Quality Control Analysis of Mesenchymal Stem/Stromal Cells During Investigational New Drug Application for GvHD Administration in China

Abstract

Graft-versus-host disease (GvHD), including the acute and chronic types (aGvHD, cGvHD), arise as the dominating secondary disease in patients with unsatisfying consequences of allogeneic hematopoietic stem cell transplantation (HSCT). Approximately half of GvHD patients were steroid-resistant, with a two-year overall survival rate lower than 20%. Worse still, there are no standardized criteria for an optimal second-line therapy for steroid-resistant aGVHD patients. Notably, pioneering investigators have highlighted the ameliorative or therapeutic effects of human umbilical cord-derived mesenchymal stem/stromal cells (hUC-MSCs) upon GvHD largely attributed to their unique hematopoietic-supporting and immunomodulatory properties. Of note, quality control (QC) is the prerequisite to assure the safety and quality of hUC-MSCs before investigational new drug (IND) applications and large-scale clinical applications. Herein, we summarize the state-of-the-art updates upon IND-associated QC and clinical trials of hUC-MSCs during allogeneic HSCT in China. Meanwhile, the supervisory policy and medical ethics of current licensed MSC products for GvHD administration and the concomitant opportunities and challenges have also been discussed.

Keywords: GvHD; HSCT; QC; UC-MSCs; clinical trials; stem cell transplantation.