Tag Archives: stem cell

Defeating HIV: second patient in history goes into sustained remission after stem cell transplant

After the famous ‘Berlin patient’ ten years ago, a second person has now experienced remission from HIV. After a stem cell transplant (intended to treat cancer), the patient appeared to be HIV-free and has remained so for 18 months so far. The patient, whose case is presented in the journal Nature, is a man in the UK who has chosen to remain anonymous.

It’s a case of the “happy side effect” in a very unfortunate situation: after the patient was diagnosed with HIV in 2002, he was also diagnosed with advanced Hodgkin’s lymphoma in 2012. To treat the cancer, researchers at the University of Cambridge and University of Oxford carried out a stem cell transplant. However, just like in the case of the ‘Berlin patient’, the stem cell transplant came from donors with a protein mutation known as CCR5. HIV uses the protein to enter immune cells, but the mutated version renders the virus unable to attach itself to the cell walls — essentially protecting the body from the HIV.

The transplant proceeded without major complications. The patient also underwent chemotherapy, which can be somewhat effective against HIV as it kills cells that are dividing, but the key aspect here is the CCR5 receptor, which prevents HIV from rebounding after the treatment.

After 18 months, the patient appeared to be virus-free, although researchers are still skeptical of using the word ‘cured’.

It’s still only a sample size of two, but it’s the first time the ‘Berlin patient’ results have been replicated.

“By achieving remission in a second patient using a similar approach, we have shown that the Berlin Patient was not an anomaly, and that it really was the treatment approaches that eliminated HIV in these two people,” said the study’s lead author, Professor Ravindra Gupta (UCL, UCLH and University of Cambridge).

The study is even more exciting as reactions from the research community were very positive.

“This is good quality research and the authors used the best available technology to demonstrate with the highest degree of certainty currently possible that the patient is free of the virus,” says Prof. Áine McKnight, Professor of Viral Pathology at Queen Mary University of London.

“This is a highly significant study. After a ten year gap it provides important confirmation that the ‘Berlin patient’ was not simply an anomaly.”

Unfortunately, this is not really a scalable treatment option for HIV. Large-scale stem cell transplants would be impractical and risky. However, it represents something that might be incorporated into future treatments. Some teams are examining whether gene-therapy techniques to induce mutations on the immune system could be an option. However, there are also considerable risks, particularly when it comes to affecting other genes in detrimental ways.

Furthermore, the patient had a rare variant of HIV. There are two main variants: one uses the CCR5 co-receptor and the other uses the CXCR4 co-receptor. The vast majority of cases are in the first category, whereas this British patient fell in the second category.

“The authors clearly point out that the technique will not necessarily be effective for all HIV infected individuals, specifically those infected with CXCR4 viruses. However, the principal of targeting co-receptors may be of universal benefit,” adds McKnight.

There are currently around 37 million people living with HIV worldwide, and the only available treatment is to suppress virus — but even this treatment is only reaching 59% of the patients, and drug-resistant HIV is a growing concern. Almost one million people die annually from HIV-related causes.

“At the moment the only way to treat HIV is with medications that suppress the virus, which people need to take for their entire lives, posing a particular challenge in developing countries,” said Professor Gupta.

The study ‘HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation’ was published in Nature.

Credit: M.C. Thier/DKFZ.

Scientists turn blood cells into neural stem cells, opening door for new regenerative therapies

Researchers in Germany have reprogrammed human blood cells, as well as other types of cells, into a previously unknown type of neural stem cell. These cells are similar to those that develop during the early embryonic stage of the central nervous system. In the future, such cells — which can be multiplied indefinitely — might become a fundamental building block for novel regenerative therapies.

Credit: M.C. Thier/DKFZ.

Researchers in Germany found a novel pathway to generate stem cells from blood cells for the first time. Credit: M.C. Thier/DKFZ.

Stem cells are cells with the potential to develop into many different types of cells, while also serving as a major and robust repair system for the body. Using a very loose analogy, one might say stem cells are a bit like Transformers –in that they can transform into all sort of different things, have both positive or negative effects, and are pretty darn cool.

The problem with stem cells used to be that scientists could only harvest them from embryos, which obviously has many downsides, both ethical and practical. But that all changed in 2006 when Japanese researcher Shinya Yamanaka found a way to reverse the course of development of adult cells, thereby turning them back into stem cells — so-called induced pluripotent stem cells (iPS). By using four genetic factors, Yamanaka demonstrated how virtually any type of cell, be them skin cells or pancreas cells, could be coaxed into transforming into embryonic-like stem cells, which can then be transformed into any type of cell. For this monumental discovery, Yamanaka was awarded the 2012 Nobel Prize for Medicine.

Andreas Trumpp, a researcher at the German Cancer Research Center (DKFZ) and Director of HI-STEM in Heidelberg, used a similar technique to Yamanaka. Trumpp and colleagues used four genetic factors as well, but these were different, which led to the reprogramming of cells to an early stage of development of the nervous system.

Previously, scientists had been able to a degree to reprogram mature cells into nerve cells or neural precursor cells. However, the resulting nerve cells could not be multiplied and only existed as a heterogeneous mixture of different cell types, making them inappropriate for therapeutic purposes. 

