Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

T-cells Derived from Human Embryonic Stem Cells May Prevent Graft Rejection

By BiotechDaily International staff writers
Posted on 29 May 2013
Image: Senior author Dr. Matthias Hebrok (Photo courtesy of the University of California, San Francisco).
Image: Senior author Dr. Matthias Hebrok (Photo courtesy of the University of California, San Francisco).
Image: Contributing author Dr. Mark Anderson (Photo courtesy of the University of California, San Francisco).
Image: Contributing author Dr. Mark Anderson (Photo courtesy of the University of California, San Francisco).
A recent paper described the development of a method for using human embryonic stem cells (hESCs) to generate fully functional thymus tissue capable of supporting T-cell development and proliferation.

Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T-cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited.

Investigators at the University of California, San Francisco (USA) developed a new method for directing differentiation of hESCs into thymic epithelial progenitors (TEPs), cells that mature into TECs. The in vitro method was based on the precise chronological regulation of several signaling factors including TGF-beta (transforming growth factor-beta), BMP4 (bone morphogenetic protein 4), Wnt (wingless-type MMTV integration site family), Shh (sonic hedgehog), and FGF (fibroblast growth factor).

Timing the activation of these signaling factors was critical. "If we used one factor for a day longer or shorter it would not work," said senior author Dr. Matthias Hebrok, professor of diabetes research at the University of California, San Francisco. "It would be like driving down the highway and missing your exit."

Results published in the May 16, 2013, online edition of the journal Cell Stem Cell revealed that the hESC-derived TEPs matured into functional TECs that supported T-cell development upon transplantation into thymus-deficient mice. Furthermore, the engrafted TEPs produced T-cells capable of in vitro proliferation as well as in vivo immune responses.

"The thymus is an environment in which T-cells mature, and where they also are instructed on the difference between self and nonself," said contributing author Dr. Mark Anderson, professor of medicine at the University of California, San Francisco. "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."

The protocol described in this study prompted only about 15% of hESCs to differentiate into functional thymus tissue. Even so, Dr. Anderson said, "We now have developed a tool that allows us to modulate the immune system in a manner that we never had before."

Related Links:
University of California, San Francisco



Channels

Drug Discovery

view channel
Image: Wafers like the one shown here are used to create “organ-on-a-chip” devices to model human tissue (Photo courtesy of Dr. Anurag Mathur, University of California, Berkeley).

Human Heart-on-a-Chip Cultures May Replace Animal Models for Drug Development and Safety Screening

Human heart cells growing in an easily monitored silicon chip culture system may one day replace animal-based model systems for drug development and safety screening. Drug discovery and development... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.