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Posts tagged with "stem cells"

Jun 1

Down syndrome neurons grown from stem cells show signature problems

neurosciencestuff:

Down syndrome, the most common genetic form of intellectual disability, results from an extra copy of one chromosome. Although people with Down syndrome experience intellectual difficulties and other problems, scientists have had trouble identifying why that extra chromosome causes such widespread effects.

In new research published this week, Anita Bhattacharyya, a neuroscientist at the Waisman Center at UW-Madison, reports on brain cells that were grown from skin cells of individuals with Down syndrome.

“Even though Down syndrome is very common, it’s surprising how little we know about what goes wrong in the brain,” says Bhattacharyya. “These new cells provide a way to look at early brain development.”

The study began when those skin cells were transformed into induced pluripotent stem cells, which can be grown into any type of specialized cell. Bhattacharyya’s lab, working with Su-Chun Zhang and Jason Weick, then grew those stem cells into brain cells that could be studied in the lab.

One significant finding was a reduction in connections among the neurons, Bhattacharyya says. “They communicate less, are quieter. This is new, but it fits with what little we know about the Down syndrome brain.”  Brain cells communicate through connections called synapses, and the Down neurons had only about 60 percent of the usual number of synapses and synaptic activity. “This is enough to make a difference,” says Bhattacharyya. “Even if they recovered these synapses later on, you have missed this critical window of time during early development.”

The researchers looked at genes that were affected in the Down syndrome stem cells and neurons, and found that genes on the extra chromosome were increased 150 percent, consistent with the contribution of the extra chromosome.

However, the output of about 1,500 genes elsewhere in the genome was strongly affected. “It’s not surprising to see changes, but the genes that changed were surprising,” says Bhattacharyya. The predominant increase was seen in genes that respond to oxidative stress, which occurs when molecular fragments called free radicals damage a wide variety of tissues.

“We definitely found a high level of oxidative stress in the Down syndrome neurons,” says Bhattacharyya. “This has been suggested before from other studies, but we were pleased to find more evidence for that. We now have a system we can manipulate to study the effects of oxidative stress and possibly prevent them.”

Down syndrome includes a range of symptoms that could result from oxidative stress, Bhattacharyya says, including accelerated aging. “In  their 40s, Down syndrome individuals age very quickly. They suddenly get gray hair; their skin wrinkles, there is rapid aging in many organs, and a quick appearance of Alzheimer’s disease. Many of these processes may be due to increased oxidative stress, but it remains to be directly tested.”

Oxidative stress could be especially significant, because it appears right from the start in the stem cells. “This suggests that these cells go through their whole life with oxidative stress,” Bhattacharyya adds, “and that might contribute to the death of neurons later on, or increase susceptibility to Alzheimer’s.”

Other researchers have created neurons with Down syndrome from induced pluripotent stem cells, Bhattacharyya notes. “However, we are the first to report this synaptic deficit, and to report the effects on genes on other chromosomes in neurons. We are also the first to use stem cells from the same person that either had or lacked the extra chromosome. This allowed us to look at the difference just caused by extra chromosome, not due to the genetic difference among people.”

The research, published the week of May 27 in the Proceedings of the National Academy of Sciences, was a basic exploration of the roots of Down syndrome. Bhattacharyya says that while she did not intend to explore treatments in the short term, “we could potentially use these cells to test or intelligently design drugs to target symptoms of Down syndrome.”

Stroke patients improve in first stem cell trial.

livasperiklis:

Divide and define: Clues to understanding how stem cells produce different kinds of cells

The apical tip of fruitfly testis containing germline stem cells and differentiating germ cells.…

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livasperiklis:

Divide and define: Clues to understanding how stem cells produce different kinds of cells

The apical tip of fruitfly testis containing germline stem cells and differentiating germ cells.…

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Apr 7
post-mitotic:

spherical cluster (neurosphere) of neurons with radiating beams of blinding neon light, differentiated from embryonic stem cells
(for the record, those are just cellular processes branching out from individual cells)
confocal (40x)
credit: Sharona Even-Ram

post-mitotic:

spherical cluster (neurosphere) of neurons with radiating beams of blinding neon light, differentiated from embryonic stem cells