In contrast, the reprogrammed cells using the technique developed at Heidelberg produces homogeneous cells, which resemble a stage of neural stem cells occurring during the embryonic development of the nervous system, and can be used medically. The researchers call them “induced Neural Plate Border Stem Cells” (iNBSCs), which can develop in two important directions: cells of the nervous system or cells of the neural crest (i.e. peripheral sensitive nerve cells, skull cartilage).

Trumpp and colleagues successfully reprogrammed tissue cells of the skin or pancreas, but also blood cells. This means that in the future, a patient who suffers from a disease of the nervous system could be treated simply by drawing blood, and then having nerve cells made from those blood cells plugged back into the body.

“This was a major breakthrough for stem cell research,” Trumpp said in a statement. “This applies in particular to for research in Germany, where the generation of human embryonic stem cells is not permitted. Stem cells have enormous potential both for basic research and for the development of regenerative therapies that aim to restore diseased tissue in patients. However, reprogramming is also associated with problems: For example, pluripotent cells can form germ line tumors, so-called teratomas.”

The authors claim that iNBSCs could be incorporated into personalized medicine. Since the donor cells come from the patient, the immune system will recognize the differentiated iNBSCs as its own, thereby avoiding any rejection issues. Furthermore, iNBSCs can be modified using CRISPR/Cas9 — the gene editing tool that scissors bits of DNA and then glues the strands back together.

“They are therefore of interesting both for basic research and the search for new active substances and for the development of regenerative therapies, for example in patients with diseases of the nervous system. However until we can use them in patients, a lot of research work will still be necessary,” Trumpp concluded.

The findings were reported in the journal Cell Stem Cell.

Credit: Pixabay.

Never skip leg day: study finds hind leg inactivity causes neurological problems in mice

A new study performed by Italian researchers is rewriting medical textbooks. The findings suggest that inactivity in the hind legs of mice alters the rodents’ nervous system, leading to poor health outcomes that may partially explain why some patients with neuron disease, multiple sclerosis, spinal muscular atrophy and other neurological diseases often rapidly decline in cognitive functions when their movement becomes limited.

Credit: Pixabay.

Credit: Pixabay.

For the study, researchers at the Università degli Studi di Milano, Italy, immobilized the hind legs of mice, but not their front legs, for a period of 28 days. Otherwise, the mice were left to themselves, continuing to eat and groom as they normally would. The mice did not exhibit any signs of stress.

At the end of the trial, the team found that limiting physical activity decreased the number of neural stem cells in the subventricular region of the brain by 70 percent compared to the control group. What’s more, both neurons and oligodendrocytes — specialized cells that support and insulate nerve cells — didn’t fully mature when exercise was severely reduced.

“Our study supports the notion that people who are unable to do load-bearing exercises — such as patients who are bedridden, or even astronauts on extended travel — not only lose muscle mass, but their body chemistry is altered at the cellular level and even their nervous system is adversely impacted,” said Dr. Raffaella Adami from the Università degli Studi di Milano, Italy, in a statement.

“It is no accident that we are meant to be active: to walk, run, crouch to sit, and use our leg muscles to lift things,” Adami added. “Neurological health is not a one-way street with the brain telling the muscles ‘lift,’ ‘walk,’ and so on.”

It’s the brain that commands muscles how and when to contract in order to elicit movement. However, the findings show that muscles also send their own signals to the brain, with consequences for neural health.

When the researchers investigated the connection more closely, they found out that lack of physical activity lowers the amount of oxygen in the body, leading to an anaerobic environment and altered metabolism. Furthermore, reduced exercise impacts two genes. One of these, CDK5Rap1, is known to be critical to the health of mitochondria –– rod-shaped organelles that can be considered the power generators of the cell, converting oxygen and nutrients into adenosine triphosphate.

This feedback loop helps explain several health problems, ranging from cardiovascular disease as a result of sedentary lifestyles to more devastating conditions, such as multiple sclerosis and motor neuron disease.

Beyond medicine practice here on Earth, the findings could prove very important when planning future missions in space. The research shows that physical activity is critical in order to grow new neural cells and, as such, astronauts on long-term missions ought to perform load-bearing exercise daily. In the future, the researchers plan on studying the altered genes identified here in more depth.

The take-home message for the general public is that the physical inactivity is detrimental to our mental health,” co-author Dr. Daniele Bottai, also from the Università degli Studi di Milano, told ZME Science. 

“One could say our health is grounded on Earth in ways we are just beginning to understand,” concludes Bottai.

The findings appeared in the journal Frontiers in Neuroscience. 

People are more willing to accept embryonic stem cell research than politicians

As stem cell research continues to be a very divisive topic, a new study has revealed that the general public is much more willing to accept it than politicians.

Image in Public Domain.

The Swiss are very liberal with their referendums — they have quite a few every year. This offers a unique and direct perspective to see how voters think about a variety of topics including (in this case) embryonic stem cell research. They found that people were much more willing to accept the research than politicians.

“By analysing the outcomes of a referendum on a liberal new bill regulating such research, we reveal an about 10 percentage point lower conditional probability of the bill being accepted by politicians than by voters,” the study reads.

The motivations for the two categories of people are also quite different. For politicians, it’s all about the politics, whereas general people are swayed by different aspects.

“Whereas the behaviour of politicians is driven almost entirely by party affiliation, citizen votes are driven not only by party attachment but also by church attendance.”

