Treatment of osteonecrosis of the Jaw with mesenchymal stem cells and their secretome
Several exogenous and endogenous insults such as radiation therapy, chemotherapy, trauma, and bone modulating mediations can induce complex changes on bone tissue, and blood vessels, and eventually affect the bone remodelling process, making tissue susceptible to infection and necrosis. Bone necrosis or osteonecrosis (ON) is a health problem that has significant implications for a large number of patients, and there are currently no predictable treatment options. The involvement of ON in the orofacial region, defined as osteonecrosis of the jaw (ONJ), can lead to bone tissue loss, tooth loss, and facial deformity, and these might have consequences of illness, debility, and a deteriorating quality of the patient’s life. Therefore, there is a great demand for a new and highly effective therapeutic approach. Certainly, the secret of the next revolution in the treatment of many diseases lies within each of us. Stem cells are a group of unique cells that can self-regenerate and form cells of different tissues. Since their repopulation after an injury is critical for tissue and organ recovery, the roles of stem cells in treating ONJ or any type of disease cannot be overlooked. However, several studies indicate that the transplanted or injected stem cells do not survive for long, and their therapeutic potential may be due to a wide range of bioactive factors they produce, known as stem cell secretome or conditioned medium (CM). Therefore, in this study, we hypothesize that mesenchymal stem cells (MSC) and/or CM derived from rats with ONJ can reduce inflammation and may have a therapeutic effect on improving bone healing. For this, we will first make ONJ using medication and/or radiation therapy, respectively, followed by extraction of the mandibular left first molar. Then, the therapeutic effect of MSC and/or MSC-CM derived from rats with each ONJ model compared to a healthy MSC and MSC-CM, will be evaluated and compared.
This project will be used as a proof-of-concept model to elucidate the therapeutic effects of MSC, and/or MSC-CM on the treatment of osteonecrotic defects. The results will pave the way for a clinical study using autologous MSC and/or MSC-CM in the treatment of osteonecrosis of the jaws.
We propose to use 211 Lewis rats.
The severity of animal distress should be classified as mild to moderate depending on the model used.
This study will follow the three parts of the legislation and guidelines that regulate ethics when using animals in experiments (3R); Replacement, Reduction, and Refinement, through study design, implementation, reporting, and termination. This will be achieved by following certain measurements such as reducing the number of animals as minimal as possible by using two defects on each animal and observing the animal's status before and after intervention and being in consultation with veterinary medicine in a worse scenario. For more details, various measures are mentioned in the section Alternatives / 3R.
This project will be used as a proof-of-concept model to elucidate the therapeutic effects of MSC, and/or MSC-CM on the treatment of osteonecrotic defects. The results will pave the way for a clinical study using autologous MSC and/or MSC-CM in the treatment of osteonecrosis of the jaws.
We propose to use 211 Lewis rats.
The severity of animal distress should be classified as mild to moderate depending on the model used.
This study will follow the three parts of the legislation and guidelines that regulate ethics when using animals in experiments (3R); Replacement, Reduction, and Refinement, through study design, implementation, reporting, and termination. This will be achieved by following certain measurements such as reducing the number of animals as minimal as possible by using two defects on each animal and observing the animal's status before and after intervention and being in consultation with veterinary medicine in a worse scenario. For more details, various measures are mentioned in the section Alternatives / 3R.