Stem Cell Clinic

Nobel Prize goes to pioneers of induced stem cell research

John Gurdon and Shinya Yamanaka were jointly awarded the Nobel Prize in Physiology or Medicine on Monday for their research on resetting cells to their earliest developmental stages.The work has yet to yield a clear breakthrough in medical treatment, but it has revolutionized scientists ability to study both normal and diseased development.

Gurdon, 79, performed his seminal work in the late 1950s and early 1960sa good deal of it before Yamanaka was born. In his most famous study, Gurdon showed that replacing the nucleus of an adult cell with the nucleus of an embryonic cell reset the adult cell to an embryonic state: Many of the cells became tadpoles. This strongly suggested that embryonic-state DNA and the molecules that controlled gene expression in the nucleus were sufficient to make a cell "pluripotent" againor capable of turning into any type of tissue in the body.

Some40 years later, Yamanaka took this further by showing that adult mouse skin cells could be reset to their embryonic state just by adding a set of genes into the cells nuclei, and he later reduced this number to just four genes. The cells are now referred to as induced pluripotent stem cells, or iPS cells, and are a common tool in the study of development and disease.

With Yamanakas discovery, researchers suddenly had a way of studying pluripotent stem cells without destroying embryosa limitation that had caused countless headaches at the time of Yamanakas breakthrough, as President George W. Bush had instituted severe limitations on such research.

Since Yamanakas seminal finding, researchers have used the approach to demonstrate some stunning feats: They have turned the skin cells of people who have Parkinsons disease into disease in a dish models that allow them to watch the development of the disease over time and to observe what genes go wrong when and why, and, just last week, a team of scientists published research that used the approach to turn mouse skin cells back into mouse eggs, which then produced baby mice.

The technique has not been without complications: Because one of the four genes is also highly implicated in cancer, the iPS cells are more likely to become cancerous than true embryonic stem cells. The issue has slowed research in the field.

Today, Gurdon works at the Gurdon Institute in Cambridge, England, which he founded, and Yamanaka has appointments at UC San Franciscos Gladstone Institute and at Kyoto University.

You can read all about the winners here.

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Nobel Prize goes to pioneers of induced stem cell research

Stem cell pioneers take first prize in Nobel week

This year's Nobel Prize for Medicine goes to...

The 2012 Nobel Prize for medicine has been awarded to stem cell researchers John Gurdon and Shinya Yamanaka of Britain and Japan. They take the first Nobel prize of the year, with a flurry to follow over the next week.

Judges in Stockholm said on Monday that the medicine prize had been awarded to the researchers "for the discovery that mature cells can be reprogrammed to become pluripotent," saying that this discovery had "revolutionized our understanding of how cells and organisms develop."

Gurdon and Yamanaka are stem cell researchers who are seeking ways to obtain embryonic stem cells - a kind of genetic blank slate, cells that can be 'programmed' to take on many different forms and perform different functions - from the cells of an adult. Embryos themselves are another more controversial source of stem cells.

"We are trying to find ways of obtaining embryo cells from the cells of an adult," Gurdon writes on his Gurdon Institute website. "The eventual aim is to provide replacement cells of all kinds starting from usually obtainable cells of an adult individual."

A Nobel Prize medal on display in Stockholm

The British scientist also said such a system was advantageous because the stem cells could be obtained from the patient themselves, reducing the risk of rejection when they were employed as a treatment.

The medals will be doled out in December, the winners named in the next few days

Stem cells appear to have potential to treat a wide range of illnesses, with a major barrier to the research the ethical implications of obtaining the cells from unborn foetuses.

A busy week in the Swedish capital

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Stem cell pioneers take first prize in Nobel week

Nobel winner Yamanaka a stem cell pioneer

SHINYA Yamanaka could have made bits of sewing machines for a living. Instead, his tinkering with the building blocks of life has made him a Nobel prize winner.

Born in 1962 in a Japan beginning a decades-long manufacturing boom, Yamanaka was the only son of a factory owner who produced parts for sewing machines.

But even as the country's industries exploded in the 1970s, his father told him he should not follow the traditional Japanese path and take over the family business, but become a doctor.

Half a century later and after a stint as an orthopaedic surgeon, he is a leading authority on how cells work.

