerate clinical testing. While Advanced Cell Technology has something of a checkered past, this recent FDA status could signal not only an approaching success for the MA09-hRPE treatment, but also a promising advancement in the company’s goal to pioneer new forms of regenerative medicine.

Up to now the only real US embryonic stem cell derived treatment fit to discuss was Geron’s therapy for spinal cord injury which has been stalled off and on in clinical trials. As such, ACT is joining a very exclusive club, albeit for a disease that has a fairly narrow base of patients. US research into embryonic stem cell technologies was stunted after the Bush administration restricted federal funding. Now, Geron and ACT may represent a new page in that research – a growing trend of the US recovering for lost time and developing new stem cell technology. As we’ve seen with the increase in US medical tourism, Americans (and many others around the world) are anxious to get their hands on stem cell treatments.

ACT’s development of MA09-hRPE could help restore the vision of thousands. Macular dystrophy affects millions in the US and around the world. Stargardt’s (SMD) affects many fewer (less than 50k in the US), but can still lead to permanent blindness by destroying the retinal pigment epithelium (RPE). ACT has shown success in rodent tests by introducing the embryonic stem cell derived RPE cells into the eye. According to the ACT press release, this resulted in 100% improvement with no side effects, and with the RPE cells lasting for more than 220 days. Those are remarkable and very promising results.

However, ACT’s scientific claims are still tainted by some mistakes made earlier in the century. Under former CEO Michael West, ACT announced a series of results that may have overstated their accomplishments. Among these was the cloning of a human embryo and the cloning of an endangered species (the gaur). Critiques pointed out that the embryo cells replicated slower than normal and the gaur died before adulthood. There were also serious financial troubles in 2008 when the company seemed on the brink of bankruptcy. Now, they have a new CEO, William Caldwell, and seem to have plenty of cash flow, though their stock prices are still low (OTC: ACTC).

Thankfully, ACT’s reputation is bolstered by its Chief Scientific Officer Robert Lanza. Lanza is something of a rock star scientist. He’s been called the real life version of Will Hunting (from the movie Good Will Hunting) and made his entry into biological sciences by altering the genes of chickens in his basement. He’s a Fullbright scholar, an associate professor at Wake Forest, and has written the book on tissue engineering (I mean that literally: Principles of Tissue Engineering). We’ve covered his work on creating blood from embryonic stem cells, which he discusses in this brief clip from his interview with Barbara Walters.

I am cautious in my optimism about ACT’s MA09-hRPE, but then again I am cautious about all medical treatments in clinical trials, especially stem cell therapies as they are so often hyped. Still, the fact that ACT has received FDA orphan drug status for its MA09-hRPE is a great sign for the company, and for US embryonic stem cell research. One hopes that the FDA approval process will continue to allow more embryonic stem cell (and non-embryonic stem cell) research to progress swiftly towards becoming publicly available. For those suffering from Stargardt’s Macular Dystrophy, ACT’s work is a promising treatment to possibly slow down or even reverse their condition. Best of luck to ACT and stem cell researchers everywhere.

[image credit: Advanced Cell Technology]
[video credit: ABC News]

By color-coding stem cells, reserachers isolated those that would form different parts of the heart.

It’s Alive! Researchers at Harvard University and Massachusetts General Hospital have succeeded in taking embryonic stem cells from mice and growing cardiovascular tissue. The research team, led by Dr. Kenneth Chien, believes that a similar process may one day serve to repair cardiac damage in humans. The work was recently published in the journal Science. You can see the mouse heart cells beating at different speeds in the video from Boston.com after the break.

Cardiac injury is some of the most difficult damage to heal in the body. When the heart undergoes massive damage from a coronary, you have few options – replace broken parts, add a pacemaker, or get a whole new heart. The work done by Chien and his team focuses on creating a new way to repair tissue damage. Instead of adding in mechanical parts, or finding a donor organ, stem cells may be used to replace and heal the damaged cardiac tissue. Eventually, those patients that develop a myocardial injury could have pluripotent stem cells harvested from their skin, marrow, or fat which would then be introduced into the heart via injection. No open heart surgery, no pacemakers, just stem cells and a needle.

While the pulsing tissue in the video is cool looking, readers may recall that we’ve seen far more advanced stem cell creations on Singularity Hub. Researchers at the University of Minnesota have created entire mouse and pig hearts that beat. Those videos are much more impressive. What then, makes the Harvard/MGH research so noteworthy?

