Page 22«..10..21222324

A new approach to treating type I diabetes? Gut cells transformed into insulin factories

By raymumme

Public release date: 11-Mar-2012 [ | E-mail | Share ]

Contact: Karin Eskenazi ket2116@columbia.edu 212-342-0508 Columbia University Medical Center

NEW YORK, NY -- A study by Columbia researchers suggests that cells in the patient's intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

The researchconducted in micewas published 11 March 2012 in the journal Nature Genetics.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai is a postdoctoral fellow in Dr. Accili's lab.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisionsFoxo1the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood.

"Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients," Dr. Accili says.

See more here:
A new approach to treating type I diabetes? Gut cells transformed into insulin factories

To Read More: A new approach to treating type I diabetes? Gut cells transformed into insulin factories
categoriaIPS Cell Therapy commentoComments Off on A new approach to treating type I diabetes? Gut cells transformed into insulin factories | dataMarch 12th, 2012
Read All

Gut cells transformed into insulin factories 'could help to treat type I diabetes'

By LizaAVILA

London, Mar 12 (ANI): A new study conducted by scientists suggests a new approach that could give patients the ability to make their own insulin-producing cells without a stem cell transplant.

Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose.

Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed.

Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels.

If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai and Domenico Accili from Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

They found that when they turned off a gene known to play a role in cell fate decisions-Foxo1-the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood.

Excerpt from:
Gut cells transformed into insulin factories 'could help to treat type I diabetes'

To Read More: Gut cells transformed into insulin factories 'could help to treat type I diabetes'
categoriaIPS Cell Therapy commentoComments Off on Gut cells transformed into insulin factories 'could help to treat type I diabetes' | dataMarch 12th, 2012
Read All

New approach to treating type 1 diabetes? Transforming gut cells into insulin factories

By raymumme

ScienceDaily (Mar. 11, 2012) A study by Columbia researchers suggests that cells in the patient's intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

The research -- conducted in mice -- was published 11 March 2012 in the journal Nature Genetics.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai is a postdoctoral fellow in Dr. Accili's lab.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisions -- Foxo1 -- the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood. "Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients," Dr. Accili says.

"Nobody would have predicted this result," Dr. Accili adds. "Many things could have happened after we knocked out Foxo1. In the pancreas, when we knock out Foxo1, nothing happens. So why does something happen in the gut? Why don't we get a cell that produces some other hormone? We don't yet know."

Insulin-producing cells in the gut would be hazardous if they did not release insulin in response to blood glucose levels. But the researchers say that the new intestinal cells have glucose-sensing receptors and do exactly that.

The insulin made by the gut cells also was released into the bloodstream, worked as well as normal insulin, and was made in sufficient quantity to nearly normalize blood glucose levels in otherwise diabetic mice.

Read the rest here:
New approach to treating type 1 diabetes? Transforming gut cells into insulin factories

To Read More: New approach to treating type 1 diabetes? Transforming gut cells into insulin factories
categoriaIPS Cell Therapy commentoComments Off on New approach to treating type 1 diabetes? Transforming gut cells into insulin factories | dataMarch 12th, 2012
Read All

Presentations at the Society of Toxicology Annual Meeting Demonstrate Superior Predictivity of Cellular Dynamics …

By NEVAGiles23

MADISON, Wis., March 8, 2012 /PRNewswire/ --Cellular Dynamics International, Inc. (CDI), the world's largest commercial producer of human induced pluripotent stem (iPS) cell lines and tissue cells for drug discovery and safety, today announced several customer presentations of studies employing the company's iCell products at the Society of Toxicology (SOT) Annual Meeting on March 11 to 15 in San Francisco. A number of these studies demonstrate the superior predictivity of CDI's human iPS cell-derived products compared to other cell models, such as animal models and immortalized cell lines, which are historically used in pharmaceutical drug discovery and toxicity testing.

Customers will present 11 abstracts employing CDI's human cells in their research during the SOT meeting. Several of these compare the superior ability of CDI's iCell Cardiomyocytes and iCell Hepatocytes to predict toxic responses to currently available cell models. Among them:

Puppala, D et al. (Abstract 420 Poster Board -642; Pfizer, Inc.) compared the ability of iCell Cardiomyocytes to a rat cardiac-derived cell line (H9C2) to predict the toxicity of 10 known in vivo cardiac toxins that were not flagged by the company's current in vitro assay systems. They found that iCell Cardiomyocytes showed increases in several toxicity signals and were more accurate in detecting cardiotoxicity than the rat cell line.

Guo, L et al. (Abstract 1168 Poster Board -433; Hoffman-La Roche) utilized sets of reference and internal compounds to determine the accuracy with which iCell Cardiomyocytes can predict arrhythmic effects. Based on drug-induced changes in beating pattern, iCell Cardiomyocytes correctly identified 17 of 19 reference compounds known to cause abnormal ECG patterns in humans and 17 of 17 internal compounds known to cause arrhythmia in non-rodent animals. These results demonstrate the predictive value of utilizing iCell Cardiomyocytes to identify proarrhythmic compounds.

Hong, S et al. (Abstract 1149 Poster Board -414; Bristol-Myers Squibb) evaluated the effects of three drug compounds using both iCell Cardiomyocytes and fetal rat cardiomyocytes utilizing multi-electrode array (MEA) assays. For all three compounds, iCell Cardiomyocytes were better suited than the fetal rat cardiomyocytes at predicting adverse in vivo effects, including those effects that were not discovered until small-scale clinical trials.

Kameoka, S et al. (Abstract 519 Poster Board -237; Hoffman-La Roche) compared the toxicity of three drug candidates previously tested on dog hepatocytes to iCell Hepatocytes and primary human hepatocytes. In dogs, two of the three compounds caused liver toxicity. The profiles of the two toxic compounds were almost identically recapitulated in vitro for both the primary human hepatocytes and iCell Hepatocytes. This study demonstrated that iCell Hepatocytes may be a valuable human model to predict hepatic toxicity in vitro.

Additional SOT presentations employing CDI's iCell products can be found on the SOT Annual Meeting website or at http://www.cellulardynamics.com/sot2012/posters.html.

"These studies are important contributors to the collective understanding that human in vitro cellular model systems are superior to animal models and immortalized cell lines when studying questions of human biology," said Chris Parker, chief commercial officer of CDI. "We recognize that iPS cell-derived tissues are a relatively new model for drug discovery and toxicity testing and must be validated and shown to be superior. It is gratifying that our pharmaceutical customers are presenting data validating the performance characteristics of our heart and liver cells in such an open scientific forum as the Society of Toxicology Annual Meeting. Third-party validation of iCell product performance coupled with CDI's proven ability to deliver human cells in the quantity, quality and purity required for pharmaceutical, biomedical and basic research positions us well for supplying customers with the human cells they need to improve healthcare."

