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Significant milestone in stem cell research at The Wellcome Trust – Medical Research Council institute

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Scientists are celebrating a breakthrough in stem cell research.

A type of human stem cell has been replicated in a lab for the first time in history.

The cells, previously impossible to duplicate, have been recreated to the equivalent of those between seven and nine days old the same as found in an embryo before it implants in the womb.

The creation of the human pluripotent cells opens a door for specialised cells to be created in the future for use in regenerative medicine.

The Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute led the research, which was carried out by both British and Japanese academics.

Professor Austin Smith, director, said: "Our findings suggest that it is possible to rewind the clock to achieve true ground state pluripotency in human cells.

"These cells may represent the real starting point for formation of tissues in the human embryo. We hope that in time they will allow us to unlock the fundamental biology of early development, which is impossible to study directly in people."

The "reset" cells could be used as "raw material" for therapies, as well as diagnostic tools and drug screenings.

Scientists also hope that after further studying, the cells will help them learn more about how an embryo develops correctly, and how miscarriages and developmental disorders are caused.

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Significant milestone in stem cell research at The Wellcome Trust - Medical Research Council institute

Stem cell advance made by Cambridge scientists

Cambridge scientists have successfully reset human pluripotent stem cells to the earliest developmental state equivalent to cells found in an 7-9 day old embryo before it implants in the womb.

The researchers believe that these pristine stem cells, which have until now been impossible to replicate in the lab, could mark the true starting point for human development.

It is hoped that the discovery, published in Cell, will lead to a better understanding of human development and could in future allow the production of safe and more reproducible starting materials for a wide range of applications including cell therapies.

Researchers led by the Wellcome Trust-Medical Research Council (MRC) Cambridge Stem Cell Institute at the University of Cambridge, have managed to induce a ground state by rewiring the genetic circuitry in human embryonic and induced pluripotent stem cells. Their reset cells share many of the characteristics of authentic nave embryonic stem cells isolated from mice, suggesting that they represent the earliest stage of development.

Human pluripotent stem cells, which have the potential to become any of the cells and tissues in the body, can be made in the lab either from cells extracted from a very early stage embryo or from adult cells that have been induced into a pluripotent state.

To date, scientists have struggled to generate human pluripotent stem cells that are truly pristine researchers have only been able to derive cells which have advanced slightly further down the developmental pathway. These bear some of the early hallmarks of differentiation into distinct cell types theyre not a truly blank slate. This may explain why existing human pluripotent stem cell lines often exhibit a bias towards producing certain tissue types in the laboratory.

Capturing embryonic stem cells is like stopping the developmental clock at the precise moment before they begin to turn into distinct cells and tissues, explains Professor Austin Smith, Director of the Stem Cell Institute, who co-authored the paper.

Scientists have perfected a reliable way of doing this with mouse cells, but human cells have proved more difficult to arrest and show subtle differences between the individual cells. Its as if the developmental clock has not stopped at the same time and some cells are a few minutes ahead of others.

The process of generating stem cells in the lab is easier to control in mouse cells, which can be frozen in a state of nave pluripotency using a protein called LIF. Human cells are not as responsive to LIF, so they must be controlled in a different way that involves switching key genes on and off. For this reason scientists have been unable to generate human pluripotent cells that are as primitive or as consistent as mouse embryonic stem cells.

The researchers overcame this problem by introducing two genes NANOG and KLF2 causing the network of genes that control the cell to reboot and induce the nave pluripotent state. Importantly, the introduced genes only need to be present for a short time. Then, like other stem cells, reset cells can self-renew indefinitely to produce large numbers, are stable and can differentiate into other cell types, including nerve and heart cells.

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Stem cell advance made by Cambridge scientists

World's first lab grown stem cells implanted

Tokyo, Sep 13 (IANS): Japanese researchers have successfully implanted lab-grown retinal tissue from induced pluripotent stem cells (iPS) into a woman in her 70s - the world's first recipient of stem cells.

