A protein required for integrity of induced pluripotent stem cells

Cell reprogramming converts specialised cells such as nerve cells or skin cells towards an embryonic stem cell state. This reversal in the evolutionary development of cells also requires a reversal in the biology of telomeres, the structures that protect the ends of chromosomes; whilst under normal conditions telomeres shorten over time, during cell reprogramming they follow the opposite strategy and increase in length.

A study published today in the journal Stem Cell Reports, from the Cell Publishing Group, reveals that the SIRT1 protein is needed to lengthen and maintain telomeres during cell reprogramming. SIRT1 also guarantees the integrity of the genome of stem cells that come out of the cell reprogramming process; these cells are known as iPS cells (induced Pluripotent Stem cells).

The study has been carried out by the Spanish National Cancer Research Centre's Telomeres and Telomerase Group, in collaboration with the CNIO's Transgenic Mice Core Unit.

Since the Japanese scientist Shinya Yamanaka first obtained iPS cells from adult tissue in 2006, regenerative medicine has become one of the most exciting and rapidly developing fields in biomedicine. There is a very ambitious aim, given the ability to differentiate iPS cells into any type of cell; this would allow for the regeneration of organs damaged by diseases such as Alzheimer, diabetes or cardiovascular diseases.

The nature of iPS cells however is causing intense debate. The latest research shows that chromosome aberrations and DNA damage can accumulate in these cells. "The problem is that we don't know if these cells are really safe," says Mara Luigia De Bonis, a postdoctoral researcher of the Telomeres and Telomerase Group who has done a large part of the work.

In 2009, the same CNIO laboratory discovered that telomeres increase in length during cell reprogramming (Marion et al., Cell Stem Cell, 2009); this increase is important as it allows stem cells to acquire the immortality that characterises them.

One year later, it was demonstrated that the levels of SIRT1 -- a protein belonging to the sirtuin family and that is involved in the maintenance of telomeres, genomic stability and DNA damage response -- are increased in embryonic stem cells. The question CNIO researchers asked was: is SIRT1 involved in cell reprogramming?

SAFER STEM CELLS

Employing mouse models and cell cultures as research tools in which SIRT1 had been removed, the team has discovered that this protein is necessary for reprogramming to occur correctly and safely."We observed cell reprogramming in the absence of SIRT1, but over time the produced iPS cells lengthen telomeres less efficiently and suffer from chromosome aberrations and DNA damage," says De Bonis. "SIRT1 helps iPS cells to remain healthy," she concludes.

The authors describe how this protective effect on iPS cells is, in part, mediated by the cMYC regulator. SIRT1 slows the degradationof cMYC, which results in an increase in telomerase (the enzyme that increases telomere length) in cells.

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A protein required for integrity of induced pluripotent stem cells

Human Stem Cells Converted to Functional Lung Cells …

NEW YORK, NY For the first time, scientists have succeeded in transforming human stem cells into functional lung and airway cells. The advance, reported by Columbia University Medical Center (CUMC) researchers, has significant potential for modeling lung disease, screening drugs, studying human lung development, and, ultimately, generating lung tissue for transplantation. The study was published today in the journal Nature Biotechnology.

Human embryonic stem cells differentiated into type II alveolar lung epithelial cells (green). A large portion of these transformed cells express surfactant protein B (red), which indicates that they are functional type II cells. Image credit: Sarah Xuelian Huang, PhD at the Columbia Center for Translational Immunology at CUMC.

Researchers have had relative success in turning human stem cells into heart cells, pancreatic beta cells, intestinal cells, liver cells, and nerve cells, raising all sorts of possibilities for regenerative medicine, said study leader Hans-Willem Snoeck, MD, PhD, professor of medicine (in microbiology & immunology) and affiliated with the Columbia Center for Translational Immunology and the Columbia Stem Cell Initiative. Now, we are finally able to make lung and airway cells. This is important because lung transplants have a particularly poor prognosis. Although any clinical application is still many years away, we can begin thinking about making autologous lung transplantsthat is, transplants that use a patients own skin cells to generate functional lung tissue.