Old and new

If you’ve kept up with stem cell research, you’re probably wondering why we’re talking about embryonic stem cell research (taking stem cells from embryos), when the science world is moving away to different types of stem cells, most notably induced pluripotent cells. Induced pluripotent stem cells are a type of pluripotent stem cell that can be generated directly from adult cells. But this study analyzed the 2004 referendum when embryonic stem cells stirred heated debates, and its conclusions are more about social science than biology.

The study showed that citizens care whether scientists are trustworthy, act transparently, and serve the public interest. Even scientists themselves have asked that journal editors and funding agencies enforce high standards of ethics. However, politicians play a different ball game. For them, it’s all about affiliation and, although this study doesn’t address it, personal interests.

“According to our findings, in this environment, citizens are more likely than politicians to favour embryonic stem cell research, suggesting that social discussion may help bring about agreement on shared principles, professional norms, and procedural conditions related to stem cell research. Citizen involvement through direct democracy might thus provide a way to bridge polarization in the stem cell debate.”

But as we all know, direct democracy is tricky and referendums can also backfire dramatically. The key here is an informed population. The people care about science and they want it kept to a good standard but they need to be accurately informed about the vote they are about to cast.

“Because of the high level of direct democracy in Switzerland, its citizens are generally well informed about upcoming referenda through intense public discourse and official booklets. These latter, which include the exact text of the legislative paragraphs to be modified or introduced into the law or constitution, provide objective information on the referendum issue.”

Journal Reference: David Stadelmann, Benno Torgler — Voting on Embryonic Stem Cell Research: Citizens More Supportive than Politicians. http://dx.doi.org/10.1371/journal.pone.0170656

 

Kris Boesen, pictured pulling weights three months after his surgery involving an experimental stem cell procedure. Credit: USC

Young man paralyzed from the neck down regains arm and hand movement following stem cell therapy

Kris Boesen, pictured pulling weights three months after his surgery involving an experimental stem cell procedure. Credit: USC

Kris Boesen, pictured pulling weights three months after his surgery involving an experimental stem cell procedure. Credit: USC

Six months ago, Kristopher (Kris) Boesen slammed into a telephone pole with his car after the vehicle fishtailed on the wet road. The traumatic injuries Kris sustained in the crash left him paralyzed from the neck down and doctors told the man’s parents there was a high risk he would remain so permanently.

“I couldn’t drink, couldn’t feed myself, couldn’t text or pretty much do anything, I was basically just existing. I wasn’t living my life, I was existing,” Kris said as he recounted the bleak days following his traumatic injury.

Faced with this prospect, Kris agreed to take part in an experimental neuroregenerative procedure developed by scientists at the USC Neurorestoration Center and Keck Medicine of USC. The 21-year-old had a novel treatment injected into the damaged cervical spine consisting of escalating doses of AST-OPC1 cells.

AST-OPC1 cells are made from embryonic stem cells which are coaxed to morph into oligodendrocyte progenitor cells (OPCs) — the cells found in the brain and spinal cord that support and replenish functioning nerve cells. Previous studies carried in a lab setting showed that AST-OPC1 stimulates vascularization and induces regeneration of denuded axons. This promotes the survival, regrowth, and conduction of nerve impulses in the injury site, the researchers say.

Only two weeks after his surgery, Kris began to show signs of improvement. Now three months after the procedure, he can now use a cell phone, operate a motorized wheelchair by himself, or hug friends and family. He can feel both arms and hands, something that lends hope that he can at least live independently.

“Now I have grip strength and do things like open a bottle of soda and feed myself. Whereas before I was relying on my parents, now after the stem cell therapy I am able to live my life.”

kris therapy stem cell

Credit: USC

Kris is one of three patients who was enrolled in the clinical trial run by Asterias Biotherapeutics. Each patient was injected with two million cells into their necks, but Kris was the first patient to receive more than ten million stem cells in April.

“Typically, spinal cord injury patients undergo surgery that stabilizes the spine but generally does very little to restore motor or sensory function,” explains Charles Liu, MD, PhD, director of the USC Neurorestoration Center. “With this study, we are testing a procedure that may improve neurological function, which could mean the difference between being permanently paralyzed and being able to use one’s arms and hands. Restoring that level of function could significantly improve the daily lives of patients with severe spinal injuries.”

The surgery improved motor function up to two spinal cord levels, which for Kris now means he can brush his teeth without assistance or operate a computer. Things he wasn’t able to do on his own prior treatment.

Researchers are don’t want to jump to any conclusions, though. It’s not unheard of for some people with the same kind of injury as Kris to make a partial recovery. It’s impossible to say at this time if the marked improvement is due to the stem cell therapy, but we’ll know for sure once more patients enroll in the trial. Future versions of the clinical trial might also tell us if this procedure can be used to regain leg function as well — maybe by injecting more stem cells and in another location along the injured spinal chord. Most importantly, these trials are meant to assess the safety of such procedure.

Besides stem cells, researchers working to help the paralyzed regain bodily functions are experimenting with virtual reality training, flexible spinal chord implants, spinal chord zapping with electricity, and brain-computer interfaces.

The Possibilities of Tailored Medical Treatments from IP Stem Cells and the Man Who Made it Possible

Imagine that we could scrape a few cells from our skin and send them to the lab. Within a few days, the lab would deliver a therapy or medicine specifically tailored to treat a devastating disease that we had unfortunately developed. These selfie-cells, programmed to treat our specific diseases, could be transplanted or injected on-site without the worry of immune rejection.