In a two-hour procedure, a team of three eye specialists led by Yasuo Kurimoto of the Kobe City Medical Center General Hospital transplanted a 1.3 by 3.0 millimetre sheet of retinal pigment epithelium cells into an eye of the woman who was suffering from an age-related macular degeneration.

The procedure was performed at the Institute of Biomedical Research and Innovation Hospital, next to the RIKEN Center for Developmental Biology (CDB) where ophthalmologist Masayo Takahashi had developed and tested the cells.

Kurimoto performed the procedure in a mere four days after a health ministry committee gave Takahashi clearance for the human trials, the scientific journal Nature reported.

She took the patient's skin cells, converted them into iPS cells and then coaxed them to differentiate into retinal cells.

The patient experienced no effusive bleeding or other serious problems.

"The patient took on all the risks that came along with treatment and surgery. I have deep respect for the bravery she showed in resolving to go through with it," Kurimoto said in a statement.

Kurimoto also thanked Shinya Yamanaka, a stem-cell scientist at the Kyoto University "without whose discovery of iPS cells, this clinical research would not be possible".

Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for his work.

"We have taken a momentous first step toward regenerative medicine using iPS cells," Takahashi concluded.

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World's first lab grown stem cells implanted

Japan carries out first iPS stem cell retina surgery

TOKYO: Japanese researchers on Friday (Sep 12) conducted the world's first surgery to implant "iPS" stem cells in a human body in a major boost to regenerative medicine, two institutions involved said.

A female patient in her 70s with age-related macular degeneration (AMD), a common medical condition that can lead to blindness in older people, had a sheet of retina cells that had been created from iPS cells implanted. "It is the first time in the world that iPS cells have been transplanted into a human body," a spokeswoman for Riken, one of the research institutions, told AFP.

The research team used induced Pluripotent Stem (iPS) cells - which have the potential to develop into any cell in the body - that had originally come from the skin of the patient. Until the discovery of iPS several years ago, the only way to obtain stem cells was to harvest them from human embryos.

"We feel very much relieved," ophthalmologist Masayo Takahashi, the leader of the project at Riken, told a news conference after the surgery in Kobe. "We want to take it as a big step forward. But we must go on and on from here."

In a statement, the institution said that "no serious adverse phenomena such as excessive bleeding occurred" during the two-hour procedure. The surgery is still at an experimental stage, but if it is successful, doctors hope it will stop the deterioration in vision that comes with AMD.

The patient - one of six expected to take part in the trial - will be monitored over the next four years to determine how well the implants have performed, whether the body has accepted them and if they have become cancerous.

AMD, a condition that is incurable at present, affects mostly middle-aged and older people and can lead to blindness. It afflicts around 700,000 people in Japan alone.

The study was being carried out by researchers from government-backed research institution Riken and the Institute of Biomedical Research and Innovation Hospital.

Stem cell research is a pioneering field that has excited many in the scientific community with the potential they believe it offers. Stem cells are infant cells that can develop into any part of the body. Harvesting from human embryos is controversial because it requires the destruction of the embryo, a process to which religious conservatives, among others, object.

Groundbreaking work done in 2006 by Shinya Yamanaka at Kyoto University, a Nobel Laureate in medicine last year, succeeded in generating stem cells from adult skin tissue.

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Japan carries out first iPS stem cell retina surgery

Next-Generation Stem Cells Transplanted in Human for the First Time

Surgeons implanted retinal tissue created after reverting the patient's own cells to a "pluripotent" state

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. Credit: 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 has created great expectations since it could offer the same advantages as embryo-derived cells but without some of the controversial aspects and safety concerns.

In a two-hour procedure starting at 14:20 local time today, a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration.

