Kick it up a notch Notch could help treat osteoporosis, fractures, arthritis

In addition to Dong, Jesse, and Hilton, the authors include MD / PhD graduate student Anat Kohn and Regis J. Lea Gunnell and teachers O’Keefe, MD, Ph.D., and Michael Zuscik, Ph.D. Tasuko Honjo Kyoto University Graduate School of Medicine have helped.The team has shown that Notch prevents stem cells from maturing. When scientists have activated the Notch pathway, stem cells have not progressed as usual. Instead, they remained indefinitely in an immature state and has no intention to become bone cells, cartilage or connective tissue cells.

Hilton team has shown that in mice a molecule called Notch, which is well known for its influence on blood-forming stem cells and the nervous system, is a key factor in developing mesenchymal stem cells, which constitute a small fraction of cells in bone marrow and other tissues.

Scientists seek new ways to combat diseases, ranging from broken bones to heal, and that has not removed a formidable obstacle, detect and control a key molecular player in order to maintain a kind of prolonged childhood. This step makes the cell treatment in the future more likely for patients.

In a study published online in the journal Development, the team seen as Hilton was able to increase the number and delay the development of stem cells that generate bone, cartilage, muscle and fat. The first authors of the paper are Yufeng Dong, Ph.D., professor and engineer Jesse Alana, who has worked in the laboratory of Hilton Musculoskeletal Research Centre.

The work is part of the ongoing research around the world to exploit the promise of stem cells for human health. Unfortunately, stem cell therapy has been slow to make a real difference in the lives of patients with poor bone and cartilage, Hilton notes, especially since so many questions are currently unanswered.

The laboratory work of Hilton was originally funded by money from the medical center seed. The first results have allowed to draw two scholarships at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institutes of Health and the University filed a patent on the technology of Notch.

“This research helps to lay the groundwork for the testing of new therapies for patients,” he added. “For example, say that the patient is one who simply will not heal. The patient arrives and a bone marrow sample drawn. Their stem cells are isolated from the skeleton and expanded in the laboratory with the activation of Notch-controlled, and then returned to patient to create new bone in large enough to treat the fracture. And ‘hope. ”

The team also set a long-standing issue, the fingering of the molecule-kappa RBPJ the molecule that functions through Notch in the mesenchymal stem cells. This knowledge is essential for scientists trying to understand exactly how Notch function in bone and cartilage. Some years ago, Hilton was part of a team that has shown that Notch is a key regulator of the development of bones and cartilage. The latest study extends these observations by providing important details which suggest that activation and proper management of the road Notch may offer doctors a tool to maintain and expand mesenchymal stem cells for use in the treatment of disease.

“A big problem is that these stem cells to differentiate as quickly – often too fast to make them very useful,” said Matthew J. Hilton, Ph.D., team leader at the University of Rochester Medical Center. ‘It was very difficult to get a good number of stem cells that can still be one of several types of tissues of a patient may need. Having a large population of true stem cells available is a skeleton key to new therapies, and it was a real barrier to date. ”

“To really do the work on stem cell medicine, we need to understand where stem cells come from and how to get to be the cell you want, when and where you want. We are surely in childhood to learn how to manipulate cells stem cells and their use in treatment, “said Hilton, assistant professor of orthopedic surgery and rehabilitation.

Control and delay the development of cells known as mesenchymal (pronounced meh-ZINK-a-mill) stem cells, is a goal long sought by researchers. This is necessary for doctors who want to expand the number of stem cells available for skeletal actual proceedings before the cells start to become specific cell types that may or may not – be required in a patient with, say, the weakness of the bones Osteoporosis, or an old knee injury.