Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Biologists Discover Solution to Problem Limiting Development of Human Stem Cell Therapies

Published: Tuesday, January 07, 2014
Last Updated: Tuesday, January 07, 2014
Bookmark and Share
An effective strategy that could prevent the human immune system from rejecting the hESCs derived grafts.

Biologists at UC San Diego have discovered an effective strategy that could prevent the human immune system from rejecting the grafts derived from human embryonic stem cells, a major problem now limiting the development of human stem cell therapies.

Their discovery may also provide scientists with a better understanding of how tumors evade the human immune system when they spread throughout the body.

The achievement, published in a paper in this week’s early online edition of the journal Cell Stem Cell by a collaboration that included scientists from China, was enabled by the development of “humanized” laboratory mice that contained a functional human immune system capable of mounting a vigorous immune rejection of foreign cells derived from human embryonic stem cells.

Because human embryonic stem cells are different from our own body’s cells, or “allogenic,” a normally functioning human immune system will attack these foreign cells. One way to reduce the body’s “allogenic immune response” is to suppress the immune system with immunosuppressant drugs.

“For organ transplantation to save patients with terminal diseases that has been quite successful,” says Yang Xu, a professor of biology who headed the team of researchers that included Ananda Goldrath, an associate biology professor at UC San Diego. “But for stem cell therapies, the long term use of toxic immunosuppressant drugs for patients who are being treated for chronic diseases like Parkinson’s disease or diabetes pose serious health problems.”

Researchers had long been searching for a human immunity relevant model that would allow them to develop strategies to implant allogenic cells derived from embryonic stem cells safely. “The problem is that we only had data from mouse immune system and those are not usually translatable in humans, because human and mouse immune systems are quite different,” explains Xu. “So what we decided to do was to optimize the humanized mouse that carries a functional human immune system.”

To do that, the biologists took immune deficient laboratory mice and grafted into their bodies human fetal thymus tissues and hematopoietic stem cells derived from fetal liver of the same human donor. “That reconstituted in these mice a normally functioning human immune system that effectively rejects cells derived human embryonic stem cells,” says Xu. With these “humanized” mouse models, the biologists then tested a variety of immune suppressing molecules alone or in combination and discovered one combination that worked perfectly to protect cells derived from human embryonic stem cells from immune rejection.

That combination was CTLA4-lg, an FDA-approved drug for treating rheumatoid arthritis that suppresses T-cells responsible for immune rejection, and a protein called PD-L1 known to be important for inducing immune tolerance in tumors. The researchers discovered that the combination of these two molecules allowed the allogeneic cells to survive in humanized mice without triggering an immune rejection.

“If we express both molecules in cells derived from human embryonic cells, we can protect these cells from the allogenic immune rejection,” says Xu. “If you have only one such molecule expressed, there is absolutely no impact. We still don’t know exactly how these pathways work together to suppress immune rejection, but now we’ve got an ideal system to study this.”

He and his team of researchers also believe their discovery and the development of their humanized mouse models may offer the much needed tools to develop ways to activate immune response to tumors, because these molecules are known to be important in allowing tumors to evade the human immune system.

“You’re dealing with the same exact pathways that protect tumors from our immune system,” says Xu. “If we can develop strategies to disrupt or silence these pathways in tumors, we might be able to activate immunity to tumors. The humanized mouse system is really a powerful model with which to study human tumor immunity.”


Further Information

Join For Free

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 3,300+ scientific posters on ePosters
  • More Than 4,900+ 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

