To treat a complicated, non-healing bone defect, surgeons often use an implant with living cells to promote bone repair, but the implanted cells have a small chance of surviving because they are not prepared for a lack of oxygen and nutrients at the fracture site. Scientists from KU Leuven have now improved survival of these bone cells by preconditioning them to withstand the harmful environment before implantation. Their findings were published in Cell Metabolism.
When breaking an arm or leg, your body can repair the fracture itself in most cases. However, the body’s repair capacity is not sufficient in large bone fractures or defects, which often fail to heal without help. To support bone generation, researchers worldwide are now developing living implants, consisting of cells seeded on supporting structures made of biological material.
Unfortunately, many obstacles still need to be tackled before we have a functional living implant, explains Professor Geert Carmeliet of the Clinical and Experimental Endocrinology Unit. “Often, only 30% of the implanted bone cells will survive the first days. A major reason is that the blood vessels around the fracture, which deliver oxygen and nutrients to the cells, are also damaged. The ingrowth of new blood vessels into the implant takes time and until then, the cells are out of fuel since oxygen and nutrient supply is insufficient. At the same time, the starved bone cells produce harmful oxygen radicals and thereby disturb the natural balance between antioxidants and oxygen radicals. An excess of these oxygen radicals causes irreversible cell damage.”
Doctoral student Steve Stegen tested in mice how he could better equip the bone cells for that crucial stage between implantation and ingrowth of the blood vessels. He managed to switch on a survival mode in bone cells by inactivating the oxygen sensor PHD2 before implantation. “As a result, bone cells activate a dual defence mechanism. First, bone cells increase storage of an emergency fuel in the form of glycogen, which is in fact a sugar reservoir. In addition, bone cells start using glutamine — an amino acid — to produce more antioxidants to neutralise the increased production of harmful oxygen radicals. These two adjustments allow bone cells to be self-supporting in terms of energy generation and to protect themselves against an increased level of oxygen radicals.”
The oxygen sensor PHD2 can be inactivated via genetic engineering, but, more interestingly for use in the clinical setting, also by administering therapeutic molecules, explains Professor Carmeliet. “Reprogramming bone cells obtained from patients might increase their survival rate from 30% to 60%, which will ultimately lead to better bone regeneration. In future research, we will examine whether this technique also works in even larger bone defects and by using human cells.”
The Latest on: Reprogramming bone cells
via Google News
The Latest on: Reprogramming bone cells
- TAU Researchers’ Discovery of Immune System’s ‘Double Agents’ May Help Win War on Canceron October 4, 2021 at 6:54 am
The study was published in the prestigious journal Cell Reports (Exploring the longitudinal glioma microenvironment landscape uncovers reprogrammed pro-tumorigenic neutrophils in the bone marrow).
- Therapeutic Vaccination and Novel Strategies to Treat Chronic HBV Infectionon September 30, 2021 at 5:01 pm
Adoptive transfer of bone marrow in HBV chronic patients ... New strategies to reprogram HBV-specific T-cell functionality (PD-1/apoptosis blockade) or to engineer HBV-specific T cells (genetic ...
- Celebrating the 50th: UTSA professor Amina Qutub explores brain health in March 26 lectureon September 28, 2021 at 5:00 pm
Her research team is developing tightly coupled experimental-computational methods to identify fundamental mechanisms of cell communication in the bone marrow and brain ... we model how stem cells ...
- Towards Personalized Cell-Replacement Therapies for Brain Repairon September 28, 2021 at 5:00 pm
Umbilical cord stem cells and bone marrow stem cells have also raised ... Derivation of autologous pluripotent stem cells by nuclear reprogramming is considered the basis for any potential use ...
- A sound of hope for tinnitus victimson September 26, 2021 at 5:00 pm
The sonic brain reprogramming treatment ... which are sent through the skin and into the bone of the skull. The vibrations stimulate the nerve cells, which respond as if they were hearing high ...
- UAE to test effectiveness of CAR T-cell therapy for treating blood cancerson September 23, 2021 at 9:48 am
These reprogrammed cells become a living drug that mobilises ... director of the Abu Dhabi Bone Marrow Transplant Programme (AD-BMT) and co-principal investigator of the CAR T-cell clinical ...
- UAE to test effectiveness of CAR T-cell therapy for treating blood cancerson September 22, 2021 at 5:00 pm
These reprogrammed cells become a living drug that mobilises through the body, continually tapping the immune system to attack disease. Explaining the significance of the clinical trial, Dr Fatema Al ...
- News tagged with cancer cellson September 21, 2021 at 5:00 pm
New research from Washington University School of Medicine in St. Louis suggests that radiation therapy can reprogram heart muscle cells to what ... for that brittle-bone disease and for bone ...
via Bing News