(for the record, those are just cellular processes branching out from individual cells)

confocal (40x)

credit: Sharona Even-Ram

neurosciencestuff:

Leprosy Bacteria Turn Nerve System Cells into Stem Cells
The study, carried out in mice, found that in the early stages of infection, M. leprae were able to protect themselves from the body’s immune system by hiding in the Schwann cells. Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells.
Like typical stem cells, these cells were pluripotent, meaning they could then become other cell types, for instance muscle cells. This enabled M. leprae to spread to tissues in the body.
The study, published in the journal Cell, also shows that the bacteria-generated stem cells have unexpected characteristic. They can secrete specialized proteins – called chemokines – that attract immune cells, which in turn pick up the bacteria and spread the infection.
“We have found a new weapon in a bacteria’s armory that enables them to spread effectively in the body by converting infected cells to stem cells. Greater understanding of how this occurs could help research to diagnose bacterial infectious diseases, such as leprosy, much earlier,” said study lead author Prof Anura Rambukkana, Medical Research Council Center for Regenerative Medicine at the University of Edinburgh.
“This is very intriguing as it is the first time that we have seen that functional adult tissue cells can be reprogrammed into stem cells by natural bacterial infection, which also does not carry the risk of creating tumorous cells. Potentially you could use the bacteria to change the flexibility of cells, turning them into stem cells and then use the standard antibiotics to kill the bacteria completely so that the cells could then be transplanted safely to tissue that has been damaged by degenerative disease.”
Dr Rob Buckle, Head of Regenerative Medicine at the Medical Research Council Center for Regenerative Medicine at the University of Edinburgh, said: “this ground-breaking new research shows that bacteria are able to sneak under the radar of the immune system by hijacking a naturally occurring mechanism to ‘reprogramme’ cells to make them look and behave like stem cells. This discovery is important not just for our understanding and treatment of bacterial disease, but for the rapidly progressing field of regenerative medicine. In future, this knowledge may help scientists to improve the safety and utility of lab-produced pluripotent stem cells and help drive the development of new regenerative therapies for a range of human diseases, which are currently impossible to treat.”
The scientists believe mechanisms used by leprosy bacteria could exist in other infectious diseases. Knowledge of this newly discovered tactic used by bacteria to spread infection could help research to improve treatments and earlier diagnosis of infectious diseases.

neurosciencestuff:

Leprosy Bacteria Turn Nerve System Cells into Stem Cells

The study, carried out in mice, found that in the early stages of infection, M. leprae were able to protect themselves from the body’s immune system by hiding in the Schwann cells. Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells.

Like typical stem cells, these cells were pluripotent, meaning they could then become other cell types, for instance muscle cells. This enabled M. leprae to spread to tissues in the body.

The study, published in the journal Cell, also shows that the bacteria-generated stem cells have unexpected characteristic. They can secrete specialized proteins – called chemokines – that attract immune cells, which in turn pick up the bacteria and spread the infection.

“We have found a new weapon in a bacteria’s armory that enables them to spread effectively in the body by converting infected cells to stem cells. Greater understanding of how this occurs could help research to diagnose bacterial infectious diseases, such as leprosy, much earlier,” said study lead author Prof Anura Rambukkana, Medical Research Council Center for Regenerative Medicine at the University of Edinburgh.

“This is very intriguing as it is the first time that we have seen that functional adult tissue cells can be reprogrammed into stem cells by natural bacterial infection, which also does not carry the risk of creating tumorous cells. Potentially you could use the bacteria to change the flexibility of cells, turning them into stem cells and then use the standard antibiotics to kill the bacteria completely so that the cells could then be transplanted safely to tissue that has been damaged by degenerative disease.”

