Genetic effects are influenced by lifestyle

Injured bones reconstructed by gene and stem cell therapies

Date:

May 17, 2017

Source:

Cedars-Sinai

More than 2 million bone grafts, frequently necessitated by severe injuries involving traffic accidents, war or tumor removal, are performed worldwide each year. Such injuries can create gaps between the edges of a fracture that are too large for the bone to bridge on its own. The grafts require implanting pieces from either the patient's or a donor's bone into the gap.

"Unfortunately, bone grafts carry disadvantages," said Gazit, a professor of surgery at Cedars-Sinai. "There are huge unmet needs in skeleton repair."

One problem is that enough healthy bone is not always available for repairs. Surgeries to remove a bone piece, typically from the pelvis, and implant it can lead to prolonged pain and expensive, lengthy hospitalizations. Further, grafts from donors may not integrate or grow properly, causing the repair to fail.

The new technique developed by the Cedars-Sinai-led team could provide a much-needed alternative to bone grafts.

In their experiment, the investigators constructed a matrix of collagen, a protein the body uses to build bones, and implanted it in the gap between the two sides of a fractured leg bone in laboratory animals. This matrix recruited the fractured leg's own stem cells into the gap over a period of two weeks. To initiate the bone repair process, the team delivered a bone-inducing gene directly into the stem cells, using an ultrasound pulse and microbubbles that facilitated the entry of the gene into the cells.

Eight weeks after the surgery, the bone gap was closed and the leg fracture was healed in all the laboratory animals that received the treatment. Tests showed that the bone grown in the gap was as strong as that produced by surgical bone grafts.

"This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal's own stem cells can effectively be used to treat nonhealing bone fractures.

"Our project demonstrates how scientists from diverse disciplines can combine forces to find solutions to today's medical challenges and help develop treatments for the patients of tomorrow," said Bruce Gewertz, MD, surgeon-in-chief and chair of the Department of Surgery at Cedars-Sinai.

Genetic effects are influenced by lifestyle

Date:

September 6, 2017

Source:

Uppsala University

In the current study, researchers have investigated if genetic effects are influenced by different lifestyle factors such as diet, smoking, socio-economic status, alcohol consumption and physical activity. The study builds on genetic and self-reported lifestyle information from 360,000 middle-aged people in the UK.

"The results of our study clearly show that the environment and the lifestyle interact with the genes," says Mathias Rask-Andersen, researcher at the Department of Immunology, Genetics and Pathology, who led the study.

For example, the effect of genetic factors was lower in the most physically active participants. Socio-economic status also influenced the genetic effects. The genetic risk for obesity was more pronounced in participants with lower socio-economic status than in participants with higher socio-economic status. One of the most surprising results of the study was that alcohol consumption also influenced the genetic effects. The researchers could clearly see that the genetic effects were lower among those with more frequent alcohol intake. The genetic effect was nearly half as strong in participants who consume alcohol every day compared with never-drinkers.

The results suggest that we can influence our genetic risk by changing our lifestyle. Someone with a strong predisposition for obesity, for instance a person with many overweight relatives, could reduce the effect of their genes by making lifestyle changes. The hope is that the results of this study will lead to new angles of approach to understanding the mechanisms that regulate body weight and to better methods of treating and preventing obesity and overweight.

"There could be related factors that we do not have information about, which are the real causes of our results. It is therefore important to follow up on our results with more controlled studies to determine cause and effect," says Mathias Rask-Andersen.