Development of Amniotic Epithelial Stem Cells Secretome-Loaded Inverse Electron Demand Diels-Alder-Cross-Linked Hydrogel as a Potential Immunomodulatory Therapeutical Tool.

Amniotic epithelial stem cells (AEC) hold potential for tissue regeneration, especially through their conditioned medium (AEC-CM) due to their immunomodulatory and regenerative effects. Nevertheless, advanced drug delivery systems such as hydrogels are needed to enable clinical applications. Herein, an gellable hyaluronic acid and polyethylene glycol-based iEDDA-cross-linked hydrogel was developed for the encapsulation and controlled release of AEC-CM.

Amphiregulin orchestrates the paracrine immune-suppressive function of amniotic-derived cells through its interplay with COX-2/PGE/EP4 axis.

The paracrine crosstalk between amniotic-derived membranes (AMs)/epithelial cells (AECs) and immune cells is pivotal in tissue healing following inflammation. Despite evidence collected to date, gaps in understanding the underlying molecular mechanisms have hindered clinical applications. The present study represents a significant step forward demonstrating that amphiregulin (AREG) orchestrates the native immunomodulatory functions of amniotic derivatives via the COX-2/PGE/EP4 axis.

Mechanobiological Strategies to Enhance Ovine () Adipose-Derived Stem Cells Tendon Plasticity for Regenerative Medicine and Tissue Engineering Applications.

Adipose-derived stem cells (ADSCs) hold promise for tendon repair, even if their tenogenic plasticity and underlying mechanisms remain only partially understood, particularly in cells derived from the ovine animal model. This study aimed to characterize oADSCs during in vitro expansion to validate their phenotypic properties pre-transplantation. Moreover, their tenogenic potential was assessed using two in vitro-validated approaches: (1) teno-inductive conditioned media (CM) derived from a co-culture between ovine amniotic stem cells and fetal tendon explants, and (2) short- (48 h) and long-term (14 days) seeding on highly aligned PLGA (ha-PLGA) electrospun scaffold.

Stem-Cell-Driven Chondrogenesis: Perspectives on Amnion-Derived Cells.

Regenerative medicine harnesses stem cells' capacity to restore damaged tissues and organs. In vitro methods employing specific bioactive molecules, such as growth factors, bio-inductive scaffolds, 3D cultures, co-cultures, and mechanical stimuli, steer stem cells toward the desired differentiation pathways, mimicking their natural development. Chondrogenesis presents a challenge for regenerative medicine.

Amniotic Membrane and Amniotic Epithelial Cell Culture.

Amniotic membrane (AM) is considered an important medical device for applications in regenerative medicine. The therapeutic properties of AM are due to its resistant extracellular matrix and to the large number of bioactive molecules released by its cells. To this regard, ovine amniotic epithelial cells (AECs) are a subset of placental stem cells with great regenerative and immunomodulatory properties.

Graphene oxide accelerates TGFβ-mediated epithelial-mesenchymal transition and stimulates pro-inflammatory immune response in amniotic epithelial cells.

The application of biomaterials on immune regenerative strategies to deal with unsolved pathologies is getting attention in the field of tissue engineering. In this context, graphene oxide (GO) has been proposed as an immune-mimetic material largely used for developing stem cell-based regenerative therapies, since it has shown to influence stem cell behavior and modulate their immune response. Similarly, amniotic epithelial stem cells (AECs) are getting an increasing clinical interest as source of stem cells due to their great plasticity and immunomodulatory paracrine activities, even though GO bio-mimetic effects still remain unknown.

Mammal comparative tendon biology: advances in regulatory mechanisms through a computational modeling.

There is high clinical demand for the resolution of tendinopathies, which affect mainly adult individuals and animals. Tendon damage resolution during the adult lifetime is not as effective as in earlier stages where complete restoration of tendon structure and property occurs. However, the molecular mechanisms underlying tendon regeneration remain unknown, limiting the development of targeted therapies.

: Insights into hybrid E/M phenotype attitudes.

Epithelial-mesenchymal plasticity (EMP) refers to the ability of cells to dynamically interconvert between epithelial (E) and mesenchymal (M) phenotypes, thus generating an array of hybrid E/M intermediates with mixed E and M features. Recent findings have demonstrated how these hybrid E/M rather than fully M cells play key roles in most of physiological and pathological processes involving EMT. To this regard, the onset of hybrid E/M state coincides with the highest stemness gene expression and is involved in differentiation of either normal and cancer stem cells.

Tendon 3D Scaffolds Establish a Tailored Microenvironment Instructing Paracrine Mediated Regenerative Amniotic Epithelial Stem Cells Potential.

Tendon tissue engineering aims to develop effective implantable scaffolds, with ideally the native tissue's characteristics, able to drive tissue regeneration. This research focused on fabricating tendon-like PLGA 3D biomimetic scaffolds with highly aligned fibers and verifying their influence on the biological potential of amniotic epithelial stem cells (AECs), in terms of tenodifferentiation and immunomodulation, with respect to fleeces. The produced 3D scaffolds better resemble native tendon tissue, both macroscopically, microscopically, and biomechanically.

Tendon Immune Regeneration: Insights on the Synergetic Role of Stem and Immune Cells during Tendon Regeneration.

Tendon disorders represent a very common pathology in today's population, and tendinopathies that account 30% of tendon-related injuries, affect yearly millions of people which in turn cause huge socioeconomic and health repercussions worldwide. Inflammation plays a prominent role in the development of tendon pathologies, and advances in understanding the underlying mechanisms during the inflammatory state have provided additional insights into its potential role in tendon disorders. Different cell compartments, in combination with secreted immune modulators, have shown to control and modulate the inflammatory response during tendinopathies.

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration.

Tendon injuries are at the frontier of innovative approaches to public health concerns and sectoral policy objectives. Indeed, these injuries remain difficult to manage due to tendon's poor healing ability ascribable to a hypo-cellularity and low vascularity, leading to the formation of a fibrotic tissue affecting its functionality. Tissue engineering represents a promising solution for the regeneration of damaged tendons with the aim to stimulate tissue regeneration or to produce functional implantable biomaterials.