The procedure took place at the Institute of Biomedical Research and Innovation Hospital, next to the RIKEN Center for Developmental Biology (CDB) where ophthalmologist Masayo Takahashi had developed and tested the epithelium sheets. She derived them from the patient's skin cells, after producing induced pluripotent stem (iPS) cells and then getting them to differentiate into retinal cells.

Afterwards, the patient experienced no effusive bleeding or other serious problems, RIKEN has reported.

The patient 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.

He hit a somber note in thankingYoshiki Sasai, a CDB researcher who recenty committed suicide. This project could not have existed without the late Yoshiki Sasais research, which led the way to differentiating retinal tissue from stem cells.

Kurimoto also thanked Shinya Yamanaka, a stem-cell scientist at Kyoto University without whose discovery of iPS cells, this clinical research would not be possible. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for that work.

Kurimoto performed the procedure a mere four days after a health-ministry committee gave Takahashi clearance for the human trials (see 'Next-generation stem cells cleared for human trial').

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Next-Generation Stem Cells Transplanted in Human for the First Time

Woman Receives First Stem Cell Therapy Using Her Own Skin Cells

TIME Health medicine Woman Receives First Stem Cell Therapy Using Her Own Skin Cells A Japanese woman is the first to receive retinal cells made from her own skin cells

Researchers at the RIKEN Center for Developmental Biology in Japan surgically transplanted a sheet of retinal pigment cells into the eye of a 70-year old woman on Friday.

The cells are the first induced pluripotent stem cells, or iPS cells, given to a human patient. They were made by Masayo Takahashi, who grew them from the patients own skin cells, which were treated with four genetic factors to revert back to an embryonic-like state. Takahashi then soaked the cells with the appropriate growth factors and other compounds so they developed into retinal pigment cells.

The patient was losing her sight due to macular degeneration, because her retinal pigment endothelial cells were damaged by an overgrowth of blood vessels. Replacing them with a new population of cells can restore her sight.

MORE: Stem-Cell Research: The Quest Resumes

Stem cell scientists are starting to test their treatments in eye-related diseases, because parts of the eye are protected from the bodys immune system, which could recognize the introduced cells as foreign and destroy them. Thats not a problem with the iPS cells, since they are made from the patients own skin cells, but its an added safety net to ensure that the therapy is safe and hopefully effective.

Because iPS cells are genetically treated to erase their skin cell development and revert them back to an embryonic-like state when they can become any type of cell, there are still concerns about their safety when transplanted into patients. The U.S. Food and Drug Administration has not yet approved a trial involving iPS cells so far, only stem cells made from excess IVF embryos have been approved for treating macular degeneration. A 19-member committee of the Japanese ministry of health approved the experimental procedure four days ago, according to Nature, after Takahashi made her case, with the help of Dr. Shinya Yamanaka of Kyoto University, who shared the 2012 Nobel Prize for discovering iPS cells.

MORE: Stem Cell Miracle? New Therapies May Cure Chronic Conditions like Alzheimers

Japans stem cell scientists are hoping the surgery is a success; the field has been struggling since a well-publicized paper about a new way to make iPS cells was retracted amid allegations of fraud.

Its not known whether the cells will continue to grow and form abnormal tumors, or whether they will migrate to other parts of the body. But now that the first patient has received them, those questions and more, about the effectiveness of stem cell therapy might be answered soon.

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Woman Receives First Stem Cell Therapy Using Her Own Skin Cells

First iPS stem cell retina surgery gives hope for AMD patients

TOKYO - Japanese researchers Friday conducted the world's first surgery with "iPS" stem cells on serious eye disease Friday, possibly paving the way for treatment of a common cause of blindness, two institutions involved said.

A female patient with age-related macular degeneration (AMD), a common medical condition that can lead to blindness in older people, had a sheet of retina cells that had been created from iPS cells implanted.

The research team used induced Pluripotent Stem (iPS) cells -- which have the potential to develop into any cell in the body -- that had originally come from the skin of the patient, the institutions said in a statement.