The research builds on Dr. Snoecks 2011 discovery of a set of chemical factors that can turn human embryonic stem (ES) cells or human induced pluripotent stem (iPS) cells into anterior foregut endodermprecursors of lung and airway cells. (Human iPS cells closely resemble human ES cells but are generated from skin cells, by coaxing them into taking a developmental step backwards. Human iPS cells can then be stimulated to differentiate into specialized cellsoffering researchers an alternative to human ES cells.)

In the current study, Dr. Snoeck and his colleagues found new factors that can complete the transformation of human ES or iPS cells into functional lung epithelial cells (cells that cover the lung surface). The resultant cells were found to express markers of at least six types of lung and airway epithelial cells, particularly markers of type 2 alveolar epithelial cells. Type 2 cells are important because they produce surfactant, a substance critical to maintain the lung alveoli, where gas exchange takes place; they also participate in repair of the lung after injury and damage.

The findings have implications for the study of a number of lung diseases, including idiopathic pulmonary fibrosis (IPF), in which type 2 alveolar epithelial cells are thought to play a central role. No one knows what causes the disease, and theres no way to treat it, says Dr. Snoeck. Using this technology, researchers will finally be able to create laboratory models of IPF, study the disease at the molecular level, and screen drugs for possible treatments or cures.

In the longer term, we hope to use this technology to make an autologous lung graft, Dr. Snoeck said. This would entail taking a lung from a donor; removing all the lung cells, leaving only the lung scaffold; and seeding the scaffold with new lung cells derived from the patient. In this way, rejection problems could be avoided. Dr. Snoeck is investigating this approach in collaboration with researchers in the Columbia University Department of Biomedical Engineering.

I am excited about thiscollaboration with Hans Snoeck, integrating stem cell science withbioengineering in the search for new treatments for lung disease, said Gordana Vunjak-Novakovic, PhD, co-author of the paper and Mikati Foundation Professor of Biomedical Engineering at Columbias Engineering School and professor of medical sciences at Columbia University College of Physicians and Surgeons.

The paper is titled, Highly efficient generation of airway and lung epithelial cells from human pluripotent stem cells.

The other contributors are Sarah X.L. Huang, Mohammad Naimul Islam, John ONeill, Zheng Hu, Yong-Guang Yang, Ya-Wen Chen, Melanie Mumau, Michael D. Green, and Jahar Bhattacharya (all at CUMC).

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Cloning advance means human tissues could be regrown, even in old age

The advance could lead to tissue-transplant operations for a range of debilitating disorders, such as Parkinson's disease, multiple sclerosis, heart disease and spinal cord injuries.

Last year, a team created stem cells from the skin cells of babies, but it was unclear whether it would work in adults.

However, a team of scientists from the Research Institute for Stem Cell Research at CHA Health Systems in Los Angeles and the University of Seoul said they had achieved the same result with two men, one aged 35, the other the 75-year-old. "The proportion of diseases you can treat with lab-made tissue increases with age. So if you can't do this with adult cells it is of limited value," said Robert Lanza, co-author of the research, which was published in the journal Cell Stem Cell.

The technique works by removing the nucleus from an unfertilised egg and replacing it with the nucleus of a skin cell. An electric shock causes the cells to divide until they form a "blastocyst", a small ball of a few hundred cells.

In IVF, a blastocyst is implanted into the womb, but with the new technique the cells would be harvested to create other organs or tissues.

The breakthrough is likely to reignite the debate about the ethics of creating human embryos for medical purposes and the possible use of the same technique to produce cloned babies - which is illegal in Britain.

Although the embryos created may not produce a human clone even if implanted in a womb, the prospect is now closer. However, scientists have tried for years to clone monkeys and have yet to succeed.

Dr Lanza admitted that without strong regulations, the early embryos produced in therapeutic cloning "could also be used for human reproductive cloning, although this would be unsafe and grossly unethical". However, he said it was important for the future of regenerative medicine that research into therapeutic cloning should continue.

Shoukhrat Mitalipov, a reproductive biologist from Oregon Health and Science University, who developed the technique last year, said: "The advance here is showing that [nuclear transfer] looks like it will work with people of all ages.

