Gremlins Sabotage the Mechanisms of Cancer Stem Cell Differentiation

Gremlins Sabotage the Mechanisms of Cancer Stem Cell Differentiation - that's not a joke. It's a title of the new paper at Cancer Cell Volume 25, Issue 6, 16 June 2014, Pages 716–717. Joan Seoane made an interesting research on cancer stem cells. 

Here is the abstract: BMP is highly expressed in glioblastoma and promotes differentiation of cancer stem cells (CSCs). Recently, Yan and colleagues found the explanation to this apparent paradox by showing that the antagonist of BMP, Gremlin1, is secreted by CSCs to protect them against the BMP-induced differentiation.

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My cartoon about MSC and HSC from Umbilical Cord

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Biomaterials for Stem Cell Therapy - CRC Press Book

Biomaterials for Stem Cell Therapy - CRC Press Book

Focused on stem cell applications, this book bridges the fields of biomaterials, offering new insights into constructing and regenerating tissues and organs. Its unique feature is linking diseases of the human body to current thinking on how to deal with them in the context of current concepts and technologies by means of an in-depth focus on biomaterials. The book assembles recent advances and covers a range of topics related to stem cell biology, biomaterials and technological approaches such as bioreactors written by top researchers in the field. Stem cells of both embryonic and adult origin are discussed with applications ranging, but not limited to, nerve regeneration, liver, pancreas, skin, trachea, cartilage and bone repair and cardiovascular therapy. Developments in the field reflecting the design and construction of the human body and its principal anatomy are discussed from a materials point of view.

The book will be a valuable tool for biomaterial scientists, tissue engineers, clinicians as well as stem cell biologists involved in basic research and applications of adult and embryonic stem cells. It will also be a source of reference for students in biotechnology, biomedical engineering, biology, biochemistry, materials sciences, pharmaceuticals, and veterinary and human medicine.

STEM CELLS & FUN

3-D printers can produce gun parts, aircraft wings, food and a lot more, but this new 3-D printed product may be the craziest thing yet: human embryonic stem cells.

Rebecca Boyle - Popular Science

3-D printers can produce gun parts, aircraft wings, food and a lot more, but this new 3-D printed product may be the craziest thing yet: human embryonic stem cells. Using stem cells as the "ink" in a 3-D printer, researchers in Scotland hope to eventually build 3-D printed organs and tissues. A team at Heriot-Watt University used a specially designed valve-based technique to deposit whole, live cells onto a surface in a specific pattern.

This article originally appeared at Popular Science.

The cells were floating in a "bio-ink," to use the terminology of the researchers who developed this technique. They were able to squeeze out tiny droplets, containing five cells or fewer per droplet, in a variety of shapes and sizes. To produce clumps of cells, the team printed out cells first and then overlaid those with cell-free bio-ink, resulting in larger droplets or spheroids of cells. The cells would group together inside these spheroids. Spheroid size is key, because stem cells need certain conditions to work properly. This is why very precisely controlled 3-D printing could be so valuable for stem cell research.

After being squeezed out of a thin valve, the cells were still alive and viable, and able to transform into any other cell in the body, the researchers say. It's the first time anyone has printed human embyronic stem cells, said lead researcher Will Wenmiao Shu, a professor at Heriot-Watt. But ... why?

Eventually, they could be used to print out new tissues, or as filler inside existing organs, which would be regenerated. It could even serve to limit animal testing for new drug compounds, allowing them to be tested on actual human tissue, said Jason King, business development manager at Roslin Cellab, one of the research partners. "In the longer term, [it could] provide organs for transplant on demand, without the need for donation and without the problems of immune suppression and potential organ rejection," he said in a statement.

The team took stem cells from an embryonic kidney and from a well-studied embryonic cell line, and grew them in culture. They had to build a custom reservoir — let's call it an inkwell — to safely house the delicate cells, and then they added some large-diameter nozzles. A pressurized air supply pumps the cells from the inkwell into the valves, which contain pressurized nozzles on the end. The team could control the amount of cells dispensed by changing any of the factors, including the pneumatic pressure, nozzle diameter or length of time the nozzle stayed open.

At first the researchers printed droplets, but ultimately, they were so precise that they made cell spheroids in a variety of shapes and sizes, like the university logo above. One interesting wrinkle: The cells also formed spheroids in the inkwells. More work needs to be done to explain that.

The researchers also took several steps to make sure the cells survived the printing process. Examining the results of several experiments, they found 99 percent of the cells were still viable after running through the valve-based printer. "This confirms that this printing process did not appear to damage the cells or affect the viability of the vast majority of dispensed cells," they write in their paper, which is being published in the IOP regenerative medicine journal Biofabrication.

Stem cells are powerful because they can develop into any cell in the body. Embryonic stem cells, which are taken from human embryos in the earliest stages of development, can be developed into stem cell lines that can be grown indefinitely. This is kind of controversial, especially in the US. But medical researchers think they could be hugely promising for a whole host of human ailments — stem cells could differentiate into neurons, potentially replacing the ones lost in degenerative diseases like Alzheimer's; or they could differentiate into pancreatic cells, curing diabetes; and so on.