Until the discovery of iPS several years ago, the only way to obtain stem cells was to harvest them from human embryos.

The surgery is still at an experimental stage, but if it is successful, doctors hope it will stop the deterioration in vision that comes with AMD.

The patient -- one of six expected to take part in the trial -- will be monitored over the next four years to determine how well the implants have performed, whether the body has accepted them and if they have become cancerous.

AMD, a condition that is incurable at present, affects mostly middle-aged and older people and can lead to blindness. It afflicts around 700,000 people in Japan alone.

The study was being carried out by researchers from government-backed research institution Riken and the Institute of Biomedical Research and Innovation Hospital.

Stem cell research is a pioneering field that has excited many in the scientific community with the potential they believe it offers.

Stem cells are infant cells that can develop into any part of the body.

See more here:
First iPS stem cell retina surgery gives hope for AMD patients

Stem cells help researchers understand how schizophrenic brains function

PUBLIC RELEASE DATE:

11-Sep-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press @CellPressNews

Using human induced pluripotent stem cells (hiPSCs), researchers have gained new insight into what may cause schizophrenia by revealing the altered patterns of neuronal signaling associated with this disease. They did so by exposing neurons derived from the hiPSCs of healthy individuals and of patients with schizophrenia to potassium chloride, which triggered these stem cells to release neurotransmitters, such as dopamine, that are crucial for brain function and are linked to various disorders. By discovering a simple method for stimulating hiPSCs to release neurotransmitters, the findings in the International Society for Stem Cell Research's journal Stem Cell Reports, published by Cell Press, could provide new insights into how neurons communicate with each other and could lead to a better understanding of the neural mechanisms underlying a range of brain disorders.

"This study is novel because it shows that stem cell neurons derived from patients can provide new insight into neurotransmitter mechanisms occurring in brain disorders such as schizophrenia," says senior study author Vivian Hook of the University of California, San Diego. "The approach of this study has broad opportunities for uncovering the neurochemistry of brain cell communication in numerous brain disorders, via these studies of human disease in a dish. Findings from these studies will lead to new therapeutic strategies for brain disorders, especially those mental and neurological diseases for which no drug treatments exist today."

hiPSCS are cells that are taken from adults, genetically reprogrammed to an embryonic stem cell-like state, and then converted into specialized cells such as neurons. Patient-derived hiPSCs offer the possibility of modeling an individual's disease in a dish and assessing which drugs will most effectively treat the disease. Because dysfunction in neural communication is linked to brain disorders such as schizophrenia, Hook and Fred Gage of The Salk Institute and Kristen Brennand of the Icahn School of Medicine at Mount Sinai set out to determine whether hiPSC-derived neurons can be induced to release important brain signaling chemicals, allowing disease mechanisms to be studied in a dish.

To address this question, the researchers exposed hiPSC-derived neurons from healthy individuals and patients with schizophrenia to a chemical known to stimulate the release of neurotransmitters. They found that these cells contained neurotransmitter-producing enzymes and were capable of secreting dopamine, norepinephrine, and epinephrineneurotransmitters that are crucial for brain function and that are linked to various disorders. Moreover, secretion of the three neurotransmitters was enhanced in hiPSC-derived neurons from schizophrenia patients compared with those from healthy individuals.

"The significance of this study is that patient-derived stem cell neurons can uncover previously unknown neurotransmitter brain mechanisms occurring in schizophrenia," Hook says. "Because in vivo human brain research is limited, hiPSC neurons derived from patients create new opportunities to understand changes occurring in brain cells occurring in nervous system disorders. These approaches can potentially define new drug targets for the development of therapeutic agents to improve the lives of schizophrenia patients."

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Stem Cell Reports, Hook et al.: "Human iPSC Neurons Display Activity-Dependent Neurotransmitter Secretion: Aberrant Catecholamine Levels in Schizophrenia Neurons."

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Stem cells help researchers understand how schizophrenic brains function