Clinical Translation of Mesenchymal Stromal Cell Therapy for Graft Versus Host Disease

Abstract

Graft versus host disease (GVHD) is a common condition in patients subjected to allogeneic hematopoietic stem cell transplantation (HSCT). The immune cells derived from the grafted stem cells attack recipient’s tissues, including those from the skin, liver, eyes, mouth, lungs, gastrointestinal tract, neuromuscular system, and genitourinary tract, may lead to severe morbidity and mortality. Acute GVHD can occur within few weeks after the allogeneic cells have engrafted in the recipient while chronic GVHD may occur any time after transplant, typically within months. Although treatable by systemic corticosteroid administration, effective responses are not achieved for a significant proportion of patients, a condition associated with poor prognosis. The use of multipotent mesenchymal stromal cells (MSCs) as an alternative to treat steroid-refractory GVHD had improved last decade, but the results are still controversial. Some studies have shown improvement in the life quality of patients after MSCs treatment, while others have found no significant benefits. In addition to variations in trial design, discrepancies in protocols for MSCs isolation, characterization, and ex vivo manipulation, account for inconsistent clinical results. In this review, we discuss the immunomodulatory properties supporting the therapeutic use of MSCs in GVHD and contextualize the main clinical findings of recent trials using these cells. Critical parameters for the clinical translation of MSCs, including consistent production of MSCs according to Good Manufacturing Practices (GMPs) and informative potency assays for product quality control (QC), are addressed.

Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host disease with combination of regulatory T cells

“…However, the mechanism underlying cross talk between MSC and Treg remains unclear [ 46 ]. MSC therapy have also been proposed as a treatment for steroid-refractory GVHD but the results are still controversial [ 47 , 48 ]. Furthermore the origin, delivery route, dose, and timing of infused MSCs influences therapeutic efficacy.…”

Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host diseas with combination of regulatory T cells

“…However, the mechanism underlying cross talk between MSC and Treg remains unclear [46]. MSC therapy have also been proposed as a treatment for steroid-refractory GVHD but the results are still controversial [47,48]. Furthermore the origin, delivery route, dose, and timing of infused MSCs in uences therapeutic e cacy.…”

Oral Mesenchymal Stem/Progenitor Cells: The Immunomodulatory Masters

“…Due to the immunomodulatory function and low immunogenicity of MSCs, autologous/allogenic MSCs obtain good results in the treatment of human autoimmune and inflammatory diseases. Clinical efficacy and safety have been demonstrated for MSCs applied in patients with systematic lupus erythematosus [143][144][145], rheumatic arthritis [146], GVHD [147], and osteoarthritis, [148] via intravenous or local injection, with the results of a decrease in the disease activity score, rebuilding of T cell imbalance, and functional improvement. Nevertheless, despite the inspiring outcomes in clinical trials, it was proposed that MSC transplantation might not be effective in refractory patients in a long-term perspective [149,150].…”