Kyoto University-based Yamanaka was being celebrated on Monday for his work, alongside Briton John Gurdon, on how cells can be reprogrammed.

So-called "nuclear reprogramming" uses a fully-developed adult cell to create a stem cell - a kind of blank slate that has the potential to become any other kind of cell in the body.

Scientists say in this way they can generate materials either to experiment on, or to use within the body - perhaps as a means of repairing or even replacing damaged or diseased organs.

Gurdon's work proved that mature cells maintain the "memory" of what they could have been; a brain cell that specialises in transmitting messages retains its ability to absorb nutrients like a cell in the wall of the intestine.

To do this, he took the nucleus from a specialised cell and implanted it into an egg without a nucleus. Allowed to develop naturally, this becomes an early-stage embryo containing stem cells.

Harvesting those cells necessitates the destruction of that embryo.

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Nobel winner Yamanaka a stem cell pioneer

Stem cell pioneers win Nobel for medicine

STOCKHOLM (AFP) - Shinya Yamanaka of Japan and John Gurdon of Britain won the Nobel Prize on Monday for work in cell programming, a frontier that has raised dreams of replacement tissue for people crippled by disease.

The two scientists found that adult cells can be transformed back to an infant state called stem cells, the the key ingredient in the vision of regenerative medicine.

"Their findings have revolutionised our understanding of how cells and organisms develop," the Nobel jury declared. "By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy."

Among those who acclaimed the award were Britain's Royal Society, Ian Wilmut, "father" of Dolly the cloned sheep, and a leading ethicist, who said it eased a storm about the use of embryonic cells.

Stem cells are precursor cells which differentiate into the various organs of the body.

They have stirred huge excitement, with hopes that they can be coaxed into growing into replacement tissue for victims of Alzheimer's, Parkinson's and other diseases.

Gurdon, 79, said he was grateful but also surprised by the honour, since his main research was done more than 40 years ago.

In 1962, he discovered that the DNA code in the nucleus of an adult frog cell held all the information to develop into every kind of cell.

This meant that an adult cell could in essence be reprogrammed.

His landmark discovery was initially met with scepticism, as the journey from immature to specialised cell was previously deemed irreversible.

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Stem cell pioneers win Nobel for medicine

Stem cell pioneers win Nobel medicine honors

The 2012 Nobel Prize for medicine has been awarded to stem cell researchers John Gurdon and Shinya Yamanaka of Britain and Japan. They take the first Nobel prize of the year, with a flurry to follow over the next week.

Judges in Stockholm said on Monday that the medicine prize had been awarded to the researchers "for the discovery that mature cells can be reprogrammed to become pluripotent," saying that this discovery had "revolutionized our understanding of how cells and organisms develop."

Gurdon and Yamanaka are stem cell researchers who are seeking ways to obtain embryonic stem cells - a kind of genetic blank slate, cells that can be 'programmed' to take on many different forms and perform different functions - from the cells of an adult. Embryos themselves are another more controversial source of stem cells.

"We are trying to find ways of obtaining embryo cells from the cells of an adult," Gurdon writes on his Gurdon Institute website. "The eventual aim is to provide replacement cells of all kinds starting from usually obtainable cells of an adult individual."

The British scientist also said such a system was advantageous because the stem cells could be obtained from the patient themselves, reducing the risk of rejection when they were employed as a treatment.

The medals will be doled out in December, the winners named in the next few days

Stem cells appear to have potential to treat a wide range of illnesses, with a major barrier to the research the ethical implications of obtaining the cells from unborn foetuses.

A busy week in the Swedish capital

This year's laureates in the field of physics will be named on Tuesday, with chemistry following on Wednesday and perhaps the most famous Nobel Peace Prize to be awarded on Friday. As is tradition, there is no set date for the Nobel Prize for Literature - but that will almost certainly fill the gap in the schedule on Thursday. The economics prize winner or winners will be named on October 15.

All the prizes will be awarded in Stockholm simultaneously at a December 10 ceremony.

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Stem cell pioneers win Nobel medicine honors

Milestones in Stem Cell Science

Gail Martin, PhD

Since 1981, when UCSFs Gail Martin, PhD, co-discovered embryonic stem cells in mice and coined the term embryonic stem cell, UCSF has been a key player in the stem cell field.

