Mechanisms of treatment effects using allogeneic, umbilical cord-derived mesenchymal stromal stem cells (MSCs) in knee osteoarthritis: a pharmacological clinical study protocol.

Background: Knee osteoarthritis (KOA) presents a prevalent orthopedic condition causing substantial impairment in the quality of life and imposing a significant societal and economic burden. Mesenchymal stromal/stem cells (MSCs), known for their regenerative properties and immunomodulatory effects, have emerged as a promising therapeutic avenue in regenerative medicine. Despite MSCs' therapeutic potential, their precise mechanisms of action in KOA remain underexplored.

The issue of heterogeneity of MSC-based advanced therapy medicinal products-a review.

Mesenchymal stromal stem cells (MSCs) possess a remarkable potential for numerous clinical applications due to their unique properties including self-renewal, immunomodulation, paracrine actions and multilineage differentiation. However, the translation of MSC-based Advanced Therapy Medicinal Products (ATMPs) into the clinic has frequently met with inconsistent outcomes. One of the suspected reasons for this issue is the inherent and extensive variability that exists among such ATMPs, which makes the interpretation of their clinical efficacy difficult to assess, as well as to compare the results of various studies.

Factor of time in dendritic cell (DC) maturation: short-term activation of DCs significantly improves type 1 cytokine production and T cell responses.

Dendritic cells (DCs) have been intensively studied in correlation to tumor immunology and for the development DC-based cancer vaccines. Here, we present the significance of the temporal aspect of DC maturation for the most essential subsequent timepoint, namely at interaction with responding T cells or after CD40-Ligand restimulation. Mostly, DC maturation is still being achieved by activation processes which lasts 24 h to 48 h.

Interleukins and interferons in mesenchymal stromal stem cell-based gene therapy of cancer.

The tumor microenvironment is importantly shaped by various cytokines, where interleukins (ILs) and interferons (IFNs) shape the balance of immune activity within tumor niche and associated lymphoid organs. Their importance in activation and tuning of both innate and adaptive immune responses prompted their use in several clinical trials, albeit with limited therapeutic efficacy and risk of toxicity due to systemic administration. Increasing preclinical evidence suggests that local delivery of ILs and IFNs could significantly increase their effectiveness, while simultaneously attenuate the known side effects and issues related to their biological activity.