Dr Rob Buckle, Head of Regenerative Medicine at the Medical Research Council Center for Regenerative Medicine at the University of Edinburgh, said: “this ground-breaking new research shows that bacteria are able to sneak under the radar of the immune system by hijacking a naturally occurring mechanism to ‘reprogramme’ cells to make them look and behave like stem cells. This discovery is important not just for our understanding and treatment of bacterial disease, but for the rapidly progressing field of regenerative medicine. In future, this knowledge may help scientists to improve the safety and utility of lab-produced pluripotent stem cells and help drive the development of new regenerative therapies for a range of human diseases, which are currently impossible to treat.”

The scientists believe mechanisms used by leprosy bacteria could exist in other infectious diseases. Knowledge of this newly discovered tactic used by bacteria to spread infection could help research to improve treatments and earlier diagnosis of infectious diseases.

Jan 8
biocanvas:

A magnified view of human embryonic stem cells.
Image by Melanie Ivancic, Joseph Klim, and Laura Kiessling, University of Wisconsin-Madison.

biocanvas:

A magnified view of human embryonic stem cells.

Image by Melanie Ivancic, Joseph Klim, and Laura Kiessling, University of Wisconsin-Madison.

neurosciencestuff:

Human Induced Pluripotent Stem Cell-Derived Models to Investigate Human Cytomegalovirus Infection in Neural Cells
Human cytomegalovirus (HCMV) infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS) cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs), neural progenitor cells (NPCs) and neurons suggests that (i) iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii) Neural stem cells have impaired differentiation when infected by HCMV; (iii) NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv) most iPS-derived neurons are not permissive to HCMV infection; and (v) infected neurons have impaired calcium influx in response to glutamate.

Induced pluripotent stem cells fascinate me :D

neurosciencestuff:

Human Induced Pluripotent Stem Cell-Derived Models to Investigate Human Cytomegalovirus Infection in Neural Cells

Human cytomegalovirus (HCMV) infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS) cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs), neural progenitor cells (NPCs) and neurons suggests that (i) iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii) Neural stem cells have impaired differentiation when infected by HCMV; (iii) NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv) most iPS-derived neurons are not permissive to HCMV infection; and (v) infected neurons have impaired calcium influx in response to glutamate.

Induced pluripotent stem cells fascinate me :D


‘Different kind of stem cell’ possesses attributes favoring regenerative medicine
A research team at Georgetown Lombardi Comprehensive Cancer Center say the new and powerful cells they first created in the laboratory a year ago constitute a new stem-like state of adult epithelial cells. They say these cells have attributes that may make regenerative medicine truly possible.
In the November 19 online early edition of the Proceedings of the National Academy of Sciences (PNAS), they report that these new stem-like cells do not express the same genes as embryonic stem cells and induced pluripotent stem cells (iPSCs) do. That explains why they don’t produce tumors when they grow in the laboratory, as the other stem cells do, and why they are stable, producing the kind of cells researchers want them to.
“These seem to be exactly the kind of cells that we need to make regenerative medicine a reality,” says the study’s senior investigator, chairman of the department of pathology at Georgetown Lombardi, a part of Georgetown University Medical Center.
This study is a continuation of work that led to a breakthrough in December 2011 when Schlegel and his colleagues demonstrated that he and his team had designed a laboratory technique that keep both normal as well as cancer cells alive indefinitely — which previously had not been possible.
They had discovered that adding two different substances to these cells (a Rho kinase inhibitor and fibroblast feeder cells) pushes them to morph into stem-like cells that stay alive indefinitely. When the two substances are withdrawn from the cells, they revert back to the type of cell that they once were. They dubbed these cells conditionally reprogrammed cells (CRCs).

‘Different kind of stem cell’ possesses attributes favoring regenerative medicine

A research team at Georgetown Lombardi Comprehensive Cancer Center say the new and powerful cells they first created in the laboratory a year ago constitute a new stem-like state of adult epithelial cells. They say these cells have attributes that may make regenerative medicine truly possible.

In the November 19 online early edition of the Proceedings of the National Academy of Sciences (PNAS), they report that these new stem-like cells do not express the same genes as embryonic stem cells and induced pluripotent stem cells (iPSCs) do. That explains why they don’t produce tumors when they grow in the laboratory, as the other stem cells do, and why they are stable, producing the kind of cells researchers want them to.

