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Scientists generate a new type of human stem cell that has half a genome

  |   Stem Cells   |   No comment

Date: March 16, 2016

Source: Hebrew University of Jerusalem

 

Summary: Scientists have succeeded in generating a new type of embryonic stem cell that carries a single copy of the human genome, instead of the two copies typically found in normal stem cells. These are the first human cells that are known to be capable of cell division with just one copy of the parent cell’s genome. Since the stem cells were a genetic match to the egg cell donor, they could also be used to develop cell-based therapies for diseases such as blindness, diabetes, or other conditions in which genetically identical cells offer a therapeutic advantage. Because their genetic content is equivalent to germ cells, they might also be useful for reproductive purposes.

 

Scientists have succeeded in generating a new type of embryonic stem cell that carries a single copy of the human genome, instead of the two copies typically found in normal stem cells. These are the first human cells that are known to be capable of cell division with just one copy of the parent cell’s genome. The scientists, from The Hebrew University of Jerusalem, Columbia University Medical Center (CUMC) and The New York Stem Cell Foundation Research Institute (NYSCF), reported their findings in the journal Nature. Since the stem cells were a genetic match to the egg cell donor, they could also be used to develop cell-based therapies for diseases such as blindness, diabetes, or other conditions in which genetically identical cells offer a therapeutic advantage. Because their genetic content is equivalent to germ cells, they might also be useful for reproductive purposes.

 

Scientists from The Hebrew University of Jerusalem, Columbia University Medical Center (CUMC) and The New York Stem Cell Foundation Research Institute (NYSCF) have succeeded in generating a new type of embryonic stem cell that carries a single copy of the human genome, instead of the two copies typically found in normal stem cells. The scientists reported their findings today in the journal Nature.

 

The stem cells described in this paper are the first human cells that are known to be capable of cell division with just one copy of the parent cell’s genome.

 

Human cells are considered ‘diploid’ because they inherit two sets of chromosomes, 46 in total, 23 from the mother and 23 from the father. The only exceptions are reproductive (egg and sperm) cells, known as ‘haploid’ cells because they contain a single set of 23 chromosomes. These haploid cells cannot divide to make more eggs and sperm.

 

Previous efforts to generate embryonic stem cells using human egg cells had resulted in diploid stem cells. In this study, the scientists triggered unfertilized human egg cells into dividing. They then highlighted the DNA with a fluorescent dye and isolated the haploid stem cells, which were scattered among the more populous diploid cells.

 

The researchers showed that these haploid stem cells were pluripotent — meaning they were able to differentiate into many other cell types, including nerve, heart, and pancreatic cells — while retaining a single set of chromosomes.

 

“This study has given us a new type of human stem cell that will have an important impact on human genetic and medical research,” said Nissim Benvenisty, MD, PhD, Director of the Azrieli Center for Stem Cells and Genetic Research at the Hebrew University of Jerusalem and principal co-author of the study. “These cells will provide researchers with a novel tool for improving our understanding of human development, and the reasons why we reproduce sexually, instead of from a single parent.”

 

The researchers were also able to show that by virtue of having just a single copy of a gene to target, haploid human cells may constitute a powerful tool for genetic screens. Being able to affect single-copy genes in haploid human stem cells has the potential to facilitate genetic analysis in biomedical fields such as cancer research, precision and regenerative medicine.

 

“One of the greatest advantages of using haploid human cells is that it is much easier to edit their genes,” explained Ido Sagi, the PhD student who led the research at the Azrieli Center for Stem Cells and Genetic Research at the Hebrew University of Jerusalem. In diploid cells, detecting the biological effects of a single-copy mutation is difficult, because the other copy is normal and serves as “backup.”

 

Since the stem cells described in this study were a genetic match to the egg cell donor, they could also be used to develop cell-based therapies for diseases such as blindness, diabetes, or other conditions in which genetically identical cells offer a therapeutic advantage. Because their genetic content is equivalent to germ cells, they might also be useful for reproductive purposes.

 

The research, supported by The New York Stem Cell Foundation, the New York State Stem Cell Science Program, and by the Azrieli Foundation, underscores the importance of private philanthropy in advancing cutting-edge science.


Story Source:

The above post is reprinted from materials provided by Hebrew University of JerusalemNote: Materials may be edited for content and length.


Journal Reference:

  1. Ido Sagi, Gloryn Chia, Tamar Golan-Lev, Mordecai Peretz, Uri Weissbein, Lina Sui, Mark V. Sauer, Ofra Yanuka, Dieter Egli, Nissim Benvenisty. Derivation and differentiation of haploid human embryonic stem cellsNature, 2016; DOI: 10.1038/nature17408

 

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Unraveling the mystery of stem cells

  |   Stem Cells   |   No comment

Neuroscientists document some of the first steps in the process by which a stem cell transforms into different cell types

Date: March 24, 2016
Source: University of California – Santa Barbara
Summary: How do neurons become neurons? They all begin as stem cells, undifferentiated and with the potential to become any cell in the body. Now neuroscientists document some of the first steps in the process by which a stem cell transforms into different cell types.