Using a 3-D printer to produce gun parts has been pretty controversial, especially during the ongoing post-Connecticut-shooting gun debate. But that may be nothing compared to this.

http://io9.com/5981832/a-3d-printer-that-generates-human-embryonic-stem-cells

Leprosy & stem cells

Leprosy is a bacterial disease that spreads to muscles and other tissues in the body, causing neurodegeneration and muscle weakness. A new study, published by Cell Press January 17th in the journal Cell, reveals that the bacteria responsible for leprosy spread infection by hijacking specialized cells in the adult nervous system, reprogramming them into a stem cell-like state, and converting them to muscle-like cells. These findings could lead to the development of new therapeutic strategies for combating bacterial infections and degenerative diseases as well as new tools for regenerative medicine.
"This is the first demonstration of how a bacterial pathogen could use the genomic plasticity of our adult body tissue cells for generating stem cells naturally during infection," says senior study author Anura Rambukkana of the University of Edinburgh. "Our findings provide new directions for preventing the progression of infection at an early stage and for reprogramming adult tissue cells to stem cells for regenerating damaged tissues in the body."
Leprosy is caused by Mycobacterium leprae (M. leprae), which initially infects adult Schwann cells, cells which usually wrap around nerves to insulate electrical signals passing through, in the peripheral nervous system. The leprosy bacteria must then spread to other tissues to transmit infection, but how they do so has been a long-standing mystery. Because Schwann cells can convert into dedicated repair cells to help adult nerves recover after injury, Rambukkana and his team suspected that M. leprae takes advantage of this remarkable plasticity to spread infection.
To test this idea, the researchers infected adult Schwann cells from mice with M. leprae. The bacteria reprogrammed these cells into a stem cell-like state—in which they're capable of converting into diverse cell types—by turning off genes that are active in the mature form of these cells and turning on genes that are expressed during embryonic development. M. leprae then converted these immature cells into muscle-like cells and spread infection to muscles through this process. When the researchers injected bacteria-laden immature cells into the muscles of adult mice, the bacteria spread to different types of muscle cells.
"Our study shows that host cell reprogramming is perhaps a necessary event in early bacterial infection that promotes the spread of infection," Rambukkana says. "By identifying early molecular targets or diagnostic biomarkers related to the reprogramming process, it will be possible to prevent the progression of infection and thus nerve damage and subsequent disability in patients."

Cell, Masaki et al.: "Reprogramming Adult Schwann Cells to Stem Cell-Like Cells by Leprosy Bacilli Promotes Dissemination of Infection."

Interesting news! Thanks to  http://www.eurekalert.org/pub_releases/2013-01/cp-nii011013.php 

positive interim safety results of its Phase IIa study of its allogeneic stem cell therapy

Cell Therapy pioneer TiGenix has announced positive interim safety results of its Phase IIa study of its allogeneic stem cell therapy Cx611 in rheumatoid arthritis (RA), showing a good safety profile at all three doses of the product that were administered in the trial.
This is a significant development in the field of stem cell therapy because Cx611 is an allogeneic product that potentially could be made available off-the-shelf and used to treat any patient, without concerns that the foreign cells will cause an immune reaction. In addition, TiGenix says the product, which is made from adult stem cells derived from human adipose (fat) tissue, has a broad anti-inflammatory effect and could also be used to treat other autoimmune disorders.
If positive, the final results of the trial, due in April 2013, will set the scene for the further development of Cx611. The TiGenix trial is the most advanced in the world using stem cells to treat rheumatoid arthritis. Along with other cell therapies that are advancing in development such as ReNeuron plc’s neuronal cell therapy for treating the after-effects of stroke, and the human embryonic stem cell-based treatment for macular degeneration (a major cause of blindness) which Pfizer is developing in collaboration with scientists at University College London, the TiGenix news on Cx611 underlines Europe’s leading position in cell therapy and regenerative medicine.
These three products can all trace their origins back to publicly-funded basic research, providing a potent demonstration of the importance of continuing to support academic research in the field, and of building and reinforcing the clinical and regulatory framework for translating this research into commercial products.
Moves by some MEPs to end European Union funding for embryonic stem cell research in the proposed €80 billion Horizon 2020 R&D programme are widely seen as a threat to Europe’s standing in cell therapy and regenerative medicine. Science|Business brought together experts from patients’ groups, research charities, academe, industry, science and economic policy, and regulators, to discuss the implications of an end to EU support for embryonic stem cell research, and scope what needs to be done to build the regenerative medicines market in Europe, to the benefit of patients and the economy. The full report is now available here.

http://www.sciencebusiness.net/news/75982/European-cell-therapy-pioneer-makes-further-advance?utm_source 