"I'm happy to hear that our experiment was verified and shown to be genuine."

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Cloning advance means human tissues could be regrown, even in old age

Single Cell Type Found To Cause Most Invasive Bladder Cancers: Study

Lawrence LeBlond for redOrbit.com Your Universe Online

Invasive bladder cancer (IBC), a malignant disease that currently affects more than 375,000 people worldwide, has been found to be caused by a single type of cell in the lining of the bladder, according to researchers with the Stanford University School of Medicine.

The researchers say this is the first study to pinpoint the normal cell type that can give rise to IBC. It is also the first study to show that most bladder cancers and their precancerous lesions arise from just one cell, which could also explain why many bladder cancers recur after therapy.

Weve learned that, at an intermediate stage during cancer progression, a single cancer stem cell and its progeny can quickly and completely replace the entire bladder lining, Philip Beachy, PhD, professor of biochemistry and of developmental biology, said in a statement. All of these cells have already taken several steps along the path to becoming an aggressive tumor. Thus, even when invasive carcinomas are successfully removed through surgery, this corrupted lining remains in place and has a high probability of progression.

Beachy and colleagues found that while cancer stem cells and the precancerous lesions they form express an important signaling protein known as sonic hedgehog, the cells of subsequent invasive cancers invariably do not a critical switch that appears vital for invasion and metastasis. This switch may explain certain confusing aspects of previous studies on the cellular origins of bladder cancer in humans. It also pinpoints a possible weak link in cancer progression that could be targeted by therapies.

This could be a game changer in terms of therapeutic and diagnostic approaches, said Michael Hsieh, MD, PhD, assistant professor of urology and a co-author of the study. Until now, its not been clear whether bladder cancers arise as the result of cancerous mutations in many cells in the bladder lining as the result of ongoing exposure to toxins excreted in the urine, or if its due instead to a defect in one cell or cell type. If we can better understand how bladder cancers begin and progress, we may be able to target the cancer stem cell, or to find molecular markers to enable earlier diagnosis and disease monitoring.

Bladder cancer is the fourth most common cancer in men and the ninth in women. There are two main types of bladder cancer: one that invades the muscle around the bladder and then metastasizes to other organs, and another that remains confined to the bladder lining. Unlike noninvasive cancers, most invasive bladder cancers are untreatable. Those that can be treated are expensive and difficult to cure, and with a high likelihood of recurrences, ongoing monitoring is required.

To determine what genes or cell types are at play in the formation of bladder cancer, the study team used a mouse model that closely mimicked what happens in humans. Usually, researchers rely on prior knowledge or guesses as to what genes are involved and often genetically alter cell types in animals to induce overexpression of a gene known to be involved in tumorigenesis or to block the expression of a gene that inhibits cancer development.

LINK TO SMOKING

Previous work by Beachy and his colleagues suggested that basal cells play a role in bladder cancer. However, the new study offered an unbiased approach.

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Single Cell Type Found To Cause Most Invasive Bladder Cancers: Study

World Stem Cells,LLC | Stem Cell Treatments & Stem Cell …

Who We Are at World Stem Cells, LLC

Advanced stem cell treatments offered by Would Stem Cells, LLC a patient management company for qualified patients at the medical facilities World Stem Cells Clinic, http://worldstemcells.com/clinic-team.html in Cancun provides an opportunity for a better quality of life. The clinic and laboratory were designed, built and are operated under the stringent guidelines as established by The International Cellular Medical Society (ICMS) and the US Federal Drug Administrations Good Tissue Practice (cGTP)regulations for pharmaceutical, biologics and clinical laboratories. The strict adherence to these established guidelines and policies guarantees the highest quality of clinical care and stem cell treatment safety for you.

What Is Done

World Stem Cells Clinics medical staff and clinical physicians will examine you and review all available medical records, radiology films, CT scans and other diagnostic information to assess if stem cell therapy will be a helpful primary treatment or adjunctive therapy for your specific condition.