How do neurons become neurons? They all begin as stem cells, undifferentiated and with the potential to become any cell in the body.

 

Until now, however, exactly how that happens has been somewhat of a scientific mystery. New research conducted by UC Santa Barbara neuroscientists has deciphered some of the earliest changes that occur before stems cells transform into neurons and other cell types.

 

Working with human embryonic stems cells in petri dishes, postdoctoral fellow Jiwon Jang discovered a new pathway that plays a key role in cell differentiation. The findings appear in the journal Cell.

 

“Jiwon’s discovery is very important because it gives us a fundamental understanding of the way stem cells work and the way they begin to undergo differentiation,” said senior author Kenneth S. Kosik, the Harriman Professor of Neuroscience Research in UCSB’s Department of Molecular, Cellular, and Developmental Biology. “It’s a very fundamental piece of knowledge that had been missing in the field.”

 

When stem cells begin to differentiate, they form precursors: neuroectoderms that have the potential to become brain cells, such as neurons; or mesendoderms, which ultimately become cells that comprise organs, muscles, blood and bone.

 

Jang discovered a number of steps along what he and Kosik labeled the PAN (Primary cilium, Autophagy Nrf2) axis. This newly identified pathway appears to determine a stem cell’s final form.

 

“The PAN axis is a very important player in cell fate decisions,” explained Jang. “G1 lengthening induces cilia protrusion and the longer those cellular antennae are exposed, the more signals they can pick up.”

 

For some time, scientists have known about Gap 1 (G1), the first of four phases in the cell cycle, but they weren’t clear about its role in stem cell differentiation. Jang’s research demonstrates that in stem cells destined to become neurons, the lengthening phase of G1 triggers other actions that cause stem cells to morph into neuroectoderms.

 

During this elongated G1 interval, cells develop primary cilia, antennalike protrusions capable of sensing their environment. The cilia activate the cells’ trash disposal system in a process known as autophagy.

 

Another important factor is Nrf2, which monitors cells for dangerous molecules such as free radicals — a particularly important job for healthy cell formation.

 

“Nrf2 is like a guardian to the cell and makes sure the cell is functioning properly,” said Kosik, co-director of the campus’s Neuroscience Research Institute. “Nrf2 levels are very high in stem cells because stem cells are the future. Without Nrf2 watching out for the integrity of the genome, future progeny are in trouble.”

 

Jang’s work showed that levels of Nrf2 begin to decline during the elongated G1 interval. This is significant, Kosik noted, because Nrf2 doesn’t usually diminish until the cell has already started to differentiate.

 

“We thought that, under the same conditions if the cells are identical, that both would differentiate the same way, but that is not what we found,” Jang said. “Cell fate is controlled by G1 lengthening, which extends cilia’s exposure to signals from their environment. That is one cool concept.”

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Stem cells used to identify cellular processes related to glaucoma

  |   Eye Disease   |   No comment

Date: March 21, 2016

Source: Indiana University-Purdue University Indianapolis School of Science

Summary: Using stem cells derived from human skin cells, researches have successfully demonstrated the ability to turn stem cells into retinal ganglion cells, the neurons that conduct visual information from the eye to the brain. Their goal is the development of therapies to prevent or cure glaucoma.

 

Using stem cells derived from human skin cells, researchers led by Jason Meyer, assistant professor of biology, along with graduate student Sarah Ohlemacher of the School of Science at Indiana University-Purdue University Indianapolis, have successfully demonstrated the ability to turn stem cells into retinal ganglion cells (RGCs), the neurons that conduct visual information from the eye to the brain. Their goal is the development of therapies to prevent or cure glaucoma.

 

In addition to glaucoma, a group of degenerative diseases that damage the eye’s optic nerve and can result in vision loss and blindness, this work has potential implications for treatment of optic- nerve injuries of the types incurred by soldiers in combat or athletes in contact sports.

 

In the study, which appears online in advance of publication in the journal Stem Cells, the IUPUI investigators took skin cells biopsied from volunteers with an inherited form of glaucoma and from volunteers without the disease and genetically reprogrammed them to become pluripotent stem cells, meaning they are able to differentiate into any cell type in the body. The researchers then directed the stem cells to become RGCs at which point the cells began adopting features specific to RGCs — features that were different in the cells of individuals with glaucoma than in the cells that came from healthy individuals.

 

Glaucoma is the most common disease that affects RGCs, which serve as the connection between the eye and the brain, sending information taken in by the eye to the brain for interpretation. When these cells are damaged or severed, the brain cannot receive critical information, leading to blindness. The National Institutes of Health’s National Eye Institute estimates that glaucoma affects more than 2.7 million people in the United States and more than 60 million worldwide.

