Frozen testicular tissue still viable after 20 years

The rate of survival for childhood cancers has increased dramatically in the last several decades, but a serious side effect of treatment is diminished fertility later in life. A potential treatment for boys facing cancer treatment would be to harvest, freeze, and, after the cancer is cured, reimplant their testicular tissue, which contains stem cells that could give rise to sperm.

What happens to that tissue, however, when subjected to the long-term freezing that could be necessary, has remained unclear.

A new study in rats led by University of Pennsylvania School of Veterinary Medicine researchers has shown that male testis tissue that is cryopreserved can be reimplanted after more than 20 years and will go on to make viable sperm. The work, led by senior research investigator Eoin C. Whelan, was published in PLOS Biology.

While the long-frozen testicular tissue could produce sperm, the team found that the long delay did come with a cost in reduced sperm production compared to tissue that is only briefly frozen. The results may have important implications for treatment of prepubertal boys with cancer, for whom chemotherapy may be preceded by harvesting and freezing of testicular tissue for eventual reimplantation.

“The glass-half-empty way of looking at this is that stem cells do seem to be compromised in their ability to regenerate sperm after a long freezing time,” Whelan says. “But the good news is that sperm can be produced, and they seem to be transcriptionally normal when we examined their RNA.”

The study was conducted in the laboratory of Ralph L. Brinster, the Richard King Mellon Professor of Reproductive Physiology at Penn Vet, a renowned scientist of reproductive biology.

Read the full story about this study in Penn Today

Piezo1 Possible Key to Supporting Muscle Regeneration in Duchenne Muscular Dystrophy

One protein, Piezo1, is key to marshalling muscle stem cells’ unique shapes and response to injuries, but it is in low supply in those with Duchenne muscular dystrophy, according to a team at the Perelman School of Medicine at the University of Pennsylvania. However, when they re-activated Piezo1, it allowed muscle stem cells in mice to return to their normal, distinctly-shaped states so that they could repair broken down, dystrophic muscles. These findings, published in Science Advances, open the door to potential molecular-level treatments that may slow or even halt the progression of muscular dystrophy.

“We showed that muscle stem cells have a variety of extensions that are used to sense their environment to respond to injuries, all of which is controlled by the protein Piezo1,” said the study’s lead author, Foteini Mourkioti, PhD, an assistant professor of Orthopaedic Surgery. “This is in contrast to previous belief, which considered muscle stem cells to be simply round and dormant in undamaged muscles.”

Read more about this research in Penn Medicine News.

Penn research shows origin of rare disease FOP rooted in muscle regeneration dysfunction

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by extensive bone growth outside of the normal skeleton that pre-empts the body’s normal responses to even minor injuries. It results in what some term a “second skeleton,” which locks up joint movement and could make it hard to breathe. However, new research in mice by a team at the Perelman School of Medicine at the University of Pennsylvania shows that forming extra-skeletal bone might not be the only driver of the disease. Impaired and inefficient muscle tissue regeneration appears to open the door for unwanted bone to form in areas where new muscle should occur after injuries. This discovery opens up the possibility of pursuing new therapies for FOP and was published today in NPJ Regenerative Medicine.

“While we have made great strides toward better understanding this disease, this work shows how basic biology can provide great insights into appropriate regenerative medicine therapies,” said the study’s lead author, Foteini Mourkioti, PhD, an assistant professor of Orthopaedic Surgery and Cell and Developmental Biology, as well as the co-director of the Penn Institute for Regenerative Medicine, Musculoskeletal Program. “From the lab, we’re now able to show that there is potential for a whole new realm of therapies for patients with this devastating condition.”

Read more about this research in Penn Medicine News.

Changing the identity of cancer cells to eliminate them

In the late 1980s, scientists developed a revolutionary approach to treating acute myeloid leukemia (AML), a type of blood cancer. Called differentiation therapy, it amounted to a bona fide cure for many patients. The treatment works by triggering cells “stuck” with a cancerous identity to keep developing and maturing, giving rise to different, non-disease causing types.

Unfortunately, this treatment only works for a small subset of patients who have a particular subtype of the disease, called promyelocytic AML (APL). “For a long time, it was seen as kind of a one-off,” says M. Andrés Blanco, an assistant professor at the University of Pennsylvania School of Veterinary Medicine.

Now, Blanco and colleagues have identified a new approach to triggering differentiation in AML—one with potential to treat a much wider array of AML patients.

Their study, published in the journal Cancer Discovery, identifies an enzyme that regulates the process by which AML cells differentiate. In both cell lines and an animal model, the researchers found that inhibiting this enzyme, particularly in combination with other anti-cancer therapies, prompted AML cells to lose aspects of their identity associated with aggressive growth. The cells also began to exit the cell cycle, on the path toward maturing into a new cell type.

Read more about Andres’ research in the full post from Penn Today