Then, the medical doctors meet and confer with the research scientists for a pre-treatment planning meeting. This Stem cell treatment planning conference takes advantage of decades of the staffs clinical experience, your current condition, your available social support system, full review of your medical history as well as an inclusion and consideration of any recently published research literature on stem cell treatments. In other words, you are provided a detailed, systematic and entirely unique treatment care plan for his or her needs.

Creating the best treatment

Sorry, they do not perform a one or two day treatment as it would not be medically sound and could not provide the benefits or safety that the World Stem Cells Clinic treatment schedule gives (please do not be fooled). Your Stem Cell Treatment at World Stem Cells Clinic takes 5 days to complete as the treatments are comprehensive and designed to maximize the benefits and safety you derive from the process.

How Is It Done

The World Stem Cells Clinics team harvest autologous stem cells from your own bone marrow, adipose (fat) tissue or circulating stem cells, within your bloodstream. They also offer allogeneic stem cells from other donors. These cells are harvested in the same way and under the same conditions. They are simply obtained from a donor as opposed to from you. They do not utilize fetal or laboratory-cultured embryonic stem cells. They chose not to use these sources of stem cells to prevent potential complications from contamination or side effects and adverse events such as graft versus host disease (GVHD).

After collection, your stem cells are tested and processed at the state-of-the-art and Good Tissue Practice (cGTP) laboratories. Data regarding the source of your stem cells, the amount harvested, and other information is recorded to ensure proper transfusion of your own cell or those of a chosen donor.

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World Stem Cells,LLC | Stem Cell Treatments & Stem Cell ...

Stem Cell Therapy for Arthritis and Injuries | Regenexx …

Welcome to Regenexx Stem Cell Procedures for Arthritis & Injuries Chris Centeno 2009-09-30T12:05:38+00:00 The Regenexx Procedures are a family of non-surgical stem cell and blood platelet treatments for common injuries and degenerative joint conditions, such as osteoarthritis and avascular necrosis. These stem cell procedures utilize a patients own stem cells or blood platelets to help heal damaged tissues, tendons, ligaments, cartilage, spinal disc, or bone. Regenexx Stem Cell and Blood Platelet Procedures offer a viable alternative for individuals suffering from joint pain, or who may be considering elective surgery or joint replacement due to injury or arthritis. Patients avoid the lengthy periods of downtime, and painful rehabilitation that typically follow invasive surgeries. Commonly Treated Conditions - Regenexx Stem Cell and Platelet Procedures

The list below represents the most commonly treated conditions using Regenexx stem cell or platelet procedures. It is not a complete list, so please contact us or complete the Regenexx Candidate Form if you have questions about whether you or your condition can be treated with these non-surgical procedures. The type of procedure used (stem cell or blood platelet) to treat these conditions is largely dependent upon the severity of the injury or condition.

The Centeno-Schultz Clinic is theoriginalstem cell based musculoskeletal practice in the U.S., with more stem cell orthopedics experience than any other clinic. We are also physician leaders in stem cell treatments for arthritis and injuries in terms of research presentations, publications, and academic achievements.

The episode features Dr. Centeno and Dr. Hanson, along with patient Barbee James, who required stem cell treatment after a failed micro fracture and continued problems following traditional knee surgery. The episode provided a nice overview of a Regenexx-SD (same-day) stem cell procedure for Barbees knee cartilage damage.

On February 28, 2013 Seattle King TV featured Regenexx patient Paul Lyon, who underwent a Regenexx-SD knee procedure in our Broomfield clinic. The story looks at his results and includes an interview with Dr. Christopher Centeno, along with footage in our advanced lab where stem cells are processed as part of the procedure.

Regenexx Network Physician Dr. Mayo Friedlis (Washington D.C. area) is featured in this recent news story about stem cell therapy, which explores the Regenexx-SD stem cell procedure and a very active seniors outcome following his knee stem cell injection.

Our Pittsburgh, PA. Regenexx Network Provider, Rehabilitation and Pain Specialists, was recently featured in a news story about treating a patients knee pain with stem cells. The patient returned to their clinic for this procedure after experiencing success with the stem cell treatment he received on his other knee.

