PUBLIC RELEASE DATE:

6-Feb-2014

Contact: Becky Lindeman journal.pediatrics@cchmc.org 513-636-7140 Elsevier Health Sciences

Cincinnati, OH, February 6, 2014 -- Advances in neonatal care for very preterm infants have greatly increased the chances of survival for these fragile infants. However, preterm infants have an increased risk of developing bronchopulmonary dysplasia (BPD), a serious lung disease, which is a major cause of death and lifelong complications. In a new study scheduled for publication in The Journal of Pediatrics, researchers evaluated the safety and feasibility of using stem cell therapies on very preterm infants to prevent or treat BPD.

Won Soon Park, MD, PhD, and colleagues from Samsung Medical Center and Biomedical Research Institute, Seoul, Republic of Korea, conducted a phase I, single-center trial of intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells to nine very preterm infants (24-26 weeks gestational age) who were at high risk of developing BPD.

All patients who received the treatment tolerated the procedure well without any immediate serious adverse effects. Thirty-three percent of treated infants developed moderate BPD and none developed severe BPD, and 72 percent of a matched comparison group developed moderate or severe BPD. Another serious side effect of very preterm birth, retinopathy of prematurity requiring surgery, tended to occur less often in treated infants. Overall, all nine treated infants survived to discharge, and only three developed moderate BPD.

This phase I study suggests that intratracheal administration of mesenchymal stem cells is safe and feasible. According to Dr. Park, "These findings strongly suggest that phase II clinical trials are warranted to test the efficacy of mesencymal stem cell transplantation, which could lead to new therapies to prevent or cure BPD." Dr. Park and colleagues are currently conducting a long-term safety and follow-up study of these nine preterm infants (ClinicalTrials.gov: NCT01632475).

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Stem cells to treat lung disease in preterm infants

A new study, published today in the journal Applied Materials & Interfaces, has found a new method for growing human embryonic stem cells, that doesn't rely on supporting human or animal cells.

Traditionally, these stem cells are cultivated with the help of proteins from animals, which rules out use in the treatment of humans. Growing stem cells on other human cells risks contamination with pathogens that could transmit diseases to patients.

The team of scientists led by the University of Surrey and in collaboration with Professor Peter Donovan at the University of California have developed a scaffold of carbon nanotubes upon which human stem cells can be grown into a variety of tissues. These new building blocks mimic the surface of the body's natural support cells and act as scaffolding for stem cells to grow on. Cells that have previously relied on external living cells can now be grown safely in the laboratory, paving the way for revolutionary steps in replacing tissue after injury or disease.

Dr Alan Dalton, senior lecturer from the Department of Physics at the University of Surrey said: "While carbon nanotubes have been used in the field of biomedicine for some time, their use in human stem cell research has not previously been explored successfully."

"Synthetic stem cell scaffolding has the potential to change the lives of thousands of people, suffering from diseases such as Parkinson's, diabetes and heart disease, as well as vision and hearing loss. It could lead to cheaper transplant treatments and could potentially one day allow us to produce whole human organs without the need for donors."

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The above story is based on materials provided by University of Surrey. Note: Materials may be edited for content and length.

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New stem cell research removes reliance on human and animal cells

49 minutes ago This image shows iPS cells (green) generated using histone variants TH2A and TH2B and two Yamanaka factors (Oct3/4 and Klf4). Credit: RIKEN

One major challenge in stem cell research has been to reprogram differentiated cells to a totipotent state. Researchers from RIKEN in Japan have identified a duo of histone proteins that dramatically enhance the generation of induced pluripotent stem cells (iPS cells) and may be the key to generating induced totipotent stem cells.

Differentiated cells can be coaxed into returning to a stem-like pluripotent state either by artificially inducing the expression of four factors called the Yamanaka factors, or as recently shown by shocking them with sublethal stress, such as low pH or pressure. However, attempts to create totipotent stem cells capable of giving rise to a fully formed organism, from differentiated cells, have failed.

The study, published today in the journal Cell Stem Cell and led by Dr. Shunsuke Ishii from RIKEN, sought to identify the molecule in the mammalian oocyte that induces the complete reprograming of the genome leading to the generation of totipotent embryonic stem cells. This is the mechanism underlying normal fertilization, as well as the cloning technique called Somatic-Cell Nuclear Transfer (SCNT).

SCNT has been used successfully to clone various species of mammals, but the technique has serious limitations and its use on human cells has been controversial for ethical reasons.

Ishii and his team chose to focus on two histone variants named TH2A and TH2B, known to be specific to the testes where they bind tightly to DNA and affect gene expression.

The study demonstrates that, when added to the Yamanaka cocktail to reprogram mouse fibroblasts, the duo TH2A/TH2B increases the efficiency of iPSC cell generation about twentyfold and the speed of the process two- to threefold. And TH2A and TH2B function as substitutes for two of the Yamanaka factors (Sox2 and c-Myc).

By creating knockout mice lacking both proteins, the researchers show that TH2A and TH2B function as a pair, are highly expressed in oocytes and fertilized eggs and are needed for the development of the embryo after fertilization, although their levels decrease as the embryo grows.

In the early embryo, TH2A and TH2B bind to DNA and induce an open chromatin structure in the paternal genome, thereby contributing to its activation after fertilization.

These results indicate that TH2A/TH2B might induce reprogramming by regulating a different set of genes than the Yamanaka factors, and that these genes are involved in the generation of totipotent cells in oocyte-based reprogramming as seen in SCNT.

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Histones may hold the key to the generation of totipotent stem cells