Shinya Yamanaka, photo by Rubenstein via Flickr.

Thanks to Dr. Shinya Yamanaka, a Nobel Prize-winning Japanese stem cell researcher, this customized treatment is in our near future. In 2006, he found that by using only a few genetic, nuclear factors, it was possible to take skin cells from mice and turn back the developmental clock. These cells reverted in potency to a status termed Induced Pluripotent Stem Cells (IPSCs). The creation of IPSCs has led researchers in regenerative medicine and drug discovery on an accelerated pathway with new methods to approach diseases.

While these IPSCs are similar to Embryonic Stem Cells (ESCs), they derive from the patient’s own skin. In essence, patients are the source of their own treatments.

The use of ESCs stirs ethical controversy because these cells source from an embryo. ESCs are totipotent, meaning that these cells have the ability to become any desired cell type. ESCs have the potential to develop an entire organism.

Lack of Federal Funding for ESC Research Led to Discovery of IPSCs

While ESCs are useful, they present more challenges for scientists to obtain and use them. From 2001 until 2009, it was not possible to obtain federal funding for any research that included ESCs. Researchers in many fields of science were forced to look for alternatives. Despite this eight-year funding ban, a silver lining emerged – it led to the discovery of IPSCs.

IPSCs are the next level of stem cell. Pluripotency implies the capacity for stem cells to become a number of different cell types, but that does not necessarily provide the ability to develop an entire organism. Induced with a set of factors, as Dr. Yamanaka showed, skin cells can turn back their state of potency or be reprogrammed.

It’s like turning back the developmental time clock in a fully differentiated cell. A cell that was once a skin fibroblast could now become a neuron if it was induced in a microenvironment. For example, it would now be possible to take skin cells from an Alzheimer’s disease patient and develop an in-vitro human cell culture model, since these cells can grow indefinitely. When the reprogramming occurs to create IPSCs, they become immortal, which is a key feature in their utility.

In the 10 years since Dr. Yamanaka discovered IPSCs, regenerative medicine and drug discovery-development have accelerated forward in the use of these cells. Diseases such as Alzheimer’s, Parkinson’s, Huntington’s and Down’s syndrome now have models that forego the use of ethically controversial ECSs. For drug screening and development, IPSCs are in use for in-vitro studies since these cells are capable of immortal growth in culture and provide genuine, human testable models. New drugs can be screened against cell culture models to determine their safety and efficacy, thanks to IPSCs.

IPSC Research Suggests Potential to Treat and Cure Incurable Diseases

Dr. Yamanaka was recognized for his contribution and awarded a Nobel Peace Prize in 2012 for his work that led to the discovery of IPSCs. Currently, Dr. Yamanaka and his team continue to probe the in-depth mechanisms of how somatic cells are reprogrammed to the pluripotency state.

As research efforts continue forward with IPSCs, we will see more models developed to study diseases, approaches to treat them and the development of new drugs. Perhaps in our not-so-distant future, the most remarkable step forward with IPSCs will be our own cells used to treat and cure diseases we once considered incurable.

About the Author

Dr. Christy A. Rothermund-Franklin is an associate professor for the school of STEM at American Public University. She earned her B.S. in biotechnology from the University of Nebraska and a Ph.D. in biochemistry and molecular biology from the University of Nebraska Medical Cente

Lab-Grown Kidneys Transplanted to Animals

For the first time, Japanese researchers have successfully grown a pair of kidneys in a lab and then transplanted them into animals. The organs functioned just fine, and this gives big hopes for the transplants ultimately moving to humans.

Dr. Takashi Yokoo and one of the test subjects. Image via CBS.

So far, they tried it on rats and pigs; the rats ones worked well right from the start, but it was more of a challenge moving on to a more advanced animal like a pig (pigs are actually similar to us biologically in a number of ways). The positive results that they reported on pigs actually raises hopes for human transplants.

Professor Chris Mason, an independent scientist based at University College London praised the study.

“This is an interesting step forward. The science looks strong and they have good data in animals.”

The artificial kidneys were created from embryonic stem cells, grown in the lab. Dr Takashi Yokoo and colleagues at the Jikei University School of Medicine in Tokyo also set a drainage tube and a bladder for the kidneys, to prevent them from swelling up and accumulating liquids. Urine first passes from the artificial kidney to the artificial bladder and then to the real bladder. Eight weeks later, when they checked their results, everything was still working fine.

However, while extremely promising, human trials are still years away. Mason added:

“This is an interesting step forward. The science looks strong and they have good data in animals. But that’s not to say this will work in humans. We are still years off that. It’s very much mechanistic. It moves us closer to understanding how the plumbing might work. At least with kidneys, we can dialyse patients for a while so there would be time to grow kidneys if that becomes possible.”

Journal Reference: Shinya Yokote et al, Urine excretion strategy for stem cell-generated embryonic kidneys. doi: 10.1073/pnas.1507803112

Stem Cell Treatment Offers Hope for MS Treatment

For the first time, scientists have developed a treatment for Multiple Sclerosis (MS) that actually reverses the disability. Dr. Richard K. Burt performed the first hematopoietic stem cell transplant (HSCT) for a multiple sclerosis (MS) patient in the United States at Chicago’s Northwestern Memorial Hospital, and the treatment showed great promise.