About Cellular Dynamics International, Inc.Cellular Dynamics International, Inc. (CDI) is a leading developer of next-generation stem cell technologies for drug development, cell therapy, tissue engineering and organ regeneration. CDI harnesses its unique manufacturing technology to produce differentiated tissue cells from any individual's stem cell line in industrial quality, quantity and purity. CDI is accelerating the adoption of pluripotent stem cell technology, adapting its methods to fit into standard clinical practice by the creation of individual stem cell lines from a standard blood draw. CDI was founded in 2004 by Dr. James Thomson, a pioneer in human pluripotent stem cell research at the University of Wisconsin-Madison. CDI's facilities are located in Madison, Wisconsin. See http://www.cellulardynamics.com.

MEDIA CONTACTS:Joleen Rau Senior Director, Marketing & Communications Cellular Dynamics International, Inc. 608 310-5142 jrau@cellulardynamics.com

Read the original:
Presentations at the Society of Toxicology Annual Meeting Demonstrate Superior Predictivity of Cellular Dynamics ...

To Read More: Presentations at the Society of Toxicology Annual Meeting Demonstrate Superior Predictivity of Cellular Dynamics …
categoriaIPS Cell Therapy commentoComments Off on Presentations at the Society of Toxicology Annual Meeting Demonstrate Superior Predictivity of Cellular Dynamics … | dataMarch 8th, 2012
Read All

Horizon in new super-cell elite

By daniellenierenberg

Cambridge personalised medicines pioneer Horizon Discovery Ltd has landed another showpiece deal as part of a new super-cell consortium.

Business Weekly understands that the UK company stands to make a seven-figure haul over the lifetime of an EU-funded project aimed at understanding hES cell differentiation control.

Horizon provides research tools to support the development of personalised medicines. It has joined the EU-FP7 funded ‘4D-Cell-Fate’ consortium  whose aim is to shed light on how stem cell re-programming and differentiation is regulated at the epigenetic level.

As a member of the consortium, Horizon will generate cell-lines harbouring endogenous pathway reporter genes and labelled versions of specific epigenetic target proteins to study their function.

Commercialisation of the output of the programme will be governed by a consortium agreement defined by EU regulation.

4DCellFate brings together 12 groups from nine countries, including academics, research-intensive SMEs, and Pharma, each an international leader in its field, combining expertise in a wide range of cutting-edge technologies and scientific approaches.

The aim of the 4D CellFate project, which is currently funded for five years, is to establish an integrated approach to explore the structure and function of the large multi-protein epigenetic complexes that are involved in control of stem cell self-renewal, lineage commitment, and differentiation.

Horizon will use its proprietary virally-mediated gene-engineering technology, GENESIS™, to alter endogenous genes in hES cells (e.g. via tagging with GFP and HaloTag® technologies) with unprecedented accuracy and precision.

By gaining a greater insight into how Polycomb Repressive Complexes (PRCs), and Nucleosome Remodelling and Deacetylation complexes (NuRD) control stem cell differentiation, it is hoped that better methods will be identified to generate ethical sources of ‘iPS’ stem cells and direct the fate of stem cells into the many forms of specific tissue types that are needed for disease therapy.

Dr Chris Torrance, CSO of Horizon, said: “Generating stem cells and differentiated cell types with greater precision, definition and safety are key areas for delivering on the great promise that stem cell-based therapies could bring to many disease areas.

“Horizon’s gene targeting technology will play a key role in helping to dissect key biological pathways in the fate of stem cells as part of the 4D Cell Fate project. Through this process, new and important approaches to disease therapy will be determined.”

CEO Dr Darrin Disley added: “Our company has a commitment to active involvement in cutting-edge research with leading experts in translational fields, including bringing the power of rAAV-mediated gene targeting technology to the 4D Cell Fate project.”

Read the original:
Horizon in new super-cell elite

To Read More: Horizon in new super-cell elite
categoriaIPS Cell Therapy commentoComments Off on Horizon in new super-cell elite | dataFebruary 16th, 2012
Read All

Research and Markets: Primary and Stem Cells: Gene Transfer Technologies and Applications

By daniellenierenberg

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/fc9dd6/primary_and_stem_c) has announced the addition of John Wiley and Sons Ltd's new book "Primary and Stem Cells: Gene Transfer Technologies and Applications" to their offering.

This book describes basic cell engineering methods, emphasizing stem cell applications, and use of the genetically modified stem cells in cell therapy and drug discovery. Together, the chapters introduce and offer insights on new techniques for engineering of stem cells and the delivery of transgenes into stem cells via various viral and non-viral systems. The book offers a guide to the types of manipulations currently available to create genetically engineered stem cells that suit any investigator's purpose, whether it's basic science investigation, creation of disease models and screens, or cells for therapeutic applications.

Key Topics Covered:

PART I: CLONING AND GENE DELIVERY

1. DNA Assembly Technologies Based on Homologous Recombination

2. Multigene Assembly for Construction of Synthetic Operons: Creation and Delivery of an Optimized All-IN-One Expression Construct for Generating Mouse iPS Cells

3. Strategies for the Delivery of Naked DNA

PART II: NONINTEGRATING TECHNOLOGIES

4. Episomal Vectors

5. Nonintegrating DNA Virus

6. Nonintegrating RNA Viruses

7. Protein Delivery

PART III: INTEGRATING TECHNOLOGIES

8. Sleeping Beauty Transposon-Mediated Stable Gene Delivery

9. Integrating Viral Vectors for Gene Modifications

10. Bacteriophage Integrases for Site-Specific Integration

11. Improving Gene Targeting Efficiency in Human Pluripotent Stem Cells

PART IV: APPLICATIONS

12. Modified Stem Cells as Disease Models and in Toxicology Screening

13. Screening and Drug Discovery

INDEX

Author:

UMA LAKSHMIPATHY is a principal investigator at Life Technologies. She has a PhD in life sciences, with academic and industry experience in molecular biology and stem cells. Dr. Lakshmipathy holds four patents and has authored more than forty publications.

BHASKAR THYAGARAJAN is a program manager at Life Technologies. He has a PhD in pharmacology, with expertise in the areas of molecular biology, DNA recombination, gene and cell therapy, and protein purification. He holds one patent and has authored more than twenty publications.