Unlike the Minnesota work, the Harvard project isn’t aimed at creating entirely new organs. Instead, Chien and his colleagues have developed a manner to differentiate between different pluripotent stem cells. They introduced a color coding system via genetic engineering so that the stem cells could be selected based on which part of the heart they will become. Using this technique, the appropriate mouse stem cells could be cultivated to replace/heal just one portion of the damaged organ. It’s that identification and isolation of stem cell types that is so unique for this work.

Using their technique, the team is ready to start the next step: developing a 3D collection of mouse cardiac tissue. After that, the team could start performing heart repair on living mice. If successful, it will likely take many years of research and clinical trials before such a stem cell therapy would become a publicly available treatment in humans. Still, these current results show that Chien and his team are able to find the right stem cells for the job.

Though watching a newly formed heart beat is more impressive than watching the same motion in a tiny strip of tissue, we should remember that we really need both. Some damage from heart attacks will be able to be repaired. Other damage or chronic forms of heart disease will require a full organ transplant. By pursuing both options, researchers in Massachusetts and Minnesota will eventually provide the best possible health care. And it’s needed. According to the CDC, heart disease is the leading cause of death in the US, about 27% of total lives lost. Similar rates are seen throughout the developed world, primarily because of poor lifestyle choices. C’mon little mouse heart tissue, keep beating! We’re all going to want your help real soon.

[Video Credit: Boston.com and Kenneth Chien et al]

Artificially created blood? That's for real. Vampires? Yeah, not so much.

Ask any vampire and she’ll tell you, when it comes to blood there’s nothing like the real thing. But as everyone who donates knows, hospitals and blood banks always seem to have dangerously low supplies. So scientists have gotten around to finding ways to make new blood, or something like blood, that doesn’t have to come from humans but that can still supply human demand. The new blood comes in two flavors: blood substitutes (without red blood cells) and synthetically produced blood (derived from stem cells). While it looked like blood substitutes could be the dominant force in the market, that is quickly changing. Why? Well, it turns out that synthetic blood is less likely to kill you.

A recent study published in the Journal of the American Medical Association (JAMA) and led by Dr. Charles Natanson has revealed that five major brands of blood substitute were increasing the likelihood of heart attacks and death. This has devastated interest in blood substitutes and bankrupted several companies that hoped to produce it. Synthetic blood is now the future vampire’s soup du jour.

No matter which substance ultimately triumphs (and both may still succeed), natural blood donations may eventually become things of the past. Why worry about diseases, spoiling, and matching blood types when an endless supply of near perfect blood could be available. Hemophiliacs to wounded soldiers, everyone could end up enjoying a new kind of blood.

Fake Blood, Real Problems

Your blood’s major duty is to carry nutrients, including oxygen. Hemoglobin, the chemical that absorbs and transfers O2 can be removed from your red blood cells. Outside of red blood cells, and mixed with oxygen rich materials and proprietary chemicals, hemoglobin has a long shelf life (12 months compared to normal blood’s 6 weeks) can get oxygen to your cells fast, has little chance of transmitting disease, and avoids any need to match blood types. This miraculous fluid is known as a hemoglobin based blood substitute (HBBS). Back in the early 80s when 1 in 100 blood donations might contain a contaminant, HBBS seemed like a great idea. In the last five to ten years, that great idea started to seem like a real possibility.

Unfortunately, hemoglobin outside of red blood cells has a problem. It likes to scavenge nitric oxide (NO) and that’s a bad thing. It can constrict your blood vessels, cause low blood flow, damage your pancreas, and cause heart attacks and death. Charles Natanson at the National Institute for Health and his teammates studied every bit of scientific literature they could get their hands on published between 1980 and 2008. Looking at just the cases where adults were given HBBS they found 16 clinical trials that used 5 brands of HBBS and discussed 3711 patients. As Natanson published in JAMA, HBBS led to a significant statistical increase in the risk of heart attack and death. These results were not limited to a particular brand or clinical trial.

Yeah, sometimes an entire class of kids flunks out. It happens. The five brands in question were: hemolink (created by Hemosol Bio Pharma), hemopure (created by Biopure Corp.), hemospan (Sangart, Inc), Optro (Baxter Worldwide), and Polyheme (Northfield Labs). Of those five, Northfield Labs and Biopure Corp both filed for bankruptcy, and Hemosol’s website is suspiciously down most of the time.

Of course, every class has a teacher’s pet. HemoBioTech, who wasn’t included in the JAMA study, has supposedly lowered the toxicity of its brand of HBBS. Making molecules larger and more stable apparently alleviates some of the NO scavenging problems. The future of blood substitutes rest on the shoulders of HemoBioTech and other companies looking to create the next (and better generation) of HBBS.

