Tag: bone marrow

A ‘Fountain of Youth’ for Bone Marrow Stem Cells

Source: National Cancer Institute on Unsplash

Scientists have shown that reduced bone marrow stem cell function with ageing is due to changes in their epigenome, and they were able to reverse these changes in isolated stem cells by adding acetate. This ‘fountain of youth’ for the epigenome could become important for the treatment of diseases such as osteoporosis.

One responsible mechanism for age-related osteoporosis and fracture risk involves the impaired function of the bone-marrow stem cells, which are required for the maintenance of bone integrity. 

For a long time, researchers have looked at epigenetics as a cause of ageing. Epigenetics looks at changes that affect the activity of genes. One of these is changes in proteins called histones, which package and thus control access to DNA. In this study, the researchers investigated the epigenome of mesenchymal stem cells, which are found in bone marrow and can give rise to different types of cells such as cartilage, bone and fat cells.

“We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice,” explained Andromachi Pouikli, first author of the study. “We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected.”

The researchers then sought to find out if it was possible to rejuvenate the epigenome of stem cells. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate. The cell converts the acetate into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. “This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells,” Pouikli said.

To see if this change could also be responsible for increased fracture risk and osteoporosis with age, the researchers studied human mesenchymal stem cells from hip surgery patients. In elderly patients with osteoporosis, the same epigenetic changes seen with mice were also seen in these human cells.

“Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells,” cautioned study leader Peter Tessarz. “However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects.”

The results were published in the journal Nature Aging.

Source: Max Planck Society

Bone Marrow Cell Mutations That Protect Against Cancers

Source: NIH

People with shortened telomeres caused by rare disorders may be more likely to have blood cancers such as leukaemia or myelodyplastic syndrome (MS). Now researchers have discovered several “self-correcting” genetic mutations in bone marrow that may protect such patients from these cancers.

In a study published in the Journal of Clinical Investigation, these mutations can serve as biomarkers to indicate if patients with short telomere syndromes (STS) are likely to develop blood cancers.

“These are the most common cancers we see in patients with short telomere syndromes,” said Mary Armanios, MD, director of the Telomere Center and professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. “We know that at a certain point, the cells of patients with shortened telomeres either become cancerous or stay healthy.”

Dr Armanios and her team suspected that a self-correcting mechanism in areas of the body with high cell turnover, such as bone marrow, was allowing normal cells to turn malignant. Instead, it appears this mechanism protects against cells from becoming cancerous.

As over 300 billion blood cells are produced in the bone marrow daily, the researchers suspected they could find evidence of cellular self-correction in this area of the body, especially amid the spongey interior of bones, where quick adaptation is crucial for high-volume cell production.
The researchers tested the bone marrow and blood cells of 84 study participants divided into three groups: Those with STS and MS or leukaemia; those with short telomere syndromes and no MS or leukemia; and those in the control group without short telomere syndromes or any cancers.

Using ultra-deep genetic sequencing which picks up hard-to-detect mutations, Armanios and her team observed genetic mutations and self-correction in several telomere-associated genes. Nearly a quarter of patients with STS had these mutations, some even showing multiple mutations.

One such mutation in a gene called TERT enables the production of crucial parts of telomerase, which stabilises telomeres. By boosting telomerase production and overwriting faulty copies of the TERT gene, the researchers found that bone marrow cells seemed to self-correct to avoid becoming cancerous.

“Our findings speak to the versatility of the bone marrow and other areas with high cell turnover in the body,” says Armanios. “Such advantageous mutations provide the body with a better chance to protect itself. These findings may be important in the screening process of shortened telomere patients so that we can predict who may be protected from cancer.”

Source: John Hopkins Medicine