Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
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 3,500+ scientific posters on ePosters
  • More than 5,000+ 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

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
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
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
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
Scientific News
Insight into Eye Diseases
Scientists recreate zebrafish cell regeneration from retinal stem cells in mice.
Analysing 10,000 Cells Simultaneously
New techniquethat traps 10,000 cells on a single chip has potential for cancer screening for individuals.
Studies Explore the Science of Cardiovascular Diseases
Two studies highlight how basic science research insights are key to future treatment breakthroughs.
Stem Cell ‘Heart Patch’ Almost Perfected
Scientists aiming to perfect and test 3D "heart patches" in animal model, last hurdle before human patients.
Using Stem Cells to Grow a 3D Lung-in-a-Dish
Researchers have created 3D lung-like tissue from lung-derived stem cells. The tissue can be used to study lung diseases.
MRI Guidance Aids Stem Cell Delivery
Scientists have delivered stem cells to the brain with unprecedented precision, infusing the cells under real-time MRI guidance.
Mechanisms of Parkinson’s Pathology
Defects that lead to cells’ failure to decommission faulty mitochondria cause nerve cells to die, triggering the symptoms of Parkinson’s disease.
Stem Cell Transplant Without Radiation or Chemotherapy
Researchers have successfully performed stem cell transplants without using radiation or chemotherapy.
Advanced Lymphoma in Remission After T-Cell Therapy
63% of trial participants who recieved two-drug combination chemo plus intermediate dose of engineered T cells went into complete remission.
Inherited Heart Condition Breakthrough
Using stem cells, scientists have created a specific heart condition model, yeilding insights into unexpected disease mechanisms.
Skyscraper Banner

SELECTBIO Market Reports
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!