The bone marrow (BM) plays a pivotal role in homeostasis by supporting hematopoiesis and immune cells' activation, maturation, interaction, and deployment. "BMSC-derived secretome" refers to the complete repertoire of secreted molecules, including nucleic acids, chemokines, growth factors, cytokines, and lipids from BM-derived mesenchymal stem cells (BMSCs). BMSC-derived secretomes are the current molecular platform for acellular therapy. Secretomes are highly manipulable and can be synthesised in vast quantities using commercially accessible cell lines in the laboratory. Secretomes are less likely to elicit an immunological response because they contain fewer surface proteins. Moreover, the delivery of BMSC-derived secretomes has been shown in numerous studies to be an effective, cell-free therapy method for alleviating the symptoms of inflammatory and degenerative diseases. As a result, secretome delivery from BMSCs has the same therapeutic effects as BMSCs transplantation but may have fewer adverse effects. Additionally, BMSCs' secretome has therapeutic promise for organoids and parabiosis studies. This review focuses on recent advances in secretome-based cell-free therapy, including its manipulation, isolation, characterisation, and delivery systems. The diverse bioactive molecules of secretomes that successfully treat inflammatory and degenerative diseases of the musculoskeletal, cardiovascular, nervous, respiratory, reproductive, gastrointestinal, and anti-ageing systems were also examined in this review. However, secretome-based therapy has some unfavourable side effects that may restrict its uses. Some of the adverse effects of this modal therapy were briefly mentioned in this review.
Background: Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females, especially those of European descent. The interplay between environmental factors and genetic predisposition plays a crucial role in MS etiopathogenesis. Methods: We searched recent relevant literature on reputable databases, which include, PubMed, Embase, Web of Science, Scopus, and ScienceDirect using the following keywords: multiple sclerosis, pathogenesis, autoimmunity, demyelination, therapy, and immunotherapy. Results: Various animal models have been employed to investigate the MS etiopathogenesis and therapeutics. Autoreactive T cells within the CNS recruit myeloid cells through chemokine expression, leading to the secretion of inflammatory cytokines driving the MS pathogenesis, resulting in demyelination, gliosis, and axonal loss. Key players include T cell lymphocytes (CD4+ and CD8+), B cells, and neutrophils. Signaling dysregulation in inflammatory pathways and the immunogenetic basis of MS are essential considerations for any successful therapy to MS. Data indicates that B cells and neutrophils also have significant roles in MS, despite the common belief that T cells are essential. High neutrophil-to-lymphocyte ratios correlate with MS severity, indicating their contribution to disease progression. Dysregulated signaling pathways further exacerbate MS progression. Conclusion: MS remains incurable, but disease-modifying therapies, monoclonal antibodies, and immunomodulatory drugs offer hope for patients. Research on the immunogenetics and immunoregulatory functions of gut microbiota is continuing to provide light on possible treatment avenues. Understanding the complex interplay between genetic predisposition, environmental factors, and immune dysregulation is critical for developing effective treatments for MS.