For more information visit http://www.researchandmarkets.com/research/fc9dd6/primary_and_stem_c

Read the rest here:
Research and Markets: Primary and Stem Cells: Gene Transfer Technologies and Applications

To Read More: Research and Markets: Primary and Stem Cells: Gene Transfer Technologies and Applications
categoriaIPS Cell Therapy commentoComments Off on Research and Markets: Primary and Stem Cells: Gene Transfer Technologies and Applications | dataFebruary 15th, 2012
Read All

Radiation therapy transforms breast cancer cells into cancer stem cells

By daniellenierenberg

Washington, Feb 14 (ANI): Researchers have shown for the first time that radiation treatment -despite killing half of all tumour cells during every cycle - transforms other cancer cells into treatment-resistant breast cancer stem cells.

According to researchers with the UCLA Department of Radiation Oncology at UCLA's Jonsson Comprehensive Cancer Center, the generation of these breast cancer stem cells counteracts the otherwise highly efficient radiation treatment.

If scientists can uncover the mechanisms and prevent this transformation from occurring, radiation treatment for breast cancer could become even more effective, said study senior author Dr. Frank Pajonk, an associate professor of radiation oncology and Jonsson Cancer Center researcher.

"We found that these induced breast cancer stem cells (iBCSC) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells (iPS) in regenerative medicine," said Pajonk, who also is a scientist with the Eli and Edythe Broad Center of Regenerative Medicine at UCLA.

"It was remarkable that these breast cancers used the same reprogramming pathways to fight back against the radiation treatment."

"Controlling the radiation resistance of breast cancer stem cells and the generation of new iBCSC during radiation treatment may ultimately improve curability and may allow for de-escalation of the total radiation doses currently given to breast cancer patients, thereby reducing acute and long-term adverse effects," the study stated.

There are very few breast cancer stem cells in a larger pool of breast cancer cells. In this study, Pajonk and his team eliminated the smaller pool of breast cancer stem cells and then irradiated the remaining breast cancer cells and placed them into mice.

Using a unique imaging system Pajonk and his team developed to visualize cancer stem cells, the researchers were able to observe their initial generation into iBCSC in response to the radiation treatment.

The newly generated iBCSC were remarkably similar to breast cancer stem cells found in tumors that had not been irradiated, Pajonk said.

The team also found that the iBCSC had a more than 30-fold increased ability to form tumors compared to the non-irradiated breast cancer cells from which they originated.

Pajonk said that the study unites the competing models of clonal evolution and the hierarchical organization of breast cancers, as it suggests that undisturbed, growing tumors maintain a small number of cancer stem cells.

However, if challenged by various stressors that threaten their numbers, including ionizing radiation, the breast cancer cells generate iBCSC that may, together with the surviving cancer stem cells, repopulate the tumour.

"What is really exciting about this study is that it gives us a much more complex understanding of the interaction of radiation with cancer cells that goes far beyond DNA damage and cell killing," Pajonk said.

"The study may carry enormous potential to make radiation even better."

Pajonk stressed that breast cancer patients should not be alarmed by the study findings and should continue to undergo radiation if recommended by their oncologists.

"Radiation is an extremely powerful tool in the fight against breast cancer," he said.

"If we can uncover the mechanism driving this transformation, we may be able to stop it and make the therapy even more powerful," Pajonk added.

The study has been published in the online edition of peer-reviewed journal Stem Cells. (ANI)

Originally posted here:
Radiation therapy transforms breast cancer cells into cancer stem cells

To Read More: Radiation therapy transforms breast cancer cells into cancer stem cells
categoriaIPS Cell Therapy commentoComments Off on Radiation therapy transforms breast cancer cells into cancer stem cells | dataFebruary 14th, 2012
Read All

Life Technologies Scientist Uma Lakshmipathy presents, "Solving Challenges in the Generation of Induced Pluripotent …

By NEVAGiles23

Dr. Uma Lakshmipathy speaks at various conferences about work on the creation of integration-free induced pluripotent stem cells at high efficiency with Sendai Virus using the CytoTune™ -iPS Reprogramming Kit. Uma Lakshmipathy's next speaking engagement will be in Mid February at the Stem Cell Banking Conference in London.

Carlsbad, California (PRWEB) February 14, 2012

Uma's last presentation about the Generation of Induced Pluripotent Stem Cells summarized here was also recorded for viewing and placed on the Life Technologies website. (http://find.lifetechnologies.com/stemcells/umavideo/article)

The CytoTune™ - iPS Reprogramming Kit is a high efficiency, integration- free, easy-to-use somatic cell reprogramming kit used in the generation of induced pluripotent stem cells. This kit utilizes Sendai Virus particles of the four Yamanaka factors, which have been shown to be critical in the successful generation of induced pluripotent stem cells.

In her presentations, Uma Lakshmipathy discusses two current challenges faced when generating iPSC including low efficiency and expertise of users.

Low Efficiency

The most common method for generation of induced pluripotent stem cells is the transfection of the four Yamanaka factors using lentivirus or retrovirus. One of the biggest challenges for scientists right now is the low efficiency of iPSC generation. With difficult to transfect cell types or cells from older patients, efficiencies can be 0.001% or lower when using lentiviral or retroviral methods.

Expertise of Users

The second challenge is for users with little expertise that have a difficult time detecting these emerging iPSC colonies. When looking for pluripotent stem cells, people can either pick them up really easily or have trouble deciding what clones to place their bet on.

Efficiency & Safety of IPSC Generation

There are several methods which improve reprogramming efficiency including viral non-integrating and small molecule methods such as mRNA, microRNA and small molecules. The developers of the CytoTune™ -iPS Reprogramming Kit concentrated on a non-integrating viral method utilizing Sendai Virus, a negative sense RNA virus. Sendai Virus is able to infect a wide variety of cell types and generates induced pluripotent stem cells at efficiencies 100-fold higher than lentiviral or retroviral methods.

When comparing efficiency vs. safety of reprogramming methods, small molecules like microRNA, RNA and protein which don’t leave a footprint are safer for cell therapy research; however, the efficiency of generating induced pluripotent stem cells with these methods is pretty low at this point in time.

The highest efficiency so far has been achieved with viral methods such as Retrovirus and Lentivirus. More recently the CytoTune™ -iPS Reprogramming Kit actually exceeds the efficiency that can be obtained with these traditional viral systems and at the same time it is much safer because it is a non-integrating RNA virus. Therefore it will not leave a footprint in the iPSCs that are created.

