Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

UCSF Scientists Use Human Stem Cells to Generate Immune System in Mice

Published: Friday, May 17, 2013
Last Updated: Friday, May 17, 2013
Bookmark and Share
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory.

The researchers showed that, in mice, the tissue can be used to foster the development of white blood cells the body needs to mount healthy immune responses and to prevent harmful autoimmune reactions.

The scientists who developed the thymus cells — which caused the proliferation and maturation of functioning immune cells when transplanted — said the achievement marks a significant step toward potential new treatments based on stem-cell and organ transplantation, as well as new therapies for type-1 diabetes and other autoimmune diseases, and for immunodeficiency diseases.

Starting with human embryonic stem cells, UCSF researchers led by Mark Anderson, MD, PhD, an immunologist, and Matthias Hebrok, PhD, a stem-cell researcher and the director of the UCSF Diabetes Center, used a unique combination of growth factors to shape the developmental trajectory of the cells, and eventually hit upon a formula that yielded functional thymus tissue.

The result, reported in the May 16, 2013 online edition of the journal Cell Stem Cell, is functioning tissue that nurtures the growth and development of the white blood cells known as T cells. T cells are a central immune cell population that responds to specific disease pathogens and also prevents the immune system from attacking the body’s own tissues.

Thymus May Be Obscure, But Not Expendable

The thymus might be a bit obscure to the layperson — it’s a small gland at the top of the chest beneath the breastbone — but it is in no way expendable, as individuals with defective thymus function succumb to infection early in life.

Given the invasive nature of cell therapy, which remains completely experimental, the first treatments using laboratory-derived thymus tissue would likely be studied in patients with fatal diseases for which there are no effective treatments, Anderson said. For example, one early treatment might be for the genetic disease DeGeorge syndrome, in which some newborns are born without a thymus gland and die in infancy.

However, a potentially greater impact may be in the area of tissue transplantation, a goal of the emerging field of stem-cell-based therapies. Stem-cell-based therapies now are limited by the potential for the immune system to reject transplanted stem cells, Anderson said. For transplantation, stem cells might be coaxed down two developmental pathways simultaneously, to form both thymus tissue and a replacement organ. Transplantation of both might overcome the rejection barrier without the need for harmful immunosuppression, according to Anderson.

“The thymus is an environment in which T cells mature, and where they also are instructed on the difference between self and non-self,” Anderson said. Some T cells are prepared by the thymus to attack foreign invaders — including transplants, while T cells that would attack our own tissues normally are eliminated in the thymus.

In the same vein, thymus tissue might one day be used to retrain the immune system in autoimmune diseases, in which the immune system abnormally attacks “self,” thereby enhancing recognition and protecting from immune destruction.

Researchers have discovered many of the proteins and growth factors that are switched on during the course of embryonic development and that are crucial to organ formation. Hebrok has spent years trying to develop insulin-secreting beta cells, a part of the pancreas that is destroyed during the course of diabetes.

The sequential appearance of specific marker proteins within cells as they develop into the distinct organs of the gastrointestinal tract serves as a series of milestones, which has helped orient Hebrok and others as they seek to guide the formation of distinct tissues.

Hebrok likens the quest for organ specific cells, including thymus cells and the elusive pancreatic beta cell, to an adventurous road trip. The pancreas and the thymus branch off the gastrointestinal tract in different places, but they share certain developmental markers.

To get to thymus cells, the researchers tried dozens of protocols, timing the switching on of the key factors differently each time. “If we used one factor for a day longer or shorter it would not work,” Hebrok said. With the milestones misplaced, “It would be like driving down the highway and missing your exit.”

The researchers caution that they have not perfectly replicated the thymus, and that only about 15 percent of cells are successfully directed to become thymus tissue with the protocol used in the study.

Even so, Anderson said, “We now have developed a tool that allows us to modulate the immune system in a manner that we never had before.”

Additional study authors include UCSF Diabetes Center postdoctoral fellows Audrey Parent, PhD, Holger Russ, PhD; and graduate students Imran Khan, Taylor LaFlam, and Todd Metzger.