“These seem to be exactly the kind of cells that we need to make regenerative medicine a reality,” says the study’s senior investigator, chairman of the department of pathology at Georgetown Lombardi, a part of Georgetown University Medical Center.

This study is a continuation of work that led to a breakthrough in December 2011 when Schlegel and his colleagues demonstrated that he and his team had designed a laboratory technique that keep both normal as well as cancer cells alive indefinitely — which previously had not been possible.

They had discovered that adding two different substances to these cells (a Rho kinase inhibitor and fibroblast feeder cells) pushes them to morph into stem-like cells that stay alive indefinitely. When the two substances are withdrawn from the cells, they revert back to the type of cell that they once were. They dubbed these cells conditionally reprogrammed cells (CRCs).

bpod-mrc:

Picture of Health
Stem cells are seen here changing into star-shaped brain cells – in an experiment that also transformed science into art. The beauty of scientific images from this and other research projects involving stem cells inspired molecular biologist Mina Gouti to print a selection onto canvas for public viewing. As part of her exhibition, groups of children and writers were invited to describe what they saw, using their imagination. One seven-year-old boy likened the image here to moonlit raindrops falling onto a window, while a writer saw the pattern on an aunt’s favourite summer dress. Twenty images, some of them digitally enhanced for artistic purposes, were shown in the Athens exhibition, followed by a second exhibition with twice as many. Now, Mina is hoping to organise a future exhibition in London.
Written by Mick Warwicker
—

Mina Gouti, MRC NIMR
Biomedical Research Foundation of the Academy of Athens, Greece
Image exhibited in Stem Cell Metamorphoses: “Three glances into the original cell of our existence”

bpod-mrc:

Picture of Health

Stem cells are seen here changing into star-shaped brain cells – in an experiment that also transformed science into art. The beauty of scientific images from this and other research projects involving stem cells inspired molecular biologist Mina Gouti to print a selection onto canvas for public viewing. As part of her exhibition, groups of children and writers were invited to describe what they saw, using their imagination. One seven-year-old boy likened the image here to moonlit raindrops falling onto a window, while a writer saw the pattern on an aunt’s favourite summer dress. Twenty images, some of them digitally enhanced for artistic purposes, were shown in the Athens exhibition, followed by a second exhibition with twice as many. Now, Mina is hoping to organise a future exhibition in London.

Written by Mick Warwicker

afracturedreality:

Individual murine tail hair follicles are imaged with a Zeiss LSM510 confocal microscope. Stem cells are labeled green by the retention of H2BGFP, and all cells are stained red with the membrane dye FM464. This frame comes from a 3D reconstruction of a ~120 micron z stack obtained with a 20x objective (Zeiss Software).

The human scalp sheds ~50–100 hairs each day. So what keeps you from balding? Stem cells, of course. At the base of a hair follicle, a population of stem cells wraps around the follicle, creating a compartment, called the “bulge.” These bulge stem cells have high proliferative capacity and are multipotent. In transplants, these cells can regenerate not only lost hair but also sebaceous glands and epidermis, too.

By the Valentina Greco Laboratory, Yale School of Medicine

afracturedreality:

Individual murine tail hair follicles are imaged with a Zeiss LSM510 confocal microscope. Stem cells are labeled green by the retention of H2BGFP, and all cells are stained red with the membrane dye FM464. This frame comes from a 3D reconstruction of a ~120 micron z stack obtained with a 20x objective (Zeiss Software).

The human scalp sheds ~50–100 hairs each day. So what keeps you from balding? Stem cells, of course. At the base of a hair follicle, a population of stem cells wraps around the follicle, creating a compartment, called the “bulge.” These bulge stem cells have high proliferative capacity and are multipotent. In transplants, these cells can regenerate not only lost hair but also sebaceous glands and epidermis, too.

By the Valentina Greco Laboratory, Yale School of Medicine