Magnetic Drug Delivery in the Body
Imagine a device that could transport drugs to any diseased site in the body with the help of a small magnet.
Wednesday, August 10, 2016
Body’s Own Gene Editing System Generates Leukemia Stem Cells
Inhibiting the editing enzyme may provide a new therapeutic approach for blood cancers.
Friday, June 10, 2016
Slime Mold Reveals Clues to Immune Cells’ Directional Abilities
Study from UC San Diego identifies a protein involved in the directional ability of a slime mold.
Friday, May 27, 2016
New Technology is Life-Saving Voice for Premature Infants
Innovative monitoring system detects risk of infections up to 24 hours before symptoms appear.
Wednesday, May 11, 2016
Uncovering Hidden Genomic Alterations that Drive Cancers
Tested on large tumor genomics database, REVEALER method allows researchers to connect genomics to cell function.
Tuesday, April 19, 2016
Stem Cells Regenerate Damage in Corticospinal Injury
For the first time, researchers show functional benefit in animal model of key motor control system.
Friday, April 01, 2016
New Method Identifies Up to Twice as Many Proteins and Peptides
An international team of researchers developed a method that identifies up to twice as many proteins and peptides in mass spectrometry data than conventional approaches.
Thursday, November 19, 2015
Tiny Parasite May Have Big Impact on Honey Bees
Biologists at UC San Diego have discovered that a tiny single-celled parasite may have a greater-than expected impact on honey bee colonies.
Monday, June 01, 2015
Blood-Based Genetic Biomarkers Identify Young Boys with Autism
Proof-of-principle method suggests much-earlier diagnoses could be done with clinic test.
Wednesday, March 11, 2015
Anti-Leukemia Drug May Also Work Against Ovarian Cancer
An antibody therapy already in clinical trials to treat chronic lymphocytic leukemia (CLL) may also prove effective against ovarian cancer – and likely other cancers as well.
Wednesday, November 19, 2014
New Blood: Tracing the Beginnings of Hematopoietic Stem Cells
Researchers uncover earliest clues yet to development of cells that produce all adult blood cells.
Monday, August 18, 2014
New Reprogramming Method Makes Better Stem Cells
Researchers have shown for the first time that stem cells created using different methods produce differing cells.
Friday, July 04, 2014
Biologists Find ‘Missing Link’ in the Production of Protein Factories in Cells
Biologists at UC San Diego have found the “missing link” in the chemical system that enables animal cells to produce ribosomes.
Tuesday, June 24, 2014
Researchers Develop Efficient Model for Generating Human Stem Cells
Approach has potential to simplify generation of iPSCs for use in human stem cell therapies.
Wednesday, August 07, 2013
In Vitro Study Finds Digested Formula, But Not Breast Milk, is Toxic to Cells
Findings may help explain development of fatal condition in premature infants.
Wednesday, January 09, 2013
Scientific News
Shedding Light on HIV Vaccine Design
Broadly speaking - Mathematical modelling of host-pathogen coevolution sheds light on HIV vaccine design.
AACC 2016 Sees Clinical Chemistry Labs Drive Precision Medicine Offerings
Biomarker assays to enable precision medicine and risk assessment, mass spec-based tests designed for use in clinical labs large and small, and liquid biopsy technology captured the spotlight at the AACC annual meeting.
Automated Patch Clamping Trends
Learn more about current practices, preferences and metrics in ion channel drug screening using APC technology.
Lab-on-a-Stick: Miniaturised Clinical Testing For Fast Detection Of Antibiotic Resistance
A portable power-free test for the rapid detection of bacterial resistance to antibiotics has been developed by academics at Loughborough University and the University of Reading.
Genetic Ancestry of Cultivated Strawberry Unravelled
UNH scientists constructed a linkage map of the seven chromosomes of the diploid Fragaria iinumae, which allows them to fill in a piece of the genetic puzzle about the eight sets of chromosomes of the cultivated strawberry.
Progress In Vaccination Against Vespid Venom
Researchers at the Helmholtz Zentrum München and the Technical University Munich have presented a method which facilitates a personalised procedure for wasp allergy sufferers.
New Drug Target for Inflammatory Disorders
Penn study finds enigmatic molecules maintain equilibrium between fighting infection and inflammatory havoc.
Breast Cancer Cells Found To Switch Molecular Characteristics
Spontaneous interconversion between HER2-positive and HER2-negative states could contribute to progression, treatment resistance in breast cancer.
Mechanisms of Calcium Blockers
Researchers describe how the fundamental mode of action of two distinct chemical classes of calcium channel blockers differs.
Some Breast Cancer Patients With Low Genetic Risk Could Skip Chemotherapy
Genetic test can help predict survival and guide treatment options.
Scroll Up
Scroll Down
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!