The research was funded by the California Institute for Regenerative Medicine and by the National Institutes of Health. Mark Anderson is the Robert B. Friend and Michelle M. Friend Professor in Diabetes Research at UCSF, and Matthias Hebrok is the Hurlbut-Johnson Distinguished Professor in Diabetes Research. Hebrok and Anderson have founded a company, ThyGen Inc., to advance the discoveries described in Cell Stem Cell.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Growing Spinal Disc Tissue
Scientists develop new method for growing spinal disc tissue in the lab for combating chronic back pain.
Friday, July 03, 2015
Grant Supports Creation of Patient-Derived Stem Cell Lines
Researchers have received a two-year, $600,000 grant from the National Institute on Aging to develop and study patient-derived stem cell lines.
Thursday, December 12, 2013
Prostate Cancer Stem Cells are a Moving Target
Researchers have discovered how prostate cancer stem cells evolve as the disease progresses, a finding that could help point the way to more highly targeted therapies.
Friday, December 06, 2013
Researchers Change Cell Types by Flipping a Single Switch
New findings have identified a method for changing one cell type into another in a process called forced transdifferentiation.
Friday, December 06, 2013
Understanding a Protein’s Role in Familial Alzheimer’s
Researchers have used genetic engineering of human iPSC’s to specifically and precisely parse the roles of a key mutated protein in causing familial Alzheimer's disease (AD).
Monday, November 18, 2013
Researchers Un-Junking Junk DNA
A study shines a new light on molecular tools our cells use to govern regulated gene expression.
Wednesday, November 13, 2013
$100M gift launches Sanford Stem Cell Clinical Center
T. Denny Sanford has committed $100 million to the creation of the Sanford Stem Cell Clinical Center at the University of California, San Diego.
Wednesday, November 06, 2013
Grafted Limb Cells Acquire Molecular ‘Fingerprint’ of New Location
Findings further creation of regenerative therapies for humans.
Wednesday, October 30, 2013
From Mature Cells to Embryonic-Like Stem Cells
Bioengineers have shown that physical cues can replace certain chemicals when nudging mature cells back to a pluripotent stage.
Tuesday, October 22, 2013
Researchers Develop Stem Cell Therapies for Acute Lung Injury
An estimated 200,000 patients a year have acute respiratory failure in the U.S. and mortality is about 30 to 40 percent.
Monday, October 21, 2013
Single Gene Mutation Linked to Neurological Disorders
Mutation could offer insights into Alzheimer’s, Parkinson’s and Huntigton’s Diseases.
Wednesday, October 16, 2013
Gene Repair Technique Could Have Many Applications
Using human pluripotent stem cells and DNA-cutting protein from meningitis bacteria, researchers have created an efficient way to target and repair defective genes.
Tuesday, August 13, 2013
Therapy Could Treat Breast Cancer that's Spread to Brain
Researchers have successfully combined cellular therapy and gene therapy in a mouse-model system to develop a viable treatment strategy for breast cancer that has spread to a patient's brain.
Tuesday, August 06, 2013
Scientists Streamline Production of Stem Cells
Researchers report a simple, easily reproducible RNA-based method of generating human induced pluripotent stem cells (iPSCs).
Friday, August 02, 2013
Scientific News
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
New Material Forges the Way for 'Stem Cell Factories'
Researchers have discovered the first fully synthetic substrate with potential to grow billions of stem cells. The researchcould forge the way for the creation of 'stem cell factories' - the mass production of human embryonic (pluripotent) stem cells.
Liver Regrown from Stem Cells
Scientists have repaired a damaged liver in a mouse by transplanting stem cells grown in the laboratory.
Immunotherapy Shows Promise for Myeloma
A strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
'Google Maps' for the Body
Scientists have revealed research that uses previously top-secret technology to zoom through the human body down to the level of a single cell that could be a game-changer for medicine.
Adaptimmune's Novel Cancer Therapeutics Show Positive Clinical Trial Results
The company has announced that positive data from its Phase I/II study of its affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen in patients with multiple myeloma has been published.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!