The CytoTune™ -iPS Reprogramming Kit will:

    Reduce hands on time - enables successful iPS reprogramming in one simple transduction     Generate more cells - high efficiency reprogramming offers more iPS cells from a single experiment     Use in a broad range of experiments - lack of genomic integration and viral remnants allows use from basic to clinical research

Ease of Use

The CytoTune™ -iPS Reprogramming Kit provides a simple system for somatic cell reprogramming. For most cell types, the CytoTune™ -iPS Reprogramming Kit requires only one application of the virus for successful cell reprogramming, unlike other methods such as Lentivirus and mRNA which can require multiple rounds of transduction to produce iPS cells. Selection of colonies is also easier with the CytoTune™ –iPS Reprogramming Kit due to the lower number of non-induced pluripotent stem cells that are generated.

To view this presentation visit http://find.lifetechnologies.com/stemcells/umavideo/article

Uma Lakshmipathy's protocol, "Transfection of Human Embryonic Stem Cells" can be seen here http://bit.ly/y91Gpd

###

Jennifer Hornstein
Life Technologies
(760) 602-4577
Email Information

Go here to read the rest:
Life Technologies Scientist Uma Lakshmipathy presents, "Solving Challenges in the Generation of Induced Pluripotent ...

To Read More: Life Technologies Scientist Uma Lakshmipathy presents, "Solving Challenges in the Generation of Induced Pluripotent …
categoriaIPS Cell Therapy commentoComments Off on Life Technologies Scientist Uma Lakshmipathy presents, "Solving Challenges in the Generation of Induced Pluripotent … | dataFebruary 14th, 2012
Read All

Radiation treatment generates cancer stem cells from less aggressive breast cancer cells, study suggests

By daniellenierenberg

ScienceDaily (Feb. 13, 2012) — Breast cancer stem cells are thought to be the sole source of tumor recurrence and are known to be resistant to radiation therapy and don't respond well to chemotherapy.

Now, researchers with the UCLA Department of Radiation Oncology at UCLA's Jonsson Comprehensive Cancer Center report for the first time that radiation treatment -- despite killing half of all tumor cells during every treatment -- transforms other cancer cells into treatment-resistant breast cancer stem cells.

The generation of these breast cancer stem cells counteracts the otherwise highly efficient radiation treatment. If scientists can uncover the mechanisms and prevent this transformation from occurring, radiation treatment for breast cancer could become even more effective, said study senior author Dr. Frank Pajonk, an associate professor of radiation oncology and Jonsson Cancer Center researcher.

"We found that these induced breast cancer stem cells (iBCSC) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells (iPS) in regenerative medicine," said Pajonk, who also is a scientist with the Eli and Edythe Broad Center of Regenerative Medicine at UCLA. "It was remarkable that these breast cancers used the same reprogramming pathways to fight back against the radiation treatment."

The study recently appeared in the early online edition of the peer-reviewed journal Stem Cells.

"Controlling the radiation resistance of breast cancer stem cells and the generation of new iBCSC during radiation treatment may ultimately improve curability and may allow for de-escalation of the total radiation doses currently given to breast cancer patients, thereby reducing acute and long-term adverse effects," the study states.

There are very few breast cancer stem cells in a larger pool of breast cancer cells. In this study, Pajonk and his team eliminated the smaller pool of breast cancer stem cells and then irradiated the remaining breast cancer cells and placed them into mice.

Using a unique imaging system Pajonk and his team developed to visualize cancer stem cells, the researchers were able to observe their initial generation into iBCSC in response to the radiation treatment. The newly generated iBCSC were remarkably similar to breast cancer stem cells found in tumors that had not been irradiated, Pajonk said.

The team also found that the iBCSC had a more than 30-fold increased ability to form tumors compared to the non-irradiated breast cancer cells from which they originated.

Pajonk said that the study unites the competing models of clonal evolution and the hierarchical organization of breast cancers, as it suggests that undisturbed, growing tumors maintain a small number of cancer stem cells. However, if challenged by various stressors that threaten their numbers, including ionizing radiation, the breast cancer cells generate iBCSC that may, together with the surviving cancer stem cells, repopulate the tumor.

"What is really exciting about this study is that it gives us a much more complex understanding of the interaction of radiation with cancer cells that goes far beyond DNA damage and cell killing," Pajonk said. "The study may carry enormous potential to make radiation even better."

Pajonk stressed that breast cancer patients should not be alarmed by the study findings and should continue to undergo radiation if recommended by their oncologists.

"Radiation is an extremely powerful tool in the fight against breast cancer," he said. "If we can uncover the mechanism driving this transformation, we may be able to stop it and make the therapy even more powerful."

This study was funded by the National Cancer Institute, the California Breast Cancer Research Program and the Department of Defense.

Recommend this story on Facebook, Twitter,
and Google +1:

Other bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by University of California, Los Angeles (UCLA), Health Sciences, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Chann Lagadec, Erina Vlashi, Lorenza Della Donna, Carmen Dekmezian and Frank Pajonk. Radiation-induced Reprograming of Breast Cancer Cells. Stem Cells, 10 FEB 2012 DOI: 10.1002/stem.1058

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Continue reading here:
Radiation treatment generates cancer stem cells from less aggressive breast cancer cells, study suggests

To Read More: Radiation treatment generates cancer stem cells from less aggressive breast cancer cells, study suggests
categoriaIPS Cell Therapy commentoComments Off on Radiation treatment generates cancer stem cells from less aggressive breast cancer cells, study suggests | dataFebruary 14th, 2012
Read All

Radiation Treatment Generates Cancer Stem Cells from Less Aggressive Breast Cancer Cells

By raymumme

Newswise — Breast cancer stem cells are thought to be the sole source of tumor recurrence and are known to be resistant to radiation therapy and don’t respond well to chemotherapy.

Now, researchers with the UCLA Department of Radiation Oncology at UCLA’s Jonsson Comprehensive Cancer Center report for the first time that radiation treatment –despite killing half of all tumor cells during every treatment - transforms other cancer cells into treatment-resistant breast cancer stem cells.

The generation of these breast cancer stem cells counteracts the otherwise highly efficient radiation treatment. If scientists can uncover the mechanisms and prevent this transformation from occurring, radiation treatment for breast cancer could become even more effective, said study senior author Dr. Frank Pajonk, an associate professor of radiation oncology and Jonsson Cancer Center researcher.

“We found that these induced breast cancer stem cells (iBCSC) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells (iPS) in regenerative medicine,” said Pajonk, who also is a scientist with the Eli and Edythe Broad Center of Regenerative Medicine at UCLA. “It was remarkable that these breast cancers used the same reprogramming pathways to fight back against the radiation treatment.”

The study appears DATE in the early online edition of the peer-reviewed journal Stem Cells.