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Stem Cell Therapy for Arthritis and Injuries | Regenexx ...

Stem-cell research shows promise in restoring sight

Stem-cell research has always been looked at as either a path towards human cloning or a way to potentially re-create human tissue and now it appears the latter is finally starting to see some progress.

Researchers, according to The Washington Post, have found a way to make adult stem-cells grow into tissue with some urging by scientists.

This means that people suffering from diabetes could possibly have insulin-producing cells, made by scientists. People with macular degeneration would never go blind and entire organs could possibly be matched to patients in order to replace diseased ones.

According to Nature World News, the research is approaching human trials as far as treating blindness with stem-cells.

So far the results have been extremely encouraging. One patient, who had been judged legally blind, gained full eyesight again.

This is done with three drops of retinal pigment epithelium cells underneath the retina, which is detached for the procedure.

Though stem-cell research controversy seemed to be so last decade as people worried about cloning, scientists are certainly stirring up some controversy with new treatment, but may also change many lives.

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Stem-cell research shows promise in restoring sight

Stem-cell Research and the Catholic Church

ORLANDO, Fla. (CNS) Declaring that stem-cell research does not present a conflict between science and religion, the U.S. bishops overwhelmingly approved a statement June 13 calling the use of human embryos in such research "gravely immoral" and unnecessary.

In the last vote of the public session of their June 12-14 spring general assembly in Orlando, the bishops voted 191-1 in favor of the document titled "On Embryonic Stem-Cell Research: A Statement of the U.S. Conference of Catholic Bishops."

"It now seems undeniable that once we cross the fundamental moral line that prevents us from treating any fellow human being as a mere object of research, there is no stopping point," the document said. "The only moral stance that affirms the human dignity of all of us is to reject the first step down this path."

Archbishop Joseph F. Naumann of Kansas City, Kan., introduced the document on behalf of Philadelphia Cardinal Justin Rigali, chairman of the bishops' Committee on Pro-Life Activities, who was not at the Orlando meeting.

Consideration of the stem-cell document came after an intense and complicated debate at the meeting over a 700-page liturgical translation. Archbishop Naumann thanked those involved in the liturgical debate for "making stem-cell research seem simple," which drew laughs from the other bishops.

The seven-page policy statement was approved with little debate and few amendments.

Archbishop Naumann said it would be issued in an "attractive educational brochure" intended for the "broadest possible distribution."

Also coming out this summer, he said, are three educational resources on the medical advances being made with adult stem cells: a 16-minute DVD called "Stem-Cell Research: Finding Cures We Can All Live With"; an updated parish bulletin insert on the topic; and a brochure on "Stem Cells and Hope for Patients," which will be part of the bishops' annual Respect Life observance.

Although the U.S. bishops have been active in the national debate on stem cells, individually and collectively, this marks the first time they have addressed the issue in a document "devoted exclusively" to that topic, Archbishop Naumann said.

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Stem-cell Research and the Catholic Church

What Is Stem Cell Research? (with pictures)

anon357394 Post 155

Obviously, some of you dont have kids. The life of a child is worth so much more than any adult. You got to live. What if that embryo happened to be you? Would you then feel that it is OK to conduct this research?

I am a mother of two, soon to be three. I don't care about any of that just long as my kids at least get a chance at living and there is a God. I had a 50 percent chance of having babies because of a huge benign tumor that grew on my left ovary and killed my left fallopian tube.

I prayed for my babies and got them every time. Besides that, everybody has their beliefs. My thing is your children. Would you put them through this? My mom had a number of health issues. She died after I had my daughter. I would have given anything to keep her alive, but not my baby. I understand it could save lives, but you cannot stop the inevitable science or not. It has been proven that if it is meant to be, it will. I am also researching for a school project and I am a little more against it than for it. I would much prefer the umbilical research, then the embryo research. I know the parent of the child has donated it, but don't you think in some way that this person could be desperate or misled in a way and doesn't know where to turn?