Another one stem cell fraud

Wired news... Stem cell research becomes a strange place... Here's some recent events:

Shane Mayack, a former post-doc in Harvard lab of Amy Wagers, a rising star in the stem cell field, has been sanctioned by the Office of Research Integrity for misconduct.
Mayack, who has defended her actions on this blog as honest error — albeit sloppiness — and has not admitted to wrongdoing, must undergo supervision if she receives any federal grant funding over the next three years, under the voluntary agreement.
Here’s the notice, which appeared in the Federal Register this week (and which theBoston Globe was first to report):

Based on the report of an investigation conducted by the Joslin Diabetes Center (Joslin) and additional analysis conducted by ORI in its oversight review, ORI found that Dr. Shane Mayack, former postdoctoral fellow, Department of Developmental and Stem Cell Biology, Joslin, engaged in research misconduct in research supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), grants T32 DK07260–29 and P30 DK036836 and the 2008 NIH Director’s New Innovator Award Program grant DP2 OD004345–01.
ORI found that Respondent engaged in research misconduct involving two (2) published papers:
• Mayack, S.R., Shadrach, J.L., Kim, F.S., & Wagers, A.J. ‘‘Systemic signals regulate ageing and rejuventation of blood stem cell niches.’’ Nature 463:495–500, 2010.
• Mayack, S.R., & Wagers, A.J. ‘‘Osteolineage niche cells initiate hemotopoietic stem cell mobilization.’’ Blood 112:519–531, 2008.
As a result of Joslin’s investigation, both Nature 463:495–500, 2010 (hereafter referred to as the ‘‘Nature paper’’) and Blood 112:519–531, 2008 (hereafter referred to as the ‘‘Blood paper’’) have been retracted by the corresponding author.
Specifically, ORI found that:
• Respondent falsely represented von Kossa-stained bone nodule images in two (2) published papers:
Figure 2B in the Blood paper was copied from an unrelated published experiment in Figure 3, J Orth Surg Res 1:7, 2006, and was used to falsely represent Respondent’s own experiment for bone nodules formed in cultured osteoblastic niche cells.
b. Figure S2c in the Nature paper was copied from an online image for an unrelated experiment (at http://skeletalbiology.uchc.edu/30_ResearchProgram/304_gap/3042_Lineage%20in%20Vitro/3042_01_aCellCult.htm#mCOB) and was used to falsely represent Respondent’s own experiment for bone nodules formed in osteoblastic niche cells from young and aged mice.
• Respondent falsely represented eight (8) flow cytometry contour plots as different experimental results by using identical plots but with different labels and different numerical percentages.
Specifically, the following contour plots in the Blood paper, the Nature paper, an earlier version of the Nature paper submitted to Science (hereafter referred to as the ‘‘Science manuscript’’), and a July 2008 PowerPoint presentation were identical but were labeled differently:
a. Panels 4 and 2 in Figure 6C, Blood paper, and panels 1 and 2, respectively, in supplementary Figure 3b, Nature paper
b. Panel 3 in Figure 6C, Blood paper, and panel 1 in Figure 2, July 2008 PowerPoint presentation
Panels 1 and 2, Figure 2b, Science manuscript, and panels 2 and 3, respectively, in Figure 2, July 2008 PowerPoint presentation
Panels 2, 3, and 4, supplemental Figure 4A, Blood paper, and panels 3, 1, and 2, respectively, in Figure 4B, Science manuscript
Both the Respondent and HHS want to conclude this matter without further expenditure of time or other resources and have entered into a Voluntary Settlement Agreement to resolve this matter. Respondent neither admits nor denies ORI’s finding of research misconduct. This settlement does not constitute an admission of liability on the part of the Respondent.
Nearly two years have passed since we first wrote about Mayack. At the time, Wagers’ group had just retracted a 2010 Nature paper — with a notable exception: Mayack refused to sign the notice, nor did she sign the notice for the retraction of the Blood paper, which appeared in late 2011.
As she wrote on this blog:

… the readers of Retraction Watch are no doubt aware that in October 2010, a paper that I co-authored was retracted fromNature and a notice of concern was posted regarding a second paper published in Blood.
So, what went wrong?
The answer to that question begins with the fact that errors, not fabrications, were made in assembling figures for these manuscripts. I am likely the one who made these errors.
Mayack reiterated that position in a comment, through her attorney, to us today:

I remain deeply sorry to the scientific community for mistakes made during the preparation of figures corresponding to some of the work I performed as a postdoc at Harvard Medical School. These were mistakes in representation and presentation of the data, as corroborated by ORI’s findings of ‘falsely presented’, and were not due to fabrication, falsification, or plagiarism of scientific results. I am deeply committed to moving forward and strive to contribute positively to the advancement of science, which has always been my utmost interest.
Wagers recently received tenure.

http://retractionwatch.wordpress.com/2012/08/29/ori-finds-harvard-stem-cell-lab-post-doc-mayack-manipulated-images/