Normal cell vs Multiple Sclerosis Cell. Image via American Cryo system.

 

MS is an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a wide range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. It’s not clear what causes it and there is no clear treatment for the disease.

In this trial 151 patients underwent a stem cell transplant. Their immune systems were numbed first with low dose chemotherapy, and then doctors used stem cells previously extracted from the patients to “reboot” their immune systems. After only a few days spent in the hospital, the patients then returned home, reporting no symptoms from the disease and needing no more medication.

Doctors administered several tests to detect any lingering signs of the disease and also asked participants to fill out questionnaires regarding their lives. Four years after the treatment was administered, 80 percent of participants were relapse free, and even those who relapsed showed a significant reduction of symptoms.

Since 1993, the FDA has approved 12 disease-modifying therapies (DMTs) to treat relapsing-remitting MS (RRMS). All of them basically work around suppressing the immune system, and are extremely expensive – costing some $5,000 / months. They must also be taken indefinitely, since if you stop the treatment, there is a high risk for relapse. This treatment is also very expensive – it has a one time cost of $125,000, so it only starts paying for itself after 2 years.

“If you’re doing well on first-line therapies, interferons or Copaxone, good, that’s where you should stay,” Burt added. “But if you’re having frequent relapses, two or more a year despite those therapies … I think that’s the group that, rather than going to Tysabri or Fingolimod, should be given this therapy because it’s so much more beneficial. Plus, if you wait until you’ve had all those other [DMTs] then you increase the risk of this treatment.”

However, there is still much room for improvement with this type of stem cell treatment, and with further research, it might become significantly cheaper. But there are also downsides.

“The caveat,” Burt conceded, “is this is not effective in progressive MS.” He pointed out the tendency among neurologists to try one DMT after another until the patient is out of options before offering HSCT. “But by then [the patient has] entered secondary progressive and most likely nothing will help.”

This was also an observational cohort study, not a randomized controlled study. The journal article states:

Because this is an observational cohort without a control group, inferences about causal effects of HCST cannot be made. Definitive conclusions will require a randomized trial; however, this analysis provides the rationale, appropriate patient selection, and therapeutic approach for a randomized study.

In other words, while promising, this is an initial study with many limitations. A larger, more controlled study will almost certainly lead to better results, and then we can start talking about a treatment for MS.

The team is currently conducting a larger study comparing HSCT to FDA-approved DMTs at three centers worldwide. The trial is currently enrolling, and interested patients can learn more at http://www.stemcell-immunotherapy.com/research_clinical.html.

Journal Reference: Richard K. Burt et al. Association of Nonmyeloablative Hematopoietic Stem Cell Transplantation With Neurological Disability in Patients With Relapsing-Remitting Multiple Sclerosis JAMA. 2015;313(3):275-284. doi:10.1001/jama.2014.17986.

Open access paper.

Japanese woman is first recipient of next-generation stem cells

Researchers were able to grow sheets of retinal tissue from induced pluripotent stem cells, and have now implanted them for the first time in a patient.

Researchers were able to grow sheets of retinal tissue from induced pluripotent stem cells, and have now implanted them for the first time in a patient. RIKEN/Foundation for Biomedical Research and Innovation

A Japanese woman in her 70s is the world’s first recipient of cells derived from induced pluripotent stem cells, a technology that promises to work wonders and has the scientific community excited about the perspectives. Surgeons working on the case created the retinal tissue after reverting the patient’s own cells to ‘pluripotent’ state.

If you’d like to benefit from stem cells, but you’re worried that you haven’t had cells harvested early enough – then stop worrying, the next level technology is already here, offering the same advantages as embryo-derived cells but without some of the controversial aspects and safety concerns.

The two hour procedure took place a mere four days after the health-ministry committee gave Takahashi clearance to begin human trials; previously, it had been safely conducted on rats and mice. The surgery’s objective was transplanting a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells into an eye of an elderly Japanese woman suffering from age-related macular degeneration.

Yasuo Kurimoto of the Kobe City Medical Center General Hospital led the procedure, accompanied by a team of three other specialists.

“[She] took on all the risk that go with the treatment as well as the surgery”, Kurimoto said in a statement released by RIKEN. “I have deep respect for bravery she showed in resolving to go through with it.”

Kurimoto also took a moment to acknowledge the work of Yoshiki Sasai, a researcher who recently committed suicide. Yoshiki Sasai, deputy director of the RIKEN Center for Developmental Biology (CDB) in Kobe was one of the most brilliant minds working in stem cell research, but a scandal swirling around two stem-cell papers published in Nature in January had wreaked havoc on his career.

“This project could not have existed without the late Yoshiki Sasai’s research, which led the way to differentiating retinal tissue from stem cells.”

Sadly enough, Sasai’s downfall wasn’t even his own doing – one of his proteges, Haruko Obokata, then a visiting researcher, manipulated the results of two research papers on which Sasai also worked. In Japan, the media rained criticism on Sasai, including unsubstantiated accusations; despite the fact that he himself did not contribute to the forgery, he didn’t check the facts close enough. This immense pressure eventually led him to commit suicide.

Yoshiki Sasai. Nature.

But the results of his work are still alive today, and show much promise for future research. Even in a patient over 70 years old, the procedure will ensure that future degeneration doesn’t take place anymore, although it is less likely to restore vision to what it was before degeneration.