I watched this gruesome abortion video and the lady was 12 weeks along. You could see the child trying to fight for its life. Murder is murder. Helping to save other people or not -- that's like you seeing a man trying to rape a woman and you shoot him dead. It's the same if you were trying to save her life but you get persecuted and convicted for taking matters into your own hands. I am sorry for those people who are sick and have sick babies. I know what it is like to lose loved ones over untreatable diseases. Im against embryo research and I'm not thinking about me. It is about a baby. Sure, it isnt completely formed, but it's still a child, or at least will grow into one, I wish harm on nobody. There is no harm meant and Im not trying to make someone mad. Im just trying to throw some new views into the situation.

Stem cell research can only benefit society and advance us as a species. If your argument is religious, the you are not thinking. You are letting your emotions and beliefs speak for you, not your logic or common sense. A bunch of cells is not a baby, and helping the living is not against "God's will". This is a good thing and it will continue regardless of religious views, because it makes sense.

I'm still kind of learning about this topic, but abortion is something I feel strongly against, but if a baby was taken from it's mother with the mother's okay and they were trying to save people's lives, I would be completely okay with that.

I believe that God does not exist, and that stem cell research is truly phenomenal. This research should not be controversial, nor should it be banned; it is helping the living.

Most of the people who say that stem cell research is bad are religious, but people living in the real world and believe in this thing called 'science' actually make a difference. Religion has only held back society and science. I wonder how many religious people would get angry if they knew that I was a homosexual, atheist physicist who believes in evolution and the big bang theory.

I am writing a persuasive essay on whether stem cell research should be legal or not (even though it already is in the U.S.). I was never a really religious person and stuck mainly to things that I knew for sure were happening. The thing is, most of the stem cells they are using for research are going to be discarded anyway. No one is claiming them, no one is caring about them, and they are just going to be thrown away. It is better for them to be used for a greater cause than just being thrown away and losing the chance to create treatments and cures for cancer and neurodegenerative diseases.

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What Is Stem Cell Research? (with pictures)

Center for Joint Regeneration Now Offering Several Stem Cell Procedures for Patients to Avoid Knee Replacement

Phoenix, Arizona (PRWEB) April 21, 2014

The Center for Joint Regeneration is now offering several stem cell procedures for patients with knee arthritis to help avoid the need for joint replacement. The procedures are offered by Board-certified and Fellowship-trained orthopedic doctors, with the stem cells being derived from either bone marrow or amniotic fluid. For more information and scheduling with the top stem cell providers in the greater Phoenix area, call (480) 466-0980.

For the hundreds of thousands of individuals who undergo a knee replacement every year, it should be considered an absolute last resort, after other conservative options have failed. Although the vast majority of knee replacements do well, the implants are not meant to last forever, the surgery does have potential risks and the biomechanics of the knee are significantly changed with the prosthetic implants.

Stem cells for knee arthritis have the potential to repair and regenerate damage from arthritis and relieve pain substantially. Center for Joint Regeneration offers these outpatient procedures with several methods.

The first involves usage of the patient's own bone marrow, with a short harvesting procedure, processing the bone marrow, and injection at the same setting into one or both knees.

Another method is with amniotic derived stem cell rich material, which not only possesses concentrated stem cells but also a significant amount of growth factors and hyaluronic acid. The material is a meteorologically privileged and has been used tens of thousands of times around the world with minimal adverse events.

Platelet rich plasma therapy for knee degeneration is also offered. PRP therapy has been shown in recent studies at Hospital for Special Surgery to work well for pain relief from knee arthritis. It also offers the ability to preserve knee cartilage based on serial MRI's performed in the study.

So far, clinical outcomes with the stem cell regenerative procedures have been excellent. The Board-Certified orthopedic doctors at Center for Joint Regeneration, Doctors Farber and Dewanjee, are exceptionally well trained and highly skilled at these outpatient procedures.

For those individuals looking to avoid or delay the need for knee replacement due to degenerative arthritis, call the Center for Joint Regeneration today at (480) 466-0980. The Center offers stem cell treatments Phoenix and Scottsdale trust!

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Center for Joint Regeneration Now Offering Several Stem Cell Procedures for Patients to Avoid Knee Replacement