ABSTRACT
Therapeutic cells are usually administered as living agents, despite the risks of undesired cell migration and acquisition of unpredictable phenotypes. Additionally, most cell-based therapies rely on the administration of single cells, often associated with rapid in vivo clearance. 3D cellular materials may be useful to prolong the effect of cellular therapies and offer the possibility of creating structural volumetric constructs. Here, the manufacturing of shape-versatile fixed cell-based materials with immunomodulatory properties is reported. Living cell aggregates with different shapes (spheres and centimeter-long fibers) are fixed using a method compatible with maintenance of structural integrity, robustness, and flexibility of 3D constructs. The biological properties of living cells can be modulated before fixation, rendering an in vitro anti-inflammatory effect toward human macrophages, in line with a decreased activation of the nuclear factor kappa B (NF-κB) pathway that preponderantly correlated with the surface area of the materials. These findings are further corroborated in vivo in mouse skin wounds. Contact with fixed materials also reduces the proliferation of activated primary T lymphocytes, while promoting regulatory populations. The fixation of cellular constructs is proposed as a versatile phenotypic stabilization method that can be easily implemented to prepare immunomodulatory materials with therapeutic potential.
ABSTRACT
The study of the interactions of living adherent cells with mechanically stable (visco)elastic materials enables understanding and exploitation of physiological phenomena mediated by cell-extracellular communication. Insights into the interaction of cells and surrounding objects with different stability patterns upon cell contact might unveil biological responses to engineer innovative applications. Here, we hypothesize that the efficiency of cell attachment, spreading, and movement across a free-packed granular bed of microparticles depends on the microparticle diameter, raising the possibility of a necessary minimum traction force for the reinforcement of cell-particle bonds and long-term cell adhesion. The results suggest that microparticles with diameters of 14-20 µm are prone to cell-mediated mobility, holding the potential of inducing early cell detachment, while objects with diameters from 38 to 85 µm enable long-lasting cell adhesion and proliferation. An in silico hybrid particle-based model that addresses the time-dependent biological mechanisms of cell adhesion is proposed, providing inspiration for engineering platforms to address healthcare-related challenges.
Subject(s)
Cell-Derived Microparticles , Cell Adhesion , Computer SimulationABSTRACT
Leishmania is a complex disease caused by the protozoan parasites and transmitted by female phlebotomine sandfly. The disease affects some of the poorest people on earth with an estimated 700,000 to 1 million new cases annually. The current treatment for leishmaniasis is toxic, long, and limited, in view of the high resistance rate presented by the parasite, necessitating new perspectives for treatment. The discovery of new compounds with different targets can be a hope to make the treatment more efficient. Microbial metabolites and their structural analogues with enormous scaffold diversity and structural complexity have historically played a key role in drug discovery. We found thirty-nine research articles published between 1999 and 2021 in the scientific database (PubMed, Science Direct) describing microbes and their metabolites with activity against leishmanial parasites which is the focus of this review. KEY POINTS: ⢠Leishmania affects the poorest regions of the globe ⢠Current treatments for leishmaniasis are toxic and of limited efficacy ⢠Microbial metabolites are potential sources of antileishmania drugs.