“We’ve taken a momentous first step toward regenerative medicine using iPS cells,” Takahashi said in a statement. “With this as a starting point, I definitely want to bring [iPS cell-based regenerative medicine] to as many people as possible.”

True Blood redux – artificial blood to be manufactured in factories

A few months ago we were telling you about the researchers from Transylvania, Romania, who developed artificial blood. Now, the production of blood on an industrial scale could become a reality as other researchers found a way to develop artificial blood from patients’ stem cells.

Photo: Alamy

Marc Turner, the principal researcher in the £5 million programme funded by the Wellcome Trust announced that his team had made red blood cells which are fit for human transfusion, and they will soon begin human trials. If everything goes fine in the human trials, they will soon start the mass production.

“Although similar research has been conducted elsewhere, this is the first time anybody has manufactured blood to the appropriate quality and safety standards for transfusion into a human being,” said Prof Turner.

The trials are to be concluded in late 2016 or early 2017, and will most likely involve the treatment of three patients with Thalassaemia – a rare blood disorder which requires regular transfusions. The patients will be treated with the newly produced blood and their evolution will be constantly monitored.

“The cells will be safe,” he said, adding that there are processes whereby cells can be removed.

If this project comes to fruition safely, then we could see the dawn of a new age in blood transfusions – with virtually limitless supplies of blood, which can save countless lives. They will focus on type O blood, which is universally accepted by all people.

“Although blood banks are well-stocked in the UK and transfusion has been largely safe since the Hepatitis B and HIV infections of the 1970s and 1980s, many parts of the world still have problems with transfusing blood,” said Prof Turner.

Economically, this is very feasible. The total costs, in the UK for a pint of blood transfusion is £120 ($200). With this method, the costs would be reduced significantly. Still, there are some technological hurdles which will have to be surpassed, but so far, things are sailing pretty smoothly.

Dr Ted Bianco, Director of Technology Transfer at the Wellcome Trust, said:

“One should not underestimate the challenge of translating the science into routine procedures for the clinic. Nowhere is this more apparent than in the challenge Professor Turner and colleagues have set out to address, which is to replace the human blood donor as the source of supply for life-saving transfusions.”

Rising Japanese scientist faked heralded stem cell research, lab says

Her short career was absolutely remarkable – before she was 20, Haruko Obokata was accepted into the science department at Tokyo’s Waseda University, but that was only the beginning. Then she studied at Harvard University in what was supposed to be a half-year program, but advisers were so impressed with her research, they asked her stay longer. It was there that her career would be defined – for better and for worse.

The research was called STAP — “stimulus-triggered acquisition of pluripotency” — which unveiled a new way to grow tissue. Needless to say, professors were impressed, and the scientific community was already treating her with respect – it was already shaping up to be a golden career.

“I think about my research all day long, including when I am taking a bath and when I am on a date with my boyfriend,” Obokata told the Asahi Shimbun.

After she got her PhD though, she published what appeared to be her groundbreaking research in the scientific journal Nature. Her paper focused around a new way to grow tissue and treat complicated diseases such as Parkinson’s – many people called it one of the most remarkable discoveries in stem cell research.

“There were many days when I wanted to give up on my research and cried all night long,” she said at news conference. “But I encouraged myself to hold on just for one more day.”

But as it turned out, her research was just castles of sand – fake castles of sand for that matter. Obokata’s research institute, Riken, announced that the 30-year-old had purposely fabricated the data to produce the findings. The Institute’s director Ryoji Noyori said he’ll “rigorously punish relevant people after procedures in a disciplinary committee,” making it very clear that Obokata will be the first to take a fall. ”The manipulation was used to improve the appearance of the results.”, he added.

Obokata, for her part, denied the month-long investigation’s allegations.

“I will file a complaint against Riken as it’s absolutely impossible for me to accept this,” AFP reports her saying in a statement.

But the evidence started piling up. Despite various efforts, no one was able to replicate the results she obtained, which is always a huge question mark – repeatability is at the very core of scientific research.

In early March one of the paper’s co-authors, Teruhiko Wakayama, jumped ship, calling for a retraction of the findings. He believes that the results were intentionally altered by Obokata.

“It’s unlikely that it was a careless mistake,” he wrote the Wall Street Journal in an e-mail. “There is no more credibility when there are such crucial mistakes,” he added.

The investigators say that the problem is with the images used in the study – DNA fragments submitted into Obokata’s work were modified, or entirely fabricated. So what will happen now ? The odds are, her doctorate will be stripped, as well as any other degree she worked so hard to obtain. She will most likely never be able to work in the scientific industry ever again. Everything that she worked so hard for, this brilliant mind, will be gone – and nothing will be left but a big, black stain – and the time and money wasted trying to recreate her fake results. I hope that investigators are wrong, and this will all turn out to be a big misunderstanding – but that’s unlikely to happen. It’s such a shame! I hope that in some way, she can still use her brilliant mind to contribute to science, and, should this be the case, make up for her mistakes.

 

Human brain artificially created in laboratory

Human embryonic stem cells can be induced into forming a developing brain tissue. The brain development process represents one of the most specific processes; during it, neuroepithelium, formed as a flat sheet by the nervous system, grows on the exterior layer of the embryo, after which it folds in to create a neural tube giving rise to the brain and the spinal cord. The process implicates the migration and proliferation of undeveloped nerve cells from the brain at one end and the spinal cord at the other.

