Cryopreserved apoptotic mesenchymal stromal cells retain functional efficacy in suppressing an allergic inflammation in a murine model.

Mesenchymal stromal cell (MSC) apoptosis is required for in vivo immunosuppression. However, the induction of apoptosis is heavily dependent on the recipient's immune system. In graft-versus-host disease (GvHD), patients who fail to respond to MSCs are in fact those whose immune cells are unable to induce MSC apoptosis ex vivo.

Apoptosis in mesenchymal stromal cells activates an immunosuppressive secretome predicting clinical response in Crohn's disease.

In vivo apoptosis of human mesenchymal stromal cells (MSCs) plays a critical role in delivering immunomodulation. Yet, caspase activity not only mediates the dying process but also death-independent functions that may shape the immunogenicity of apoptotic cells. Therefore, a better characterization of the immunological profile of apoptotic MSCs (ApoMSCs) could shed light on their mechanistic action and therapeutic applications.

The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair.

Mesenchymal stromal cells (MSCs) have been extensively tested for the treatment of numerous clinical conditions and have demonstrated good safety but mixed efficacy. Although this outcome can be attributed in part to the heterogeneity of cell preparations, the lack of mechanistic understanding and tools to establish cell pharmacokinetics and pharmacodynamics, as well as the poorly defined criteria for patient stratification, have hampered the design of informative clinical trials. We and others have demonstrated that MSCs can rapidly undergo apoptosis after their infusion.

Mesenchymal Stromal Cells for Graft Versus Host Disease: Mechanism-Based Biomarkers.

The immunosuppressive activity of mesenchymal stromal cells (MSCs) in graft versus host disease (GvHD) is well-documented, but their therapeutic benefit is rather unpredictable. Prospective randomized clinical trials remain the only means to address MSC clinical efficacy. However, the imperfect understanding of MSC biological mechanisms has undermined patients' stratification and the successful design of clinical studies.

Advances in mesenchymal stromal cell therapy in the management of Crohn's disease.

The aim of therapy in Crohn's disease (CD) is induction and maintenance of remission, promotion of mucosal healing and restoration of quality of life. Even the best treatment regimes, including combinations of biologics and immunomodulators lack durable efficacy and have well documented side effects. Accordingly, there is an unmet need for novel therapies.

Angiopoietin 2 expression in the cornea and its control of corneal neovascularisation.

Purpose: To define proangiogenic angiopoietin 2 (ANG2) expression and role(s) in human and mouse vascularised corneas. Further, to evaluate the effect of ANG2 inhibition on corneal neovascularisation (CNV).

Methods: CNV was induced in FVB mice by means of intrastromal suture placement.

NK1 receptor antagonists as a new treatment for corneal neovascularization.

Purpose: To determine whether the inhibition of Substance P (SP) activity can reduce corneal neovascularization (CNV) by means of local administration of high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonists Lanepitant and Befetupitant.

Methods: We performed a safety and efficacy study by using (1) two different C57BL/6 mouse models of CNV: alkali burn and sutures; (2) different concentrations; and (3) different routes of administration: topical or subconjunctival. Clinical examination endpoints, SP levels, CNV index, and leukocyte infiltration were measured.

Ocular surface injury induces inflammation in the brain: in vivo and ex vivo evidence of a corneal-trigeminal axis.

Purpose: To test whether a corneal injury can stimulate inflammation in the trigeminal ganglion (TG), a structure located in the brain.

Methods: At 4 and 8 days after alkali burn induced in the right eyes of mice, in vivo magnetic resonance imaging (MRI) of the brain was done before and after ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) contrast to track macrophages. Trigeminal ganglia were stained for Prussian Blue and inflammatory cell markers.

Alkali burn versus suture-induced corneal neovascularization in C57BL/6 mice: an overview of two common animal models of corneal neovascularization.

The purpose of the present study was to quantify and compare corneal hem- and lymphangiogenesis between alkali burn and suture-induced corneal neovascularization (CNV) in two commonly used mouse strains. A retrospective analysis was performed on C57BL/6 and FVB neovascularized corneas. CNV was induced by surface caustication with NaOH or intrastromal placement of three 10.

Safety and efficacy of topical infliximab in a mouse model of ocular surface scarring.

Purpose: To evaluate the safety/efficacy of topical infliximab, an anti-TNF-α monoclonal antibody, in a mouse model of ocular surface scarring.

Methods: Twenty alkali burn mice were treated with infliximab (10 mg/mL) topically 6 times a day, while 20 alkali burn mice received saline for 7 days. Corneal opacity, epithelial wound healing, and ocular phimosis were examined at the slit-lamp.