I could do an entire story just on the aftermath of the Natanson JAMA article. Man, stuff hit the fan. Just some highlights: the FDA was very unwilling to release confidential/secret documents from HBBS manufacturers when Natanson was doing his research. This lead to some huge debates about whether the FDA should protect the privacy of companies when the public health is on the line. The FDA finally approached all five HBBS manufacturers and told them to go back to the drawing board. As we said, some companies folded under the pressure. The debate on what information should be available to peer scientists and reviewers is still raging on.

Need blood? Ask the frozen embryo for some help. Or maybe your baby’s umbilical cord.

I wouldn’t call it a fad, but it seems like every major medical problem these days is about to be cured by stem cells. In the case of blood, major research is underway in the UK and US to utilize stem cells to generate blood without a donor. That is, stem cells can be used to generate synthetic blood in a lab that is, for all intents and purposes, identical to normal blood from a human.

The Wellcome Trust, along with the blood transfusion services of England, Wales, Scotland and Ireland are donating millions of pounds and expertise to research how embryonic stem cells can be converted into an endless blood supply. As ESCs can be coaxed to replicate almost infinitely, and stimulated to become red blood cells, an entire nation’s blood supply might be able to be derived from just one discarded frozen in vitro fertilized embryo. An US company, Advanced Cell Technology is working on a similar project in the US, though it struggles with some of the legacy from the Bush administration’s ban on ESC research.

Obviously ESCs bring with them ethical debates and considerations. Even if a single embryo could supply the nation’s blood, that’s a risky approach (never put all your red blood cells in one blood basket). Undoubtedly the use of ESCs to make synthetic blood will require the destruction of dozens of frozen embryos. For some, one would be too many. I’m sure the UK and US projects will face heated debate. Nothing really new about that, though.

Arteriocyte, Inc might sidestep the issue by creating synthetic blood not from ESCs, but from the blood taken from newly cut umbilical cords. Cord blood is an interesting topic unto itself and we’ll be having a post on that real soon. Other types of adult stem cells, such as induced pluripotent stem cells (iPSCs) can also be converted.  When it comes to new blood, umbilical cord stem cells and iPSCs don’t have the oomph of ESCs, but they might still get the job done.

With the health risk problems facing HBBS, synthetic blood seems like the clear winner in the race to be the new blood. However, we should keep in mind that while 1 in 100 blood donations had problems in the 80s, the new statistic is much closer to 1 in 10 million. Huge improvements in screening tests have made donated blood extremely safe. So the only real advantage new blood has over traditional blood donations is availability, compatibility, and scalability. ESC derived blood will certainly be O-type and compatible, but it hasn’t been shown to be scalable to large quantities. HBBS has its own scaling issues, but it is universally compatible, and can be stored for a long time.

Several years down the line, we may also want our new blood to be better than the old stuff. While in your body, the new blood could supply  more oxygen stored in each red blood cell (or with each hemoglobin), have better transfer rates, and maybe provide increased resistance to infections. The ultimate goal would be respirocytes, a version of blood with nanotech containers holding stored oxygen so that you would have enhanced endurance. That’s years or decades away from happening, but the new blood we discuss today might be precursors to that technology.

In the end, the competition between HBBS and stem cell generated blood is actually far from finished. Which is good news for all us blood-thirsty people out there. I always like it when technologies compete, it gives us better results faster. In the meantime I’m looking up how I can donate blood. It’s old school, but it still saves lives. And it makes vampires happy. Double win.

[photo credits: Showtime Ent.]

First, lets set the record straight.  Chinese scientists did not create an entire functioning mouse simply by reprogramming some mouse skin cells.  What they did do was reprogram mouse skin cells back into their more versatile, pluripotent embryonic state and inject them into an already healthy early stage mouse embryo.  The embryo, now partly its original self, and partly augmented with the foreign cells that were injected, was able to continue to grow normally into a fully mature, reproductively viable mouse.  What is the point, and why do we care?

The first point of interest here is that the study joins a  growing mountain of studies that show that mouse and even human skin cells can be reprogrammed into pretty much anything.  In this particular study, skin cells from a mouse were essentially reprogrammed into embryonic stem cells.  These reprogrammed skin cells were injected into an early stage embryo and then multiplied and mutated into all of the many different types of cells and tissues required to make a mature mouse.  In the coming decades this type of research could unlock the ability to take your own skin cells and create any cell, tissue, or organ you need for your body without any fear of rejection by your immune system.  Immortality anyone?