 

“Skin cells from individuals with glaucoma are no different from skin cells of those without glaucoma,” said Meyer, a cell biologist and stem cell researcher, who also holds an appointment as a primary investigator with the Stark Neurosciences Research Institute at the Indiana University School of Medicine. “However, when we turned glaucoma patients’ skin cells into stem cells and then into RGCs, the cells became unhealthy and started dying off at a much faster rate than those of healthy individuals.

 

“Now that we have produced cells that develop features of glaucoma in culture dishes, we want to see if compounds we add to these RGCs can slow down the degeneration process or prevent these cells from dying off. We already have found candidates that look promising and are studying them. In the more distant future, we may be able to use healthy patient cells as substitute cells as we learn how to replace cells lost to the disease. It’s a significant challenge, but it’s the ultimate — and, we think, not unrealistic — long-range goal.”


Story Source:

The above post is reprinted from materials provided by Indiana University-Purdue University Indianapolis School of ScienceNote: Materials may be edited for content and length.

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Are stem-cell therapies for parkinson’s disease ready for clinical trials?

  |   Neurological Diesease   |   No comment

Date: March 29, 2016

Source: IOS

Press Summary: As stem cell-based therapies are moving rapidly towards clinical trials, treatments for Parkinson’s Disease (PD), an incurable condition, may be on the horizon. A recent announcement of a Phase I/IIa clinical trial involving transplantation of stem cells into the first human subjects has raised hope among patients and sparked discussions in the research community.

 

Science Daily

 

As stem cell-based therapies are moving rapidly towards clinical trials, treatments for Parkinson’s Disease (PD), an incurable condition, may be on the horizon. A recent announcement of a Phase I/IIa clinical trial involving transplantation of stem cells into the first human subjects has raised hope among patients and sparked discussions in the research community. In a commentary published in the Journal of Parkinson’s Disease, authors propose five key questions that should be addressed as this trial begins.

News of California-based biotechnology company, International Stem Cell Corporation’s (ISCO) clinical trial spread rapidly through online and print news and social media. Many PD patients and their families have questioned whether they should try to sign up for such a study. “As with many such exiting news items, however, one should also react with caution, especially since the outcome of this trial can affect the development of other stem cell programs moving towards clinical trials,” explained lead author Roger A. Barker, PhD, of the John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, UK.

 

In the wake of clinical trial announcements from ISCO it is timely to provide insights into how the opportunities provided to PD patients in this and similar trials should be evaluated. Without this, the patient community is left trying to interpret complex scientific issues on its own, and individual patients cannot make informed decisions on whether they should seek to participate in the planned trials or not.

 

The authors review the clinical transplantation trial in PD planned by ISCO this year in light of the criteria defined by the GForce-PD (www.gforce-pd.com). This global collaborative initiative aims to define criteria to gauge progress from experimental results towards clinical trials, while ensuring that all steps are conducted to the highest standard and that the trials are not initiated prematurely.

 

Before any stem-cell-based trial in PD is done, the authors call for discussion of these five key questions:

 

1. What is being transplanted, and what is the proposed mechanism of action?

2. What are the pre-clinical safety and efficacy data supporting the use of the proposed stem cell product?

3. Can arguments concerning ethics, risk mitigation, or trial logistics outweigh concerns regarding the expected efficacy of the cell and constitute a primary justification for choosing one cell type over another in a clinical trial?

4. What is being claimed regarding the potential therapeutic value of the stem cell-based therapy — better control of symptoms or a cure?

5. What is the regulatory oversight of the trial and is it guided by input from experts in the field?

 

In this commentary, the authors briefly review how cell-based therapies for PD have evolved and discuss some of the early results, as well as some of the ethical issues concerning fetal stem-cell use. They then elaborate on the five key questions and express some concern that there is missing or incomplete information available from ISCO. In particular, there are concerns that the particular cell types being transplanted may not function as desired, and that supporting safety and efficacy data have not been made public. The consortium also suggests that the length of follow-up in the proposed trial may not be sufficient.

 

While early claims suggesting the possibility of a “cure” had been made, ISCO has now taken a more measured position regarding potential benefits. Nevertheless, the authors caution that exaggerated claims are all too common, given the regulatory hurdles, commercial interests, and personal ambitions of the participants in early-stage clinical trials.

 

With the reality of the first human clinical trial in patients with PD upon us, co-author and Editor-in-Chief of the Journal of Parkinson’s Disease Patrik Brundin, MD, PhD, Director of the Center for Neurodegenerative Science at Van Andel Research Institute in Grand Rapids, MI, commented, “This is an exciting prospect but should only be undertaken when all the necessary pre-clinical data and regulatory approvals have been obtained and verified and the criteria for moving those cells to trials fully resolved and met. Acting prematurely has the potential not only to tarnish many years of scientific work, but can threaten to derail and damage this exciting field of regenerative medicine. Hopefully, in 2016, we are ready to take a more careful approach as we strive to repair the PD brain with stem cell-based therapies, avoiding many of the mistakes that have dogged this field over the last three decades.”

