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.
Highlights
Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment for high risk hematological and malignant diseases
Possible therapeutic benefit from mesenchymal stromal cells (MSCs) treatment seems to occur in chronic Graft versus host disease (GVHD) patients, the quality of evidence is low as studies had different schemes of infusion (Fisher et al, 2019)
Efficacy of MSC-based treatment is more evident for chronic GVHD patients
Summary
Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment for high risk hematological and malignant diseases. Another study in a mouse model of GVHD reported that the immunosuppression effect of MSCs depends on the recipient’s cytotoxic T cell activity. The authors confirmed that the cytotoxic activity of GVHD patient’s T cells against MSCs was positively correlated with clinical response, which led them to propose the use of an in vitro cytotoxicity test against MSCs to help screening eligible GVHD patients to undergo treatment with MSCs. As many signaling pathways involved in MSCs immunomodulatory effects are mediated by soluble factors, cell-free therapy strategies such as those with MSC-derived exosomes are being considered.
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