Current Stem Cell Research & Therapy - Online First

End-stage liver disease (ESLD) poses a significant threat to human health due to its high mortality rate. Although liver transplantation represents the most effective treatment modality, its application is limited by donor scarcity and prohibitive costs, thereby necessitating the development of innovative and efficacious therapeutic strategies. Within the realm of regenerative medicine, stem cell therapy has emerged as a promising alternative for ESLD treatment, with mesenchymal stem cells (MSCs) being at the forefront due to their exceptional multifunctional differentiation and self-renewal capabilities. Nonetheless, safety concerns, including the potential risk of tumorigenesis associated with MSCs, remain inadequately addressed. Recent evidence indicates that the therapeutic effects of MSCs are primarily mediated through paracrine mechanisms, with MSC-derived exosomes (MSC-Exos) serving as the principal effector mediators. The utilization of exosomes alone for therapeutic purposes not only preserves the beneficial effects of MSCs but also mitigates risks such as tumorigenic potential. Over the past few years, MSC-Exos have demonstrated significant ad-vancements across various medical disciplines, including cardiology, neurology, and gastroenterology. This review outlines the key mechanisms and recent progress in utilizing MSC-Exos in treating end-stage liver disease, seeking to highlight their unique therapeu-tic role.

Cancer is a predominant cause of mortality globally, with both incidence and mortality rates consistently rising. The integrative nature of cancer, characterised by the coexistence of malignant and normal cells, diminishes the efficacy of single-modality therapies for both early-stage and late-stage tumours. Consequently, multimodal interventions, including surgery, radiation, chemotherapy, and immunotherapy, are necessary. Patient heterogeneity and cancer resistance complicate treatment outcomes, requiring personalised therapeutic approaches. Cancer cells operate as astute entities, collaborating with the human body to circumvent treatment, thus necessitating correspondingly intricate therapeutic approaches. Existing medicines are insufficient, rendering cancer a continual struggle for medical professionals and researchers. The progression of nanotechnology has led to the emergence of theranostics, which combines diagnosis and therapy into a unified approach. Nanotheranostic drugs, influenced by external stimuli such as light, magnetic fields, and ultrasound, signify a novel advancement in anti-cancer treatments. Although numerous stimuli-responsive theranostic nanomaterials have demonstrated proof-of-concept, none have progressed to clinical trials. This chapter examines diverse theranostic nanomaterials, emphasising inorganic agents utilised without chemical alterations. It evaluates the efficacy of theranostic agents licensed for preclinical and clinical trials. Chemotheranostics, radiotheranostics, immunotheranostics, and phototheranostics present considerable potential owing to their extensive surface area, customisable attributes, and biocompatibility. Notwithstanding significant progress, difficulties, including particle size, charge, medication stability, and surface changes, remain. Interdisciplinary collaboration among biological, pharmaceutical, materials science, and nanotechnology sectors is crucial for enhancing clinical translation. Tumor-specific theranostic biomaterials offer a targeted methodology, minimising toxicity and improving therapeutic efficacy while accounting for individual patient chracteristics.

Endometriosis is a chronic condition where tissue similar to the endometrium grows outside the uterus, affecting 5-10% of women and causing pelvic pain, painful periods, and infertility. Diseases of the endometrium, the lining of the uterus, can lead to a variety of reproductive health issues, including infertility, irregular bleeding, and endometrial cancer. Researchers have developed advanced in vitro systems using uterine organoids and decellularized tissue scaffolds to understand and model these diseases. The main limitations of traditional 2D monolayer cultures include reduced biological activity, reduced hormone responsiveness, and lack of interaction with ECM. Researchers have investigated 3D culture approaches to address these shortcomings, such as scaffold-free organoids and decellularized tissue scaffolds. Organoid systems can better recapitulate the cellular heterogeneity and physiological functions of the native endometrium. Decellularization protocols have been optimized to generate intact uterine scaffolds that preserve the structural and compositional features of the ECM. Implantation of these bioscaffolds into animal models demonstrated their biocompatibility and regenerative potential. Further refinements of organoid and scaffold technologies, including chemically defined matrices and organ-on-a-chip platforms, will improve our ability to model the uterus. Integration of these advanced in vitro models with patient-derived cells will enable personalized disease modeling and the development of targeted therapies. The combination of organoids, decellularized scaffolds, and microfluidic technologies holds great potential for exploring reproductive biology, drug screening, and developing regenerative therapies for uterine diseases and infertility.