Optimized GMP-grade Wharton’s jelly’s mesenchymal stromal cells manufacturing and administration protocol for Graft versus Host disease prevention

Abstract

Background

Wharton's jelly mesenchymal stromal cells (WJ-MSCs) are multipotent cells derived from the umbilical cord with immunomodulatory properties, making them a promising candidate for cell-based therapies targeting immune-related diseases. Herein, we aim to optimize the conditions of use of clinical-grade WJ-MSCs manufactured according to Good Manufacturing Practice (GMP) for the prevention of graft versus host disease (GVHD) in a preclinical xenogeneic GVHD mouse model.

Methods

GMP-compliant WJ-MSCs were primed with IFN-γ and assessed in vitro for their immunosuppressive capacity using coculture assays with activated human T cells. To evaluate in vivo efficacy, NSG mice were sub-lethally irradiated (2 Gy) and transplanted with human peripheral mononuclear cells, then treated with one or more injections of IFN-γ-primed or unprimed WJ-MSCs, to assess xeno- GVHD and its severity.

Results

GMP-produced WJ-MSCs suppressed T-cell proliferation in vitro and IFN-γ priming enhanced this effect, largely through Indoleamine 2,3-dioxygenase (IDO) activity. In vivo, three weekly injections of IFN-γ-primed WJ-MSCs significantly improved survival and reduced histological GVHD scores in the liver and skin of recipient mice.

Conclusion

These findings demonstrate that IFN-γ-primed GMP-grade WJ-MSCs effectively prevent GVHD in preclinical models, and support their use in optimized dosing regimens for future clinical testing. Given their enhanced immunosuppressive efficacy, they also hold promise as a therapeutic option for established and treatment-refractory forms of GVHD.