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Vision restored in rabbits following stem cell transplantation

  |   Eye Disease, Uncategorized   |   No comment

Date: March 9, 2016

Source: Cardiff University

Summary: Scientists have demonstrated a method for generating several key types of eye tissue from human stem cells in a way that mirrors whole eye development.

 

Scientists have demonstrated a method for generating several key types of eye tissue from human stem cells in a way that mirrors whole eye development.

When transplanted to an animal model of corneal blindness, these tissues are shown to repair the front of the eye and restore vision, which scientists say could pave the way for human clinical trials of anterior eye transplantation to restore lost or damaged vision.

 

A collaborative team comprising researchers from Cardiff University and Osaka University in Japan describe their findings today in Nature.

 

The eye is composed of highly specialized tissues that are derived from a variety of cell lineages during development.

 

Previous studies have demonstrated that particular cell types, such as those that constitute the retina or cornea, can be created in the laboratory from pluripotent stem cells. However, these studies do not represent the complexity of whole eye development.

 

This latest study reports the generation of multiple cell lineages of the eye, including the lens, cornea, and conjunctiva, using human induced pluripotent stem cells.

 

The scientists have been able to show that the corneal epithelial cells can be cultivated and transplanted onto the eyes of rabbits with experimentally induced blindness to surgically repair the front of the eye.

 

Study co-author Professor Andrew Quantock, from Cardiff University’s School of Optometry and Vision Sciences, said: “This research shows that various types of human stem cells are able to take on the characteristics of the cornea, lens and retina.

 

“Importantly, it demonstrates that one cell type — the corneal epithelium — could be further grown in the lab and then transplanted on to a rabbit’s eye where it was functional, achieving recovered vision.

 

“Our work not only holds potential for developing cells for treatment of other areas of the eye, but could set the stage for future human clinical trials of anterior eye transplantation to restore visual function.”

 

Around 4000 corneal grafts are performed by the NHS annually, which rely on human organ donation.

 

The research was funded by the Japanese government’s Agency for Medical Research and Development.

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ART AND MEDICINE at Williams Island

  |   ISCELLI NEWS   |   No comment

LEDISH MAGAZINE

I received an e-vite to see a really intriguing work of art.  Hans-Juergen R. Klemm owns a prestigious art gallery called CityLoftArt at 2200 Biscayne Blvd. in Miami.

 

He was the friend who sent me the invitation.  The one-night-only event was to take place in a lounge at Williams Island.  So far, par for the artistic course.  So off I went to enjoy what I thought would be a nice evening of art.  There was only one fascinating, kinetic work of art on view that evening, brought in by Hans and created by a French artist named Didier Legros. There were also some luxury accessories supplied by Neiman Marcus and a fashion show in the same space.  Libations were provided by PAMA Pomegranate Liqueur. Hans gave a short explanation about the dynamic art work that is presently (2/2016), on view in his gallery and then melted into the crowd of mostly women guests.

 

What most of us didn’t know was that there was going to be a presentation by Dr. Juan Castillo who is from Spain and presently works in South Florida and in Cancun, Mexico. The talk was about Stem Cell procedures. Dr. Castillo introduced himself as a part of the X ISCELL Integrative Stem Cell Institute. This is about the time when I looked around and noticed that most of the invited guests were not spring chickens, if you follow my drift.  The good doctor went on to explain the “potential of your own stem cells and peptides.”  Oh it was smooth…pun intended.  We were all a captive audience… on many levels.

 

We received an informative lesson about what stem cell research and applications really is and what it can do.

 

“Stem cells represent the most basic natural material that your body needs to heal.  Stem cells are “unspecialized” cells.  They are “blanks” capable of developing into another type of cell, divide into multiple and identical daughter cells, and renewal through cell division giving rise to daughter cells and at the same time maintaining its unspecialized or generic state.  Stem cells grow, repair and regenerate new cells needed to regenerate or replace damaged tissue.”

 

I have to tell you I was mesmerized and I venture to write that I believe many of the other guests were too.  Parts of the body can be improved with the inclusion of stem cells.  But here’s what really got to me.  Stem cells may very well be able to help Alzheimer victims. I’ve had several parents who were affected by Alzheimer’s Disease so I’m passionate about the subject.  With a huge percentage of the population getting older and more susceptible to ‘old age problems’ something like stem cell therapy might finally be the solution so many people have been waiting for.  If you’re interested in knowing more, visit www.iscelli.com.  I’m going to study up on the subject.  I’ll keep you posted.

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