“Controlling the radiation resistance of breast cancer stem cells and the generation of new iBCSC during radiation treatment may ultimately improve curability and may allow for de-escalation of the total radiation doses currently given to breast cancer patients, thereby reducing acute and long-term adverse effects,” the study states.

There are very few breast cancer stem cells in a larger pool of breast cancer cells. In this study, Pajonk and his team eliminated the smaller pool of breast cancer stem cells and then irradiated the remaining breast cancer cells and placed them into mice.

Using a unique imaging system Pajonk and his team developed to visualize cancer stem cells, the researchers were able to observe their initial generation into iBCSC in response to the radiation treatment. The newly generated iBCSC were remarkably similar to breast cancer stem cells found in tumors that had not been irradiated, Pajonk said.

The team also found that the iBCSC had a more than 30-fold increased ability to form tumors compared to the non-irradiated breast cancer cells from which they originated.

Pajonk said that the study unites the competing models of clonal evolution and the hierarchical organization of breast cancers, as it suggests that undisturbed, growing tumors maintain a small number of cancer stem cells. However, if challenged by various stressors that threaten their numbers, including ionizing radiation, the breast cancer cells generate iBCSC that may, together with the surviving cancer stem cells, repopulate the tumor.

“What is really exciting about this study is that it gives us a much more complex understanding of the interaction of radiation with cancer cells that goes far beyond DNA damage and cell killing,” Pajonk said. “The study may carry enormous potential to make radiation even better.”

Pajonk stressed that breast cancer patients should not be alarmed by the study findings and should continue to undergo radiation if recommended by their oncologists.

“Radiation is an extremely powerful tool in the fight against breast cancer,” he said. “If we can uncover the mechanism driving this transformation, we may be able to stop it and make the therapy even more powerful.”

This study was funded by the National Cancer Institute, the California Breast Cancer Research Program and the Department of Defense.

UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.

Comment/Share

Continued here:
Radiation Treatment Generates Cancer Stem Cells from Less Aggressive Breast Cancer Cells

To Read More: Radiation Treatment Generates Cancer Stem Cells from Less Aggressive Breast Cancer Cells
categoriaIPS Cell Therapy commentoComments Off on Radiation Treatment Generates Cancer Stem Cells from Less Aggressive Breast Cancer Cells | dataFebruary 14th, 2012
Read All

Radiation treatment transforms breast cancer cells into cancer stem cells

By Sykes24Tracey

Now, researchers with the UCLA Department of Radiation Oncology at UCLA's Jonsson Comprehensive Cancer Center report for the first time that radiation treatment –despite killing half of all tumor cells during every treatment - transforms other cancer cells into treatment-resistant breast cancer stem cells.

The generation of these breast cancer stem cells counteracts the otherwise highly efficient radiation treatment. If scientists can uncover the mechanisms and prevent this transformation from occurring, radiation treatment for breast cancer could become even more effective, said study senior author Dr. Frank Pajonk, an associate professor of radiation oncology and Jonsson Cancer Center researcher.

"We found that these induced breast cancer stem cells (iBCSC) were generated by radiation-induced activation of the same cellular pathways used to reprogram normal cells into induced pluripotent stem cells (iPS) in regenerative medicine," said Pajonk, who also is a scientist with the Eli and Edythe Broad Center of Regenerative Medicine at UCLA. "It was remarkable that these breast cancers used the same reprogramming pathways to fight back against the radiation treatment."

The study appears DATE in the early online edition of the peer-reviewed journal Stem Cells.

"Controlling the radiation resistance of breast cancer stem cells and the generation of new iBCSC during radiation treatment may ultimately improve curability and may allow for de-escalation of the total radiation doses currently given to breast cancer patients, thereby reducing acute and long-term adverse effects," the study states.

There are very few breast cancer stem cells in a larger pool of breast cancer cells. In this study, Pajonk and his team eliminated the smaller pool of breast cancer stem cells and then irradiated the remaining breast cancer cells and placed them into mice.

Using a unique imaging system Pajonk and his team developed to visualize cancer stem cells, the researchers were able to observe their initial generation into iBCSC in response to the radiation treatment. The newly generated iBCSC were remarkably similar to breast cancer stem cells found in tumors that had not been irradiated, Pajonk said.

The team also found that the iBCSC had a more than 30-fold increased ability to form tumors compared to the non-irradiated breast cancer cells from which they originated.

Pajonk said that the study unites the competing models of clonal evolution and the hierarchical organization of breast cancers, as it suggests that undisturbed, growing tumors maintain a small number of cancer stem cells. However, if challenged by various stressors that threaten their numbers, including ionizing radiation, the breast cancer cells generate iBCSC that may, together with the surviving cancer stem cells, repopulate the tumor.

"What is really exciting about this study is that it gives us a much more complex understanding of the interaction of radiation with cancer cells that goes far beyond DNA damage and cell killing," Pajonk said. "The study may carry enormous potential to make radiation even better."

Pajonk stressed that breast cancer patients should not be alarmed by the study findings and should continue to undergo radiation if recommended by their oncologists.

"Radiation is an extremely powerful tool in the fight against breast cancer," he said. "If we can uncover the mechanism driving this transformation, we may be able to stop it and make the therapy even more powerful."

Provided by University of California - Los Angeles

Read more here:
Radiation treatment transforms breast cancer cells into cancer stem cells

To Read More: Radiation treatment transforms breast cancer cells into cancer stem cells
categoriaIPS Cell Therapy commentoComments Off on Radiation treatment transforms breast cancer cells into cancer stem cells | dataFebruary 14th, 2012
Read All

“Wide-ranging applications for pluripotent stem cells”

By JoanneRUSSELL25

The Hindu Shinya Yamanaka, Centre for iPS Cell Research and Application, Japan delivering a lecture in Chennai on Thursday. Photo: V. Ganesan

Many more diseases can be targeted, says expert

While applications of induced pluripotent stem cells in stem cell therapy may be limited to a few diseases, its applications in drug discovery are wide-ranging, and many more diseases can be targeted, Shinya Yamanaka, Director, Centre for iPS Cell Research and Application, Japan, has said.

The Japanese scientist, whose breakthrough was the creation of embryonic-like stem cells from adult skin cells, believes that the best chance for stem cell therapy lies in offering hope to those suffering from a few conditions, among them, macular disease, Type 1 Diabetes, and spinal cord injuries.

On the other hand, there were multiple possibilities with drug discovery for a range of diseases, and Prof. Yamanaka was hopeful that more scientists would continue to use iPS for studying this potential.

He currently serves as the Director of the Center for iPS Cell Research and Application and as Professor at the Institute for Frontier Medical Sciences at Kyoto University. He is also a Senior Investigator at the University of California, San Francisco (UCSF) - affiliated J. David Gladstone Institutes.

