Cell-Free Therapies: The Use of Cell Extracts to Mitigate Irradiation-Injured Salivary Glands

SIMPLE SUMMARY: Radiation therapy for cancer treatment can lead to damage to surrounding healthy tissues and organs, like salivary glands. Loss of salivary function leads to a decrease in the quality and quantity of saliva, which increases the chances of oral and systemic infections; causes difficulty in swallowing and loss of taste leading to malnutrition. Current treatment modalities to counter this effect are unable to bring satisfaction to the patients whose quality of life is considerably reduced due to cancer and radiotherapy. Here we provide a comprehensive overview of prospective treatment strategies using stem cell-derived extracts and their comparison with other cell-free- therapies. This work is to serve as a resource for scientists to understand, apply and accelerate this treatment methodology in the clinics where its role will be vital to face this clinical challenge. ABSTRACT: Radiotherapy is a standard treatment for head and neck cancer patients worldwide. However, millions of patients who received radiotherapy consequently suffer from xerostomia because of irreversible damage to salivary glands (SGs) caused by irradiation (IR). Current treatments for IR-induced SG hypofunction only provide temporary symptom alleviation but do not repair the damaged SG, thus resulting in limited treatment efficacy. Therefore, there has recently been a growing interest in regenerative treatments, such as cell-free therapies. This review aims to summarize cell-free therapies for IR-induced SG, with a particular emphasis on utilizing diverse cell extract (CE) administrations. Cell extract is a group of heterogeneous mixtures containing multifunctional inter-cellular molecules. This review discusses the current knowledge of CE’s components and efficacy. We propose optimal approaches to improve cell extract treatment from multiple perspectives (e.g., delivery routes, preparation methods, and other details regarding CE administration). In addition, the advantages and limitations of CE treatment are systematically discussed by comparing it to other cell-free (such as conditioned media and exosomes) and cell-based therapies. Although a comprehensive identification of the bioactive factors within CEs and their mechanisms of action have yet to be fully understood, we propose cell extract therapy as an effective, practical, user-friendly, and safe option to conventional therapies in IR-induced SG.