Therapeutic Potential of Chimeric Antigen Receptor-Expressing Mesenchymal Stem Cells in the Treatment of Inflammatory and Autoimmune Diseases.

Chimeric antigen receptor-engineered mesenchymal stem cells (CAR-MSCs) represent a novel and highly adaptable platform for the targeted treatment of inflammatory and autoimmune diseases. By integrating the inflammation-homing and immunomodulatory properties of mesenchymal stem cells (MSCs) with the antigen-specific recognition and activation potential of chimeric antigen receptors (CARs), CAR-MSCs enable site-specific delivery of therapeutic agents directly to inflamed or diseased tissues. This dual functionality enhances therapeutic precision while minimizing off-target effects and systemic toxicity.

Synchrotron Microbeam Radiotherapy in combination with gold nanoparticles improves control of mouse melanoma.

Introduction: Microbeam Radiation Therapy (MRT) is a preclinical, spatially fractionated radiotherapy technique that delivers ultra-narrow synchrotron x-ray beams at ultra-high dose rates. MRT has demonstrated superior tumor control compared to synchrotron Broad Beam by triggering infiltration of CD8+ T cells and inducing a transient vascular permeability window. This study aimed to investigate the effects of combining MRT with Gold Nanoparticles (AuNPs) on tumor growth, while also assessing whether MRT could enhance intra-tumoral accumulation of AuNPs.

Treatment planning for in vivo multi-fraction, multi-port, multi-modal Synchrotron Radiotherapy.

Background: Treatment planning systems (TPSs) for microbeam radiotherapy (MRT) have seen rapid development over the past few years, however very few TPSs are equipped to handle the growing complexity of in-vivo MRT studies. Current literature lacks sufficient detail for dosimetry, treatment planning, evaluation, and delivery to make meaningful links between dose and treatment outcomes. In a recent study, we investigated treatment outcomes in tumour-bearing mice through modifying temporal placement of MRT fields in a daily-fractionated synchrotron BB schedule.

Effects of Mesenchymal Stem Cells on Functions of Chimeric Antigen Receptor-Expressing T Lymphocytes and Natural Killer Cells.

Chimeric antigen receptor (CAR)-engineered immune cells, particularly CAR T lymphocytes and CAR natural killer (NK) cells, have revolutionized cancer immunotherapy. However, their therapeutic efficacy and safety can be influenced by the tumor microenvironment, particularly the presence of mesenchymal stem cells (MSCs). MSCs are immunomodulatory cells which can alter the function of tumor-infiltrated immune cells in both supportive and suppressive ways.

Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles in the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the gradual loss of dopamine-producing neurons. Oxidative stress, mitochondrial dysfunction, detrimental immune response, and neuroinflammation are mainly responsible for the injury and degeneration of dopaminergic neurons in the brains of patients suffering from PD. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic approach for treating PD due to their ability to suppress the activation of inflammatory immune cells and enhance the viability and function of dopamine-producing neurons.

An Interplay Between Pericytes, Mesenchymal Stem Cells, and Immune Cells in the Process of Tissue Regeneration.

Immediately after injury, damaged cells elicit tissue regeneration, a healing process that enables optimal renewal and regrowth of injured tissues. Results obtained in a large number of experimental studies suggested that the cross talk between pericytes, mesenchymal stem cells (MSC), tissue-resident stem cells, and immune cells has a crucially important role in the regeneration of injured tissues. Pericytes, MSCs, and immune cells secrete bioactive factors that influence each other's behavior and function.

Minibeam Radiation Therapy Valley Dose Determines Tolerance to Acute and Late Effects in the Mouse Oral Cavity.

Purpose: Minibeam radiation therapy (MBRT) is an innovative strategy to improve normal tissue sparing by delivering alternating, submillimeter-wide regions of high "peak" and low "valley" doses. The purpose of this study was to characterize both acute and late MBRT-induced normal tissue toxicities and determine the dosimetric parameters that dictate toxicity.

Methods And Materials: Mice were stratified by weight and randomized to receive a single dose of conventional radiation therapy (uniform open field) or MBRT (0.

Spatially fractionated minibeam radiation delivered at clinically feasible dose rates induces transient vascular permeability.

Microbeam Radiation Therapy is a preclinical form of spatially fractionated radiation therapy that utilizes synchrotron X-rays to deliver highly heterogeneous dose distributions at a micrometric scale. This radiation scheme has been shown to facilitate the induction of controlled and reversible vascular permeability, enhancing treatment efficacy of systemic therapeutic agents. Despite the promising preclinical results, translating microbeam SFRT to the clinic has been hindered by a reliance on synchrotron sources that operate at dose rates orders of magnitude greater than what is possible with clinical machines.

Mesenchymal Stem-Cell-Derived Exosomes as Novel Drug Carriers in Anti-Cancer Treatment: A Myth or Reality?