An invited speaker of the CellPress-TNQ India Distinguished Lectureship Series, co-sponsored by Cell Press and TNQ Books and Journals, Prof. Yamanaka spoke to a Chennai audience on Tuesday evening about those “immortal” cells, that he originally thought would take “forever” to create, but actually took only six years.

“My fixed vision for my research team was to re-programme adult cells to function like embryonic-like stem cells. I knew it could be done, but just didn't know how to do it,” Prof. Yamanaka said.

Embryonic stem cells are important because they are pluripotent, or possess the ability to differentiate into any other type of cell, and are capable of rapid proliferation. However, despite the immense possibilities of that, embryonic cells are a mixed blessing: there are issues with post-transplant rejection (since they cannot be used from a patient's own cells), and many countries of the world do not allow the use of human embryos.

Dr. Yamanaka's solution would scale these challenges if only he and his team could find a way to endow non-embryonic cells with those two key characteristics of embryonic stem cells.

In 2006, he and his team of young researchers — Yoshimi Tokuzawa, Kazutoshi Takahashi and Tomoko Ishisaka — were able to show that by introducing four factors into mouse skin cells, it was possible to generate ES-like mouse cells. The next year, they followed up that achievement, replicating the same strategy and converted human skin cells into iPS cells. “All we need is a small sample of skin (2-3millimetres) from the patient. This will be used to generate skin fibroblasts, and adding the factors, they can be converted to iPS cells. These cells can make any type of cell, including beating cardiac myocytes (heart cells), Prof.Yamanaka explained.

iPS cells hold out for humanity a lot of hope in curing diseases that have a single cell cause. Prominent among them are Lou Gehrig's Disease or Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease. Motor neurons degenerate and die, and no effective treatment exists thus far. One reason is that there have not been good disease models for ALS in humans. It is difficult to get motor neuron from human patients and motor neurons cannot divide.

“Now, iPS cells can proliferate and can be differentiated to make motor neurons in large numbers,” he explained. Already a scientist in Japan has clarified motor neuron cells from iPS. “We are hoping that in the near future we would be able to evolve drug candidates that will be useful for ALS patients.” Treatment of spinal cord injuries using iPS cells has showed good results in mice and monkey specimens, and it is likely that in two or three years, scientists will be ready to start treatment for humans.

Toxicology, or drug side effects, is another area where iPS cells can be of use. Testing drug candidates directly on patients can be extremely dangerous. However, iPS cells can be differentiated into the requisite cell type, and the drugs tested on them for reactions. And yet, as wonderful as they may seem, iPS cells do have drawbacks, and there are multiple challenges to be faced before the technology can be applied to medicine. Are they equivalent and indistinguishable from ES cells? For a technology that has been around for only five years, the questions remain about safety. Also to derive patient-specific iPS cells, the process is time, and money-consuming, Prof. Yamanaka pointed out.

There are however, solutions in the offing, for the man who made the world's jaw drop with his discovery. One would be to create an iPS cell bank, where iPS cells could be created in advance from healthy volunteers donating peripheral blood, and skin fibroblasts, apart from frozen cord blood. The process of setting a rigorous quality control mechanism to select the best and safest iPS clones is on and would be complete within a year or two. “Many scientists are studying iPS cells across the world, and I'm optimistic that because of these efforts, we can overcome the challenges of iPS, and contribute to newer treatments for intractable diseases,” Prof. Yamanaka said.

N. Ram, Director, Kasturi & Sons Limited, introduced the speaker. Mariam Ram, managing director, TNQ India; and Emilie Marcus, executive editor, Cell Press, spoke.

Follow this link:
“Wide-ranging applications for pluripotent stem cells”

To Read More: “Wide-ranging applications for pluripotent stem cells”
categoriaIPS Cell Therapy commentoComments Off on “Wide-ranging applications for pluripotent stem cells” | dataFebruary 2nd, 2012
Read All

Researchers turn skin cells into neural precusors, bypassing stem-cell stage

By JoanneRUSSELL25

The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called "induced pluripotency" could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new study, which will be published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory — a feature critical for their long-term usefulness in transplantation or drug screening.

In the study, the switch from skin to neural precursor cells occurred with high efficiency over a period of about three weeks after the addition of just three transcription factors. (In the previous study, a different combination of three transcription factors was used to generate mature neurons.) The finding implies that it may one day be possible to generate a variety of neural-system cells for transplantation that would perfectly match a human patient.

"We are thrilled about the prospects for potential medical use of these cells," said Marius Wernig, MD, assistant professor of pathology and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. "We've shown the cells can integrate into a mouse brain and produce a missing protein important for the conduction of electrical signal by the neurons. This is important because the mouse model we used mimics that of a human genetic brain disease. However, more work needs to be done to generate similar cells from human skin cells and assess their safety and efficacy."

Wernig is the senior author of the research. Graduate student Ernesto Lujan is the first author.

While much research has been devoted to harnessing the pluripotency of embryonic stem cells, taking those cells from an embryo and then implanting them in a patient could prove difficult because they would not match genetically. An alternative technique involves a concept called induced pluripotency, first described in 2006. In this approach, transcription factors are added to specialized cells like those found in skin to first drive them back along the developmental timeline to an undifferentiated stem-cell-like state. These "iPS cells" are then grown under a variety of conditions to induce them to re-specialize into many different cell types.

Scientists had thought that it was necessary for a cell to first enter an induced pluripotent state or for researchers to start with an embryonic stem cell, which is pluripotent by nature, before it could go on to become a new cell type. However, research from Wernig's laboratory in early 2010 showed that it was possible to directly convert one "adult" cell type to another with the application of specialized transcription factors, a process known as transdifferentiation.

Wernig and his colleagues first converted skin cells from an adult mouse to functional neurons (which they termed induced neuronal, or iN, cells), and then replicated the feat with human cells. In 2011 they showed that they could also directly convert liver cells into iN cells.

"Dr. Wernig's demonstration that fibroblasts can be converted into functional nerve cells opens the door to consider new ways to regenerate damaged neurons using cells surrounding the area of injury," said pediatric cardiologist Deepak Srivastava, MD, who was not involved in these studies. "It also suggests that we may be able to transdifferentiate cells into other cell types." Srivastava is the director of cardiovascular research at the Gladstone Institutes at the University of California-San Francisco. In 2010, Srivastava transdifferentiated mouse heart fibroblasts into beating heart muscle cells.