Human embryonic stem cells spontaneously organize into neuroepithelial tissue containing multiple zones after growing for 70 days in culture. Via RIKEN.

The discovery made by Yoshiki Sasai, Taisuke KAdoshima and their colleagues from the RIKEN Center for Developmental Biology consisted in treating human embryonic stem (ES) cells using a system with signaling molecules that induce the formation of nervous tissue from the outer embryonic layer. The thesis of their scientific project was that the cells have the capacity of spontaneously organizing into cerebral cortical tissues – forming at the front of the developing neural tube.

The previous research of Sasai’s team had proven that a new culture technique could involve growing ES cells in suspension, showing that the cells are capable of self-organizing into complex three-dimensional structures. The finding served as a methodology throughout where pieces of cerebral cortex and embryonic eyes from mouse ES cells were grown. Another more recent study showed that there is a complete compatibility with human embryonic stem cells that can also organize into embryonic eyes that contain retinal tissue and light-sensitive cells.

The last study of Sasai’s team showed that the formation of nervous tissue from the outer embryonic layer can be induced by treating human ES cells to grow using the cell culture system with signaling molecules. This was doubled by the finding that the cells spontaneously organize into neuroepithelial tissue which folds up immediately after this, to give a multilayered cortex.

During the thickening of the front end of the neural tube, simultaneous with embryonic development at both ends, waves of cells migrate outward to mold the layered cerebral cortex as well as other parts of the brain. By correlation the study found that the reason why the front end of the neural tube thickens is the growth of the glial fiber, spanning the thickness of the tube and guiding migrating cells.

Another critical difference highlighted by the research between the development of the neuronal tube in mice in humans is that in humans the inner surfaces of the neural tube and the intermediate neuroepithelial zone underneath it contain distinct populations of neural progenitors resembling radial glia. In contrast, the progenitor population in mice and rats is not present in the developing of the cortex. Kadoshima declared that ‘efficient generation of cortical tissues could provide a valuable resource of functional neurons and tissues for medical applications’, suggesting that further research should combine this method with disease-specific human induced pluripotent SE cells, while the reproduction of complex human disorders is also a possible on the table for further experiments.

Stem Cell therapy could help us grow back fingers

Mammals can naturally regenerate the very top of their fingers and toes after amputation; starting from this idea, researchers have demonstrated the mechanism that describes this process, and explain how stem cells from nails could play a pivotal role in future regeneration of entire fingers.

fingers

A study conducted on mice showed that the chemical signal that triggers stem cells to develop into new nail tissue also attracts nerves that promote bone and nerve regeneration. The study suggests that nail stem cells could be used to develop new regeneration treatments for amputees.

Mice are pretty similar to humans in thhis regard – in both species, regenerating a finger starts with regenerating the nail. But whether the amputated portion of the digit actually takes place depends on exactly where the amputation occurs – if the stem cells in the nails are amputated as well, then no regeneration takes place. But if a small portion of the nail still remains in place, then it does regenerate. To understand exactly why these stem cells are so important, researchers turned to mice.

The two unfortunate groups of mice were separated into two groups – one control group, and one which was treated with a drug that made them unable to make the signals for new nail cells to develop. The second group was unable to regenerate, while the first one did this just fine, in time. When the signal was replenished, the second group resumed regeneration.

Limb regeneration is a very interesting field for biologists at the moment; a vast number of animals can regenerate lost limbs, most notably amphibians – aquatic salamanders can regenerate complete limbs, and even parts of their heart, by a process which involves their immune system. By studying species which are close to us and understanding the mechanism through which they regenerate, we could some day apply the same techniques to humans.

Via Discovery

Skin cells of a monkey reverse engineered into stem cells

Researchers have managed to take skin cells from monkeys, reverse engineer them into stem cells, and then transplant into the monkeys’ brain where they successfully became brain cells. This technique holds massive promise for treating mental degenerative diseases.

schame

The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Using Rhesus monkeys iPSC-derived neural progenitors, they developed neurons, astrocytes, and myelinating oligodendrocytes (all types of brain cells).

This was done in primates, which are obviously closer to us than rats – and closer to humans is always better. Also, this method created no tumor formation in vivo, nor any other type of negative immune response.

The main problem with this study is that they did not see any functional improvement after transplantation based on behavioral recovery or PET data. Also, while the study is a proof of concept, it still isn’t very comprehensive. They showed that differentiated cells can engraft successfully into their injured brain region. No functional recovery occurred (yet), but what’s really really good is that no tumors were caused as well.

Stem cell research: win some, lose some

Stem cell research is still extremely controversial and problematic due to the numerous financial, social, and political pressures often applied on this kind of study. However, as some of the biggest companies working in the field throw the towel, others claim they will not stop their pioneering work, that bring eyesight to the blind and cure broken hearts (literally).

Scientists worldwide were shocked U.S. biotech company Geron Corp announced on Monday they will quit stem cell research, blaming this decision on the lack of money and the complexities of getting regulatory approval. However, teams working on less ambitious adult stem cells project are doing just fine.

“It’s a tale of two ends of the market. I believe the adult stem cell space was always more attractive anyway,” said Navid Malik, a biotechnology analyst at Merchant Securities.