If you think for a moment about the mouse that was created in this study, you will quickly recognize what I believe is perhaps the most interesting and thought provoking aspect of the research of all: the mice that were created had some cells that had dna from the original embryo and some cells that had dna from the injected pluripotent cells.  This is a highly unusual situation – a true perversion of nature.  In normal individuals, mouse or human, every single cell throughout the individual’s body has the same dna that is unique to that particular individual.  The dna in your skin cells, liver cells, neural cells, and every other cell in your body is essentially identical, having all originally derived from a single fertilized egg.  Not so with the mice created in the Chinese study.  The mature mouse in this case had some cells with dna from the fertilized egg, and other cells with a completely different set of dna that derived from the cells injected into the embryo.

The resulting mature mouse, containing two completely different sets of dna residing in different cells randomly throughout its body is extremely interesting.  It is surprising to some degree that the embryos were even able to mature in such a scenario, but mature they did.  It poses new possibilities, new horrors, and new questions.  What sort of perverse side effects could result from an organism with multiple sets of dna residing in its body.  Will all of these different sets of dna play nice with each other, or will there be nasty side effects?  On the flip side, could there be benefits?  Imagine an organism with one dna profile in its liver cells, specialized specifically to create super awesome liver cells.  Meanwhile, other organs could have their own dna profiles specially suited to their task.  There is much to ponder here.

Also of note here is the origin of the study – China – instead of one of the usual developed world nations.  It is exciting to see China and other countries rising economically and academically in recent years so that they may contribute to a future for man that knows no borders.  We need all of the help we can get to solve man’s greatest problems in health and beyond.  For too long a very few nations representing a small percentage of the world’s brainpower and potential have carried the mantle of research.  Now the great minds of China and the rest of the world are joining that cause and this is great news.

So where do we go from here?  The major thrust moving forward will be to continue the work of this study and thousands of others that are trying to figure out just how far we can take these induced pluripotent cells.  The promise is that we can take anyone’s skins cells and reprogram them to become new cells, tissues, and organs that can be used to heal and repair our bodies.  We need to do this and we will.  Lets just hope they figure it out within our lifetimes.  Furthermore, a new paradigm of biology has been presented by this research – an organism with more than one set of dna coursing through its body.  It will be interesting to see this paradigm develop over time.

C'mon girl, help me get a stem cell treatment!

What are these treatments promising? According to anecdotes, the results are amazing. Old dogs with bad hips frolic like puppies. Race horses with injuries come back to become world class winners. One such racehorse, Be A Bono, won 16 out of 24 starts, earned more than 1.3 million in prize money, and was the 2004 World Champion Quarterhorse. All after a stem cell treatment. The success stories with dogs are equally remarkable, if a little tinted by emotion; check out the video from Vet-Stem after the break.

Most animals that have been treated with stem cells suffer from joint ailments. Damage to cartilage, tendons, ligaments, or arthritic inflammation top the list. Stem cells are seen as a way to provide almost magical regenerative healing to combat these ailments. The process is actually pretty simple. Rather than embryonic stem cells, adult stem cells are used. These adult stem cells are harvested in a veterinary office from fat cells in the animal, and then sent to a lab. Processing separates out the stem cells from other cells, and a concentrated dose is sent back to the vet (The turn around time for processing is only a day). The adult cells are then injected into the animal in the area that needs regeneration.

Regulation does not necessarily stop research, but it tends to slow it down as it navigates bureaucracy. That’s where the helpful word “autologous” comes into play. An autologous transplant is one where the donor and the patient are the same organism: like a fat transplant from your buttocks to your lips, or like the horse and dog treatments we just discussed. Autologous transplants of stem cells in animals are not regulated by the federal government and this has led two competing companies, Vet-Stem and Vet-Cell, to specialize in providing veterinarians with stem cells for their equine and canine patients.

From the Horse’s Mouth

The anecdotal results may be hyperbolic, but the clinical numbers are no less noteworthy. In clinical trials by Vet-Stem, 66 horses were treated and 77% saw marked improvement and a return to racing. Vet-Cell’s trials used 82 horses and had a success rate of 78%. Critics are quick to point out that company run experiments are a far cry from double-blind clinical trials, but both companies have treated thousands of horses and are making huge strides into the small animal market (read here: dogs).

Equine results from the Vet-Cell website.

Of the 1500 veterinarians that Vet-Stem has trained to perform autologous stem cell transplants, more than 60% specialize in small animals. That means that most of the transplants have moved from equine athletes to canine companions. With a price tag less than $3000, the stem cell treatment is actually cheaper than many hip replacements surgeries for larger dogs (as much as $10k or so). As Vet-Stem and Vet-Cell promote the efficacy of the treatment, you can expect more and more dog owners to be stepping up and demanding it for their pets. Considering the attachment between pet and owner, it’s an easy sell.