Although cancer therapy has significantly advanced in recent decades, patients and healthcare professionals are still quite concerned about adverse effects due to the non-targeted nature of currently used chemotherapeutics. Results obtained in a large number of recently published experimental studies indicated that mesenchymal stem-cell-derived exosomes (MSC-Exos), due to their biocompatibility, ability to cross biological barriers, and inherent targeting capabilities, could be used as a promising drug-delivery system for anti-cancer therapies. Their lipid bilayer protects cargo of anti-cancer drugs, making them excellent candidates for the delivery of therapeutic agents.

Mesenchymal Stem Cell-Sourced Exosomes as Potentially Novel Remedies for Severe Dry Eye Disease.

Severe dry eye disease (DED) is an inflammatory condition characterized by a lack of sufficient moisture or lubrication on the surface of the eye, significantly impacting the quality of life and visual function. Since detrimental immune response is crucially responsible for the development and aggravation of DED, therapeutic agents which modulate phenotype and function of eye-infiltrated inflammatory immune cells could be used for the treatment of severe DED. Due to their potent immunomodulatory properties, mesenchymal stem cells (MSCs) represent potentially new remedies for the treatment of inflammatory eye diseases.

Targeted Therapy for Severe Sjogren's Syndrome: A Focus on Mesenchymal Stem Cells.

Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by the infiltration of lymphocytes on salivary and lacrimal glands, resulting in their dysfunction. Patients suffering from severe pSS have an increased risk of developing multi-organ dysfunction syndrome due to the development of systemic inflammatory response, which results in immune cell-driven injury of the lungs, kidneys, liver, and brain. Therapeutic agents that are used for the treatment of severe pSS encounter various limitations and challenges that can impact their effectiveness.

The Impact of Synchrotron Microbeam Radiation Therapy Combined With Broad Beam in a Preclinical Breast Cancer Model.

Purpose: Both local tumor control and distant metastasis are important indicators of the efficacy of radiation therapy treatment. Synchrotron microbeam radiation therapy (MRT), spatially fractionated radiation delivered at ultrahigh dose rates, shows remarkable normal tissue sparing with excellent local control in some models. Some MRT regimens trigger an antitumor immune response that contributes not only to the local but also to systemic treatment efficacy.

Effects of combustible cigarettes and electronic nicotine delivery systems on the regenerative properties of mesenchymal stem cells derived from periodontal ligament (PDL-MSCs).

Introduction: Periodontal ligament-derived mesenchymal stem cells (PDL-MSCs) are promising cells with crucial roles in maintaining and repairing periodontal tissue. However, their regenerative capacity can be influenced by various factors, including cigarette smoke and electronic nicotine delivery system (ENDS) aerosols. Smoking and vaping can impair their regenerative potential, and even though ENDS are perceived as safer tobacco products, there is a lack of evidence to guarantee this assumption.

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Dependent Attenuation of Tear Hyperosmolarity and Immune Cell-Driven Inflammation in the Eyes of Patients with Dry Eye Disease.

Background: Dry eye disease (DED) is a chronic condition characterized by a decrease in tear production or an increase in tear evaporation, leading to inflammation and damage of the ocular surface. Dysfunction of ion channels, tear hyperosmolarity and immune cell-driven inflammation create a vicious circle responsible for the pathological changes in the eyes of DED patients. Mesenchymal stem cells (MSCs) are adult, rapidly proliferating stem cells that produce a large number of immunoregulatory, angiomodulatory, and growth factors that efficiently reduce tear hyperosmolarity-induced pathological changes, inhibit harmful immune response, and provide trophic support to the injured corneal and conjuctival epithelial cells, goblet cells and acinar cells in lacrimal glands of DED patients.

Towards melanoma in situ vaccination with multiple ultra-narrow X-ray beams.

Despite the recent progress, current treatment modalities are not able to eradicate cancer. We show that Microbeam Radiotherapy (MRT), an innovative type of Spatially Fractionated Radiotherapy, can control murine melanoma by activating the host's own immune system. The beneficial effects are very pronounced in comparison to uniform radiotherapy traditionally employed in the clinic.

The Role of MicroRNAs in Mesenchymal Stem Cell-Based Modulation of Pulmonary Fibrosis.

Pulmonary fibrosis is a complex and multifactorial condition that involves a cascade of events, including lung injury, damage of alveolar epithelial cells (AECs), generation of immune cell-driven inflammation, and activation of fibroblasts and their differentiation into myofibroblasts, resulting in the excessive production and deposition of collagen and progressive scarring and fibrosis of the lung tissue. As lung fibrosis advances, the scarring and stiffening of lung tissue can significantly hinder the exchange of oxygen and carbon dioxide, potentially leading to respiratory failure that can be life-threatening. Anti-inflammatory and immunosuppressive drugs are used to slow down the progression of the disease, manage symptoms, and enhance the patient's quality of life.

Effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation: Evidences from diabetic patients and multiple low dose streptozotocin-treated diabetic mice.

Considering detrimental impacts of combustible cigarettes (CCs) on the exacerbation of diabetes mellitus (DM), a significant number of DM patients have substituted CCs with electronic nicotine delivery systems (ENDS). Herewith, we compared CCs and ENDS-dependent modulation of immune cell-driven inflammation in DM patients who used ENDS (DM), CCs (DM) or were non-smokers (DM), paving the way for the better understanding of ENDS-induced biological effects. Multiple low dose streptozotocin (MLD-STZ)-induced mice model of DM was used to support clinical findings.

Thiel cadaver eye as a training model for sub-Tenon's blocks: a feasibility study.

Background: Regional anaesthesia education, especially for ocular procedures, necessitates reliable surgical training models. While cadaveric models offer anatomical fidelity, conventional embalming methods may compromise tissue integrity. We aimed to assess the effectiveness of Thiel cadavers for training in sub-Tenon's blocks by evaluating ocular tissues and measuring insertion forces.

The Effects of Combustible Cigarettes and Electronic Nicotine Delivery Systems on Immune Cell-Driven Inflammation and Mucosal Healing in Ulcerative Colitis.

Introduction: The effects of combustible cigarettes (CCs) and electronic nicotine delivery systems (ENDS) on immune cell-driven colon inflammation and intestinal healing of patients with ulcerative colitis (UC) are still unknown and, therefore, were examined in this study.

Aims And Methods: Intracellular staining and flow cytometry analysis of immune cells isolated from UC patients who used ENDS (UCENDS), CCs (UCCC) and who were nonsmokers (UCAIR) were performed to elucidate cellular mechanisms which were responsible for CCs and ENDS-dependent modulation of immune response during UC progression. Additionally, dextran sulfate sodium (DSS)-colitis was induced in ENDS/CC/air-exposed mice (DSSENDS/ DSSCC/DSSAIR groups) to support clinical findings.

Effects of Combustible Cigarettes and Heated Tobacco Products on Systemic Inflammatory Response in Patients with Chronic Inflammatory Diseases.

Smoke derived from combustible cigarettes (CCs) contains numerous harmful chemicals that can impair the viability, proliferation, and activation of immune cells, affecting the progression of chronic inflammatory diseases. In order to avoid the detrimental effects of cigarette smoking, many CC users have replaced CCs with heated tobacco products (HTPs). Due to different methods of tobacco processing, CC-sourced smoke and HTP-derived aerosols contain different chemical constituents.

Minibeam Radiation Therapy Treatment (MBRT): Commissioning and First Clinical Implementation.

Purpose: Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter-wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT.

Methods And Materials: A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3-, 4-, 5-, 8-, and 10-cm diameter cones.

Effects of combustible cigarettes and heated tobacco products on immune cell-driven inflammation in chronic obstructive respiratory diseases.

Since long-term effects of heated tobacco products (HTP) on the progression of chronic obstructive pulmonary disease (COPD) are unknown, we used COPD mice model to compare immune cell-dependent pathological changes in the lungs of animals which were exposed to HTP or combustible cigarettes (CCs). We also performed intracellular staining and flow cytometry analysis of immune cells which were present in the blood of CCs and HTP users who suffered from immune cell-driven chronic obstructive respiratory diseases. CCs enhanced NLRP3 inflammasome-dependent production of inflammatory cytokines in lung-infiltrated neutrophils and macrophages and increased influx of cytotoxic Th1, Th2, and Th17 lymphocytes in the lungs of COPD mice.

Molecular Mechanisms Responsible for the Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Lung Fibrosis.

Mesenchymal stem cell-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles which contain various MSC-sourced anti-fibrotic, immunoregulatory and angio-modulatory proteins (growth factors, immunoregulatory cytokines, chemokines), lipids, and nucleic acids (messenger RNA and microRNAs). Due to their lipid envelope, MSC-Exos easily by-pass all barriers in the body and deliver their cargo directly in target cells, modulating their viability, proliferation, phenotype and function. The results obtained in recently published experimental studies demonstrated beneficial effects of MSC-Exos in the treatment of lung fibrosis.

Vascular mimicry in zebrafish fin regeneration: how macrophages build new blood vessels.

Vascular mimicry has been thoroughly investigated in tumor angiogenesis. In this study, we demonstrate for the first time that a process closely resembling tumor vascular mimicry is present during physiological blood vessel formation in tissue regeneration using the zebrafish fin regeneration assay. At the fin-regenerating front, vasculature is formed by mosaic blood vessels with endothelial-like cells possessing the morphological phenotype of a macrophage and co-expressing both endothelial and macrophage markers within single cells.