However, science has received a significant blow with the shutdown of this company. Stem cell treatment offers a totally unique and revolutionary way of treating diseases and a number of conditions, which are otherwise incurable and cause the suffering and death of millions. Heart diseases, Parkinsons, kidney failure – these are just a few of the ones that could be helped by this revolutionary treatment.

What happens is embryonic stem cells are harvested from embryos and have the potential to become almost any type of tissue; on the other hand, adult stem cells are less controversial (because they come from adults), but they are also much less flexible, and can only become a number of tissues.

In a more advanced study, researchers were testing an embryonic stem cell treatment aimed at helping patients with spinal cord injuries like the late Superman actor Christopher Reeves – who was paralyzed in an accident.

Making superman walk would have been great for business but was an ambitious target for a serious problem and maybe not the best start scientifically or clinically for stem cell therapies,” said Alison Murdoch, head of the fertility center at Britain’s Newcastle University.

What do you think about embryonic stem cell research ? I’ve asked myself and the ones around me this question numerous times, and I’ve received the most varied and surprising answers.

Via Reuters

Vatican teams up with US biotech firm to shift focus off embryo research

The Vatican have entered an unusual partnership with a relatively small U.S. biotech company (NeoStem) to promote using adult stem cells for treating diseases, instead of focusing on embryonic stem cell research.

The Vatican are perhaps the loudest advocates of not using embryonic stem cells; the Christian teaching holds that the life begins at conception, and as a result, in their view, the loss of embryonic cells equals death.

The partnership will be marked by a conference which will be held in New York, bringing together researchers and cardinals; this initiative is part of the Vatican’s recent $1 million, five-year initiative to promote adult stem cell therapies and research and shift people’s attention from embryonic research. From their point of view, this is a lofty goal, but I’m not sure $1 million in five years will get you very far when dealing with this kind of objective.

Transplant of adult stem cells are already common in treating people with serious illnesses, but many believe that the more flexible and useful embryonic cells are the true key that should be used. Lots of work has and will be put in both camps, but it’s obvious that things are moving in the right direction, and without the usual bureaucracy and obtuse thinking, we would already be a few steps ahead of where we are now.

First trial of embryonic stem cells in humans

In was is a historic day, US doctors have officially begun the first trial of using human embryonic stem cells, as a result of the green light they got from regulators. The controversial method has been on the table for quite a while, and now The Food and Drug Administration has given a license to Geron to use stem cells to treat people with spinal injuries. These cells have the potential of becoming virtually any cell needed, including nerve cells.

Geron, the corporation who will lead this pivotal research is based in “silicon valley”, has spent 170 million dollars to develop a treatment for spinal cord injuries and reported that after the stem cell treatment, paralyzed rats regained some of their movement. However, it is still not yet clear how well people will respond to this kind of treatment; researchers are optimistic and they have already started human trials.

“When we started working with human embryonic stem cells in 1999, many predicted that it would be a number of decades before a cell therapy would be approved for human clinical trials. This accomplishment results from extensive research and development and a succession of inventive steps.”

And a great accomplishment it is ! Hopefully, this will be just the first step, and stem cells will be applied in other sorts of clinical trials too, because the huge potential they have cannot be neglected. Still, it will take some time to see results.

Professor Sir Ian Wilmut, director of the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh, said:

“This is very exciting news, however, it is very important to appreciate that the objective of trials at this stage is to confirm first of all that no harm is done to patients, rather than to look for benefits. Once that has been confirmed then the focus moves on to development and assessment of the new treatment.”

“This is indeed a significant milestone in our journey towards the promise of stem cell-based medicines. The global stem cell and regenerative medicine community will be awaiting the results of this safety trial with much anticipation.”, added Ben Sykes, executive director of the UK National Stem Cell Network

Human Embryonic Stem Cell Lines Created Without The Destruction Of Embryos

stem cells
The ethical and moral aspects of using stem cells have been discussed a lot and it seems there is no good answer; genetic practically has no limit and since the discovery of DNA things have evolved very quickly. But the thing is that the moral aspects concerning it could be left unsolved and yet everybody could be happy. How?

Well what if we could use stem cells without causing vital damage to the embryos? That would pretty much solve things; and we are not so far away from that. Advanced Cell Technology, Inc. together with colleagues announced the development of five human embryonic stem cell (hESC) lines without the destruction of embryos.

In fact, the NIH report to the President refers to this technology as one of the viable alternatives to the destruction of embryos. The method was published January 11 in the journal Cell Stem Cells, published by Cell Press. What they did is that they removed single cells from the embryo using a technique similar to preimplantation genetic diagnosis (PGD). The biopsied embryos continued to develop normally and were then frozen. After that the cells which were removed were cultured utilizing a special method which recreates the optimal developmental environment and it has a substantially improved efficiency of deriving stem cells to rates comparable to using the traditional approach of deriving stem cells from the inner cell mass of a whole blastocyst stage embryo.

“This is a working technology that exists here and now,” said Robert Lanza, M.D., Chief Scientific Officer at Advanced Cell Technology and senior author of the paper. “It could be used to increase the number of stem cell lines available to federal researchers immediately. We could send these cells out to researchers tomorrow. If the White House approves this new methodology, researchers could effectively double or triple the number of stem cell lines available within a few months. Too many needless deaths continue to occur while this research is being held up. I hope the President will act now and approve these stem cell lines quickly.”

The results sound promising but it is hard to say how things are going to turn out. We will wait and see.