The success in 1998 by the University of Wisconsins James Thomson in deriving human embryonic stem cells from embryos propelled the stem cell research field forward.

Beginning in the late 1990s, UCSFs Roger Pedersen, PhD, was one of two University scientists nationwide the other being James Thomson, DVM, PhD, of the University of Wisconsin to pioneer the human embryonic stem cell field. Following Thomsons 1998 discovery of a technique for deriving human embryonic stem cells from donated embryos left over following in vitro fertilization efforts, Pedersens lab derived two of its own lines of cells using the same technique.

In 2006, Shinya Yamanaka, MD, PhD, a senior investigator and the L.K. Whittier Foundation Investigator in Stem Cell Biology at the Gladstone Institute of Cardiovascular Disease and a professor of anatomy at UCSF, developed the method for inducing skin cells from mice into becoming like pluripotent stem cells and called them iPS cells. In 2007, Yamanaka did the same with adult human skin cells.

Shinya Yamanaka, MD, PhD

Yamanakas experiments revealed that adult skin cells, when treated with four pieces of DNA (now called the Yamanaka factors), can induce skin cells to revert back to their pluripotent state. His discovery has since led to a variety of methods for reprogramming adult cells into stem cells that can become virtually any cell type such as a beating heart cell or a neuron that can transmit chemical signals in the brain. This allows researchers to create patient-specific cell lines that can be studied and used in everything from drug therapies to regenerative medicine.In between and since, there has been major progress in scientists understanding of stem cells.

Today, fueled in part by the robust research enterprise at UCSF, the field is burgeoning. Yamanaka now commutes between Japan and San Francisco, where he is a professor of anatomy at UCSF and a senior investigator at the UCSF-affiliated J. David Gladstone Institute for Cardiovascular Disease.

At UCSF, Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, leads one of the largest and most comprehensive programs of its kind in the United States.

In about 125 labs, basic science researchers carry out studies in cell culture and animals aimed at understanding healthy cell function and disease progression and developing treatment strategies for a broad spectrum of disorders, including heart disease, diabetes, neurological diseases such as epilepsy, multiple sclerosis, Parkinsons disease and spinal cord injury and cancer. Clinical research teams have begun one of the first early-stage stem cell clinical trials in the United States, and other potential trials are on the horizon.

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Milestones in Stem Cell Science

Cellerant Awarded SBIR Contract Funding to Develop CLT-009 for Treatment of Thrombocytopenia

SAN CARLOS, Calif.--(BUSINESS WIRE)--

Cellerant Therapeutics Inc., a biotechnology company developing novel hematopoietic stem cell-based cellular and antibody therapies for blood disorders and cancer, announced today that it has been awarded a Small Business Innovation Research (SBIR) Phase 1 contract and a Phase 2 option from the National Cancer Institute (NCI) valued up to $1,683,503. The SBIR Contract funds the development of CLT-009, a first-in-class, human allogeneic Megakaryocyte Progenitor Cell therapy for the treatment of thrombocytopenia in cancer patients and allows the Company to conduct studies to enable an Investigational New Drug (IND) Application to be filed with the FDA in the next two years.

Thrombocytopenia is characterized as a significant reduction in the concentration of circulating platelets. Platelets are crucial in the process of coagulation to stop bleeding, and thrombocytopenia can increase the risk of severe bleeding in patients. It is becoming an increasingly common problem among oncology patients and a significant dose-limiting toxicity, especially in the treatment of hematological malignancies. Chemotherapy and radiation therapy are the most common causes of thrombocytopenia because the platelet-producing cells, megakaryocytes, and their precursors are highly sensitive to myelosuppressive cytotoxics and ionizing radiation. Thrombocytopenia typically occurs during the initial cycles of high-dose chemotherapy and radiation therapy, usually 614 days after administration. According to Datamonitor, the estimated incidence of cancer patients who suffer from significant chemotherapy-induced thrombocytopenia worldwide was approximately 200,000 in 2008.