"Direct conversion has a number of advantages," said Lujan. "It occurs with relatively high efficiency and it generates a fairly homogenous population of cells. In contrast, cells derived from iPS cells must be carefully screened to eliminate any remaining pluripotent cells or cells that can differentiate into different lineages." Pluripotent cells can cause cancers when transplanted into animals or humans.

The lab's previous success converting skin cells into neurons spurred Wernig and Lujan to see if they could also generate the more-versatile neural precursor cells, or NPCs. To do so, they infected embryonic mouse skin cells — a commonly used laboratory cell line — with a virus encoding 11 transcription factors known to be expressed at high levels in NPCs. A little more than three weeks later, they saw that about 10 percent of the cells had begun to look and act like NPCs.

Repeated experiments allowed them to winnow the original panel of 11 transcription factors to just three: Brn2, Sox2 and FoxG1. (In contrast, the conversion of skin cells directly to functional neurons requires the transcription factors Brn2, Ascl1 and Myt1l.) Skin cells expressing these three transcription factors became neural precursor cells that were able to differentiate into not just neurons and astrocytes, but also oligodendrocytes, which make the myelin that insulates nerve fibers and allows them to transmit signals. The scientists dubbed the newly converted population "induced neural precursor cells," or iNPCs.

In addition to confirming that the astrocytes, neurons and oligodendrocytes were expressing the appropriate genes and that they resembled their naturally derived peers in both shape and function when grown in the laboratory, the researchers wanted to know how the iNPCs would react when transplanted into an animal. They injected them into the brains of newborn laboratory mice bred to lack the ability to myelinate neurons. After 10 weeks, Lujan found that the cells had differentiated into oligodendroytes and had begun to coat the animals' neurons with myelin.

"Not only do these cells appear functional in the laboratory, they also seem to be able to integrate appropriately in an in vivo animal model," said Lujan.

The scientists are now working to replicate the work with skin cells from adult mice and humans, but Lujan emphasized that much more research is needed before any human transplantation experiments could be conducted. In the meantime, however, the ability to quickly and efficiently generate neural precursor cells that can be grown in the laboratory to mass quantities and maintained over time will be valuable in disease and drug-targeting studies.

"In addition to direct therapeutic application, these cells may be very useful to study human diseases in a laboratory dish or even following transplantation into a developing rodent brain," said Wernig.

Provided by Stanford University Medical Center (news : web)

See the article here:
Researchers turn skin cells into neural precusors, bypassing stem-cell stage

To Read More: Researchers turn skin cells into neural precusors, bypassing stem-cell stage
categoriaIPS Cell Therapy commentoComments Off on Researchers turn skin cells into neural precusors, bypassing stem-cell stage | dataJanuary 31st, 2012
Read All

Stanford scientists turn skin cells into neural precusors, bypassing stem-cell stage

By Dr. Matthew Watson

Public release date: 30-Jan-2012
[ | E-mail | Share ]

Contact: Krista Conger
kristac@stanford.edu
650-725-5371
Stanford University Medical Center

STANFORD, Calif. ? Mouse skin cells can be converted directly into cells that become the three main parts of the nervous system, according to researchers at the Stanford University School of Medicine. The finding is an extension of a previous study by the same group showing that mouse and human skin cells can be directly converted into functional neurons.

The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called "induced pluripotency" could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new study, which will be published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory ? a feature critical for their long-term usefulness in transplantation or drug screening.

In the study, the switch from skin to neural precursor cells occurred with high efficiency over a period of about three weeks after the addition of just three transcription factors. (In the previous study, a different combination of three transcription factors was used to generate mature neurons.) The finding implies that it may one day be possible to generate a variety of neural-system cells for transplantation that would perfectly match a human patient.

"We are thrilled about the prospects for potential medical use of these cells," said Marius Wernig, MD, assistant professor of pathology and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. "We've shown the cells can integrate into a mouse brain and produce a missing protein important for the conduction of electrical signal by the neurons. This is important because the mouse model we used mimics that of a human genetic brain disease. However, more work needs to be done to generate similar cells from human skin cells and assess their safety and efficacy."

Wernig is the senior author of the research. Graduate student Ernesto Lujan is the first author.

While much research has been devoted to harnessing the pluripotency of embryonic stem cells, taking those cells from an embryo and then implanting them in a patient could prove difficult because they would not match genetically. An alternative technique involves a concept called induced pluripotency, first described in 2006. In this approach, transcription factors are added to specialized cells like those found in skin to first drive them back along the developmental timeline to an undifferentiated stem-cell-like state. These "iPS cells" are then grown under a variety of conditions to induce them to re-specialize into many different cell types.

Scientists had thought that it was necessary for a cell to first enter an induced pluripotent state or for researchers to start with an embryonic stem cell, which is pluripotent by nature, before it could go on to become a new cell type. However, research from Wernig's laboratory in early 2010 showed that it was possible to directly convert one "adult" cell type to another with the application of specialized transcription factors, a process known as transdifferentiation.

Wernig and his colleagues first converted skin cells from an adult mouse to functional neurons (which they termed induced neuronal, or iN, cells), and then replicated the feat with human cells. In 2011 they showed that they could also directly convert liver cells into iN cells.

"Dr. Wernig's demonstration that fibroblasts can be converted into functional nerve cells opens the door to consider new ways to regenerate damaged neurons using cells surrounding the area of injury," said pediatric cardiologist Deepak Srivastava, MD, who was not involved in these studies. "It also suggests that we may be able to transdifferentiate cells into other cell types." Srivastava is the director of cardiovascular research at the Gladstone Institutes at the University of California-San Francisco. In 2010, Srivastava transdifferentiated mouse heart fibroblasts into beating heart muscle cells.

"Direct conversion has a number of advantages," said Lujan. "It occurs with relatively high efficiency and it generates a fairly homogenous population of cells. In contrast, cells derived from iPS cells must be carefully screened to eliminate any remaining pluripotent cells or cells that can differentiate into different lineages." Pluripotent cells can cause cancers when transplanted into animals or humans.

The lab's previous success converting skin cells into neurons spurred Wernig and Lujan to see if they could also generate the more-versatile neural precursor cells, or NPCs. To do so, they infected embryonic mouse skin cells ? a commonly used laboratory cell line ? with a virus encoding 11 transcription factors known to be expressed at high levels in NPCs. A little more than three weeks later, they saw that about 10 percent of the cells had begun to look and act like NPCs.

