Oh Yeah, Developmental Biology!
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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.…
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
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.
A magnified view of human embryonic stem cells.
Image by Melanie Ivancic, Joseph Klim, and Laura Kiessling, University of Wisconsin-Madison.
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).
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
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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
Sperm stem cells restore male fertility
Men who lose the ability to produce sperm after chemotherapy might one day be able to regain their fertility. That’s because, for the first time, infertility has been reversed in a male primate using an injection of stem cells.
Cancer drugs often work by destroying rapidly dividing cells, as these are a typical feature of cancer. Unfortunately, the drugs can also kill other rapidly dividing cells, including those that produce sperm. Some men choose to freeze sperm samples before therapy so they can use them for artificial insemination at a later date, but this is not an option for boys who have not yet reached puberty.
Kyle Orwig at the University of Pittsburgh School of Medicine in Pennsylvania may have a solution. He says that while boys don’t make sperm cells, they do possess “spermatogonial” stem cells that will eventually produce them.
To see if these stem cells could be used to restore fertility, Orwig and his team took samples of the cells from the testes of prepubescent and adult male rhesus macaques, and froze them. The monkeys were then given chemotherapy agents known to shut down sperm production. A few months later, the researchers injected each monkey’s own spermatogonial stem cells back into its testes.
Sperm production was re-established in nine of the 12 adult animals and started normally in three out of five prepubescent animals once they reached maturity. The resulting sperm were used to fertilise eggs and produce healthy embryos.
“I think this is the best option we have ever had,” says Renee Reijo Pera, director of Stanford University’s Center for Human Embryonic Stem Cell Research and Education, who wasn’t involved in the study. “I know a lot of people have thought about doing this before but no has ever been able to successfully demonstrate this in a clinical setting with a species genetically very similar to us.”
Orwig says there are some concerns that implanting stem cells could reintroduce cancer cells that may have been present in the original tissue. However, centres in the US and Europe are already banking testicular tissue for boys in the hope that new stem cell-based therapies will become available.
“In the most optimistic scenario our research suggests a man could have his own stem cells transplanted, giving him the opportunity to have children via natural intercourse,” Orwig says. It’s not yet ready for clinical translation, he says, “but it’s an important step forward”.
Journal reference: Cell Stem Cell, DOI: 10.1016/j.stem.2012.07.017
Human embryonic stem cell
A colony of human embryonic stem cells (light blue) growing on fibroblasts (dark blue). (Flickr : CIRM)
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