Occurrence of severe thrombocytopenia may require dose reductions for chemotherapy regimens which can impact subsequent disease control and survival, especially in the treatment of hematological malignancies such as acute leukemia and high-risk myelodysplastic syndrome. Current treatment options include platelet transfusions which are costly and labor intensive and are associated with risks such as contamination and transmission of viral and bacterial infections. Recombinant human interleukin-11 is the only approved agent for chemotherapy induced thrombocytopenia but its use is limited and has only modest efficacy and significant side effects. CLT-009, a human Megakaryocyte Progenitor Cell product, would be an alternative treatment option, providing the critical megakayocyte progenitor cellular support to rapidly produce platelets in vivo and shorten the duration of severe thrombocytopenia following chemotherapy treatment.

We are delighted to receive this contract from NCI to support the development of our novel, off-the-shelf, platelet product and address a high unmet need, said Ram Mandalam, Ph.D., President and Chief Executive Officer of Cellerant Therapeutics. This contract allows us to not only leverage our experience in developing cellular therapies but also provides us with the ability to bring CLT-009 closer to the clinic. Our unique product portfolio, which now includes CLT-009, along with our CLT-008 myeloid progenitor cell product and our therapeutic antibodies targeting cancer stem cells, demonstrates our continued commitment to developing novel products for the benefit of cancer patients.

In addition to this SBIR contract, Cellerant has previously received grants from the National Institute of Health (NIH) in 2008 2010 to conduct research studies in platelet recovery which it has successfully completed. In its previous studies, Cellerant demonstrated that megakaryocyte progenitor cells were able to produce human platelets in preclinical models with in vivo functionality similar to that of normal human platelets.

This program is funded with Federal funds from the National Institute of Health, Department of Health and Human Services, under Contract No.HHSN261201200076C.

About CLT-009

CLT-009 is a unique, off-the-shelf, cryopreserved, cell-based therapy that contains human Megakaryocyte Progenitor Cells derived from adult hematopoietic stem cells that have the ability to mature into functional platelets in vivo. Cellerant is developing CLT-009 as an effective treatment for chemotherapy and radiation-induced thrombocytopenia in cancer patients.

About Cellerant Therapeutics

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Cellerant Awarded SBIR Contract Funding to Develop CLT-009 for Treatment of Thrombocytopenia

Stem Cell Discovery Secures Nobel Prize

By: Jenny Marder

Nobel Prize winner Sir John Gurdon talks to reporters on Oct. 8, 2012 in London. Gurdon and Shinya Yamanaka from Japan have both been awarded the Nobel prize for medicine or physiology for their work as pioneers of stem cell research. Photo by Peter Macdiarmid/Getty Images.

In 1962, John B. Gurdon of the United Kingdom discovered that a cell removed from the gut of a frog contained all the genetic information necessary to create the whole frog. More than 40 years later, Shinya Yamanaka of Japan found that by introducing a few genes to a mature mouse cell, he could reprogram it into a stem cell, capable of developing into any cell in the body.

Gurdon and Yamanaka share this year's Nobel Prize in Medicine and Physiology for their work in cellular reprogramming, 50 years after Gurdon's initial discovery. Their work in stem cells has led to a wave of advances, from cloning to allowing scientists to create embryonic cells without having to destroy embryos.

Gurdon was still a graduate student when he first transplanted genetic information from the nucleus of an intestinal cell of one frog into the fertilized egg cell of another. That cell went on to develop into a tadpole, proving that even mature, specialized cells have all the information needed to transform an embryo into an adult.

He relied on a technique called nuclear transfer to transplant the nuclei. The discovery flew in the face of established opinion, since other more established scientists hadn't been able to successfully make such a transfer, and it was thought then that a specialized cell is irreversibly tied to its fate.

"We had to go through a few years, in a sense, of letting the results sink in," Gurdon said in an early morning interview with the Nobel committee.

The same year that discovery was published, Yamanuka was born. And 40 years later, he took the science a big step farther. His research identified the four genes that made it possible to reverse mature stem cells into their embryonic state without using nuclear transfer. The "induced pluripotent embryonic stem cells" could then go on to become nerve cells, heart cells, gut cells.

That finding opened the possibility for skin cells to be reversed to embryonic cells and then reprogrammed into nerve, heart or other tissue cells for medical uses and disease treatment. Such reprogrammed cells have not yet been used to treat patients.

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Stem Cell Discovery Secures Nobel Prize