Repeated experiments allowed them to winnow the original panel of 11 transcription factors to just three: Brn2, Sox2 and FoxG1. (In contrast, the conversion of skin cells directly to functional neurons requires the transcription factors Brn2, Ascl1 and Myt1l.) Skin cells expressing these three transcription factors became neural precursor cells that were able to differentiate into not just neurons and astrocytes, but also oligodendrocytes, which make the myelin that insulates nerve fibers and allows them to transmit signals. The scientists dubbed the newly converted population "induced neural precursor cells," or iNPCs.

In addition to confirming that the astrocytes, neurons and oligodendrocytes were expressing the appropriate genes and that they resembled their naturally derived peers in both shape and function when grown in the laboratory, the researchers wanted to know how the iNPCs would react when transplanted into an animal. They injected them into the brains of newborn laboratory mice bred to lack the ability to myelinate neurons. After 10 weeks, Lujan found that the cells had differentiated into oligodendroytes and had begun to coat the animals' neurons with myelin.

"Not only do these cells appear functional in the laboratory, they also seem to be able to integrate appropriately in an in vivo animal model," said Lujan.

The scientists are now working to replicate the work with skin cells from adult mice and humans, but Lujan emphasized that much more research is needed before any human transplantation experiments could be conducted. In the meantime, however, the ability to quickly and efficiently generate neural precursor cells that can be grown in the laboratory to mass quantities and maintained over time will be valuable in disease and drug-targeting studies.

"In addition to direct therapeutic application, these cells may be very useful to study human diseases in a laboratory dish or even following transplantation into a developing rodent brain," said Wernig.

###

In addition to Wernig and Lujan, other Stanford researchers involved in the study include postdoctoral scholars Soham Chanda, PhD, and Henrik Ahlenius, PhD; and professor of molecular and cellular physiology Thomas Sudhof, MD.

The research was supported by the California Institute for Regenerative Medicine, the New York Stem Cell Foundation, the Ellison Medical Foundation, the Stinehart-Reed Foundation and the National Institutes of Health.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital andamp; Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

PRINT MEDIA CONTACT: Krista Conger at (650) 725-5371 (kristac@stanford.edu)
BROADCAST MEDIA CONTACT: M.A. Malone at (650) 723-6912 (mamalone@stanford.edu)

[ | E-mail | Share ]

andnbsp;

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Read more here:
Stanford scientists turn skin cells into neural precusors, bypassing stem-cell stage

To Read More: Stanford scientists turn skin cells into neural precusors, bypassing stem-cell stage
categoriaIPS Cell Therapy commentoComments Off on Stanford scientists turn skin cells into neural precusors, bypassing stem-cell stage | dataJanuary 31st, 2012
Read All

Professor Alan Trounson – World focus on stem cell research – Video

By Sykes24Tracey

19-01-2012 22:48 Stem cell research has the potential to yield groundbreaking new tools to understand and develop therapies for CP and related brain disorders.

Here is the original post:
Professor Alan Trounson - World focus on stem cell research - Video

To Read More: Professor Alan Trounson – World focus on stem cell research – Video
categoriaIPS Cell Therapy commentoComments Off on Professor Alan Trounson – World focus on stem cell research – Video | dataJanuary 27th, 2012
Read All

Parkinson’s Disease: Advancing Stem Cell Therapies – 2011 CIRM Grantee Meeting – Video

By daniellenierenberg

09-11-2011 14:00 Olga Momcilovic speaks at the 2011 CIRM Grantee Meeting about the use of induced pluripotent stem (iPS) cells to better understand the causes of Parkinson's and to develop therapies. Momcilovic is a CIRM Scholar and postdoctoral research fellow at the Buck Institute located in Novato, California.

Read more here:
Parkinson's Disease: Advancing Stem Cell Therapies - 2011 CIRM Grantee Meeting - Video

To Read More: Parkinson’s Disease: Advancing Stem Cell Therapies – 2011 CIRM Grantee Meeting – Video
categoriaIPS Cell Therapy commentoComments Off on Parkinson’s Disease: Advancing Stem Cell Therapies – 2011 CIRM Grantee Meeting – Video | dataJanuary 20th, 2012
Read All

2011 Summit: Stem Cells, Reprogramming and Personalized Medicine, Rudolf Jaenisch, MD – Video

By daniellenierenberg

Rudolf Jaenisch, MD (MIT) and recently named winner of the National Medal of Science, discussed the key issues facing the field of highly pluripotent stem cells including ES cells and iPS cells.

View post:
2011 Summit: Stem Cells, Reprogramming and Personalized Medicine, Rudolf Jaenisch, MD - Video

To Read More: 2011 Summit: Stem Cells, Reprogramming and Personalized Medicine, Rudolf Jaenisch, MD – Video
categoriaIPS Cell Therapy commentoComments Off on 2011 Summit: Stem Cells, Reprogramming and Personalized Medicine, Rudolf Jaenisch, MD – Video | dataDecember 14th, 2011
Read All

Advances in Stem Cell Research: Shinya Yamanaka – Video

By JoanneRUSSELL25

Interviews with Deepak Srivastava, Shinya Yamanaka and Robert Mahley on Dr. Yamanaka's discovery and future directions in stem cell research.

Read the rest here:
Advances in Stem Cell Research: Shinya Yamanaka - Video

To Read More: Advances in Stem Cell Research: Shinya Yamanaka – Video
categoriaIPS Cell Therapy commentoComments Off on Advances in Stem Cell Research: Shinya Yamanaka – Video | dataDecember 11th, 2011
Read All

Jeff Bluestone: Immune rejection of stem cell transplants – Video

By Sykes24Tracey

Any cells derived from embryonic stem cells that are transplanted as a therapy will likely be rejected by the immune system much like a transplanted heart or liver. Dr. Jeffrey Bluestone has been studying ways of achieving transplantation with little or no drugs.

Follow this link:
Jeff Bluestone: Immune rejection of stem cell transplants - Video

To Read More: Jeff Bluestone: Immune rejection of stem cell transplants – Video
categoriaIPS Cell Therapy commentoComments Off on Jeff Bluestone: Immune rejection of stem cell transplants – Video | dataDecember 8th, 2011
Read All

Ian Wilmut discusses stem cell and direct cellular transformation therapy – Video

By daniellenierenberg

Ian Wilmut discusses stem cell and direct cellular transformation therapy at the 2011 Stem Cell Meeting on the Mesa at the Salk Institute, Nov.

Read more:
Ian Wilmut discusses stem cell and direct cellular transformation therapy - Video

To Read More: Ian Wilmut discusses stem cell and direct cellular transformation therapy – Video
categoriaIPS Cell Therapy commentoComments Off on Ian Wilmut discusses stem cell and direct cellular transformation therapy – Video | dataDecember 8th, 2011
Read All

Page 22«..10..21222324


Copyright :: 2024