Update on preclinical and clinical efforts on ex-vivo expansion of hematopoietic stem and progenitor cells.

Abstract

Ex-vivo expansion of hematopoietic stem cells (HSCs) is one potential approach to enhance the clinical efficacy of hematopoietic cell transplantation-based therapy for malignant and nonmalignant blood diseases. Here, we discuss the major progress of preclinical and clinical studies on the ex-vivo expansion of human HSCs and progenitor cells (HPCs). Single-cell RNA sequencing identified ADGRG1 as a reliable marker of functional HSCs upon ex-vivo expansion-induced mitochondrial oxidative stress. Both SR1 and UM171 significantly promote ex-vivo expansion of human cord blood HSCs and HPCs, as determined in preclinical animal models. Encouraged by these findings from the bench, multiple phase I/II and phase II clinical trials have been conducted to evaluate the safety, feasibility and efficacy of SR1-expanded and UM171-expanded cord blood units in patients with hematological malignancy. Preliminary data from multiple phase I/II clinical trials regarding transplants of ex-vivo-expanded HSCs and HPCs have demonstrated that ex-vivo expansion may be used to overcome the limitation of the rarity of HSCs without compromising stemness.