The harder sell would be to convince academia to validate the clinical findings…or so you would think. But of the four U.S universities that have veterinary stem cell projects (UC Davis, Colorado State University, U Penn, and Cornell) all have expressed cautious optimism about the success of treatments on their test subjects. CSU treated 15 race horses and saw 10 return to active competition. Not quite the 78% success rate of Vet-Cell, but still impressive. The UC Davis Regenerative Medical Laboratory is expanding to accommodate more work in the area as well.

Which isn’t to say that anybody really knows how these autologous stem cell treatments actually work. There’s a large debate between scientists whether the stem cells are actively reassigning to become mature cells of different types (bone, ligament, etc) or whether their presence promotes healing by releasing cytokines (cell to cell communication chemicals). There’s even argument over which kind of adult stem cells to use. Vet-stem favors fat cells, while most of the universities favor bone marrow cells. Fat cells are more plentiful, but perhaps less potent. Marrow cells are more potent, but have to be cultured to provide enough for treatment. Definitive answers to these debates may take years to resolve, but that hasn’t stopped animals from being treated today.

It Really Gets My Goat

The first equine autologous procedure was performed around 1995 by Douglas Herthel DVM. He was reporting regular success by 2001. Be A Bono was treated and then became a champion in 2004. It’s now half way through 2009 and Vet-Stem and Vet-Cell are going strong. They train new veterinarians every year in the procedure and they can process dozens of sample each week. This is amazing technology, which still needs more testing, but right now is one of the more miraculous cures in veterinary medicine. Similar treatments for humans don’t exist yet. So your horse or dog can benefit, but you can’t.

There’s a lot of really great reasons why this is so. Human test subjects are not animal test subjects, and clinical trials for humans have to be more rigorous and take longer. Collecting and isolating adult stem cells in humans still needs more time to be perfected. This technology is largely focused on joint ailments, which are important for humans, but not life threatening as they are for horses and dogs.

There are also a lot of stupid reasons why autologous transplants are years behind in humans, mainly bureaucracy, debate, and fear. I can’t help but look at these veterinary treatments and feel disappointed and angry that similar treatments are not available for humans in the U.S. Perhaps that’s an ignorant reaction. Look at the progress being made in the animal trial stages for organ replacement, or even the madcap use of stem cells in other countries, however, and you get the feeling that caution in the United States is stifling our development.

Still, progress is being made. The British parent company of Vet-Cell is starting Med-Cell, and hopes to bring the autologous treatment to humans suffering from problems in the achilles tendon. The National Institute of Health is funding programs that will focus on bone marrow stem cell treatments for arthritis, and musculoskeletal and skin diseases. ABC news Nightline recently did a report on the veterinary treatments that raised awareness and sparked a lively debate on stem cells once again.

Most of the controversy on stem cells seemed to stem from the use of embryonic cells. George W. Bush banned such research in 2001, Barack Obama opened the research again in 2009 both with great hullabaloo. The use of embryonic stem cells, however, is just one option. Adult stem cells are also viable for treating illnesses as autologous veterinarian joint treatments show. As the success of stem cell treatments continue, I hope that the bureaucracy works to adapt (or minimize) regulation so that it can promote research while still maintaining the safety of the public. That public is clamoring for better, faster, and cheaper treatments that stem cells could provide. Throw us a frikin’ bone here.

red blood cells

Currently the world’s blood supply is obtained from human donors in a system that is short on supply and fraught with complications related to sterilization, contamination, disease, storage life (typically less than 42 days), and collection logistics.

The Long:
First off, one can’t help but be a little skeptical here because of the financial condition of Advanced Cell Technology, which reportedly is on the brink of bankruptcy. Their website appears not to have been updated in several months, perhaps symbolizing the malaise that is happening over there.

Let us hope that this research truly is legit, however, because it would be a fantastic breakthrough for mankind. Other researchers have been able to derive red blood cells in the past from sources such as cord blood and bone marrow, but these sources are still donor limited. They are also rarely of type O(-) which is the universal blood type that virtually every person can accept. Embryonic stem cells can be multiplied infinitely, allowing for the generation of unlimited blood supply and theoretically can be developed into type O(-).

This breakthrough is still nowhere near to producing a clinical trial and has many technical hurdles to overcome, so don’t expect anything to come of it for many years. Still, it is exciting to see a breakthrough that might be taking us that much closer to an improved blood supply. Now, if someone could just make us a respirocyte then we would really be in business!

The research paper was published in the journal Blood.