SHED-derived mesenchymal stromal cell co-infusion is associated with earlier erythroid recovery after autologous hematopoietic cell transplantation: a prospective pilot controlled study

Abstract

Delayed erythroid recovery after autologous hematopoietic stem cell transplantation (AHSCT) contributes to prolonged transfusion requirements and delayed hematopoietic reconstitution. Mesenchymal stromal cells derived from human exfoliated deciduous teeth (SHED-MSCs) exhibit hematopoietic supportive and immunomodulatory properties, but their clinical effects on erythroid recovery after AHSCT remain unknown. We evaluated whether SHED-MSC co-infusion enhances erythroid reconstitution in patients with lymphoma undergoing AHSCT. Fourteen consecutive patients undergoing AHSCT for lymphoma were enrolled in this pilot controlled study, including seven patients receiving SHED-MSC co-infusion and seven controls. Erythroid recovery was assessed longitudinally using absolute reticulocyte count, high-fluorescence reticulocytes (HFR), peak reticulocyte count, and time to predefined reticulocyte recovery. Longitudinal changes were analyzed using linear mixed-effects models adjusted for infused total nucleated cell (TNC) dose. All patients receiving SHED-MSC co-infusion achieved the predefined reticulocyte recovery threshold, whereas only one control patient reached this endpoint ( P = 0.0047). SHED-MSC recipients demonstrated earlier HFR emergence (10.6 ± 0.8 vs. 14.9 ± 5.8 days) and significantly higher peak absolute reticulocyte counts (117.6 ± 29.6 vs. 34.6 ± 22.0 × 10⁹/L; P = 0.0023). Longitudinal mixed-effects analysis demonstrated significantly accelerated erythroid recovery in the SHED-MSC group, and this association remained significant after adjustment for infused TNC dose. SHED-MSC co-infusion was associated with accelerated erythroid reconstitution following AHSCT in patients with lymphoma. These findings provide the first clinical evidence supporting a potential role for SHED-MSCs in enhancing post-transplant erythropoietic recovery and justify validation in larger prospective controlled studies. Iranian Registry of Clinical Trial (IRCT), IRCT20140911019125N10, registered on 29 May 2024.