Summary Preclinical studies demonstrate that pharmacological mobilization and recruitment of endogenous bone marrow stem cells and immunoregulatory cells by a fixed-dose drug combination (MRG-001) improves wound healing, promotes tissue regeneration, and prevents allograft rejection. In this phase I, first-in-human study, three cohorts receive subcutaneous MRG-001 or placebo, every other day for 5 days. The primary outcome is safety and tolerability of MRG-001. Fourteen subjects received MRG-001 and seven received a placebo. MRG-001 is safe over the selected dose range. There are no clinically significant laboratory changes. The intermediate dose group demonstrates the most significant white blood cell, stem cell, and immunoregulatory cell mobilization. PBMC RNA sequencing and gene set enrichment analysis reveal 31 down-regulated pathways in the intermediate MRG-001 dose group compared with no changes in the placebo group. MRG-001 is safe across all dose ranges. MRG-001 may be a clinically useful therapy for immunoregulation and tissue regeneration (ClinicalTrials.gov: NCT04646603). Graphical abstract Highlights • MRG-001 exhibits immunoregulatory and regenerative properties in animal models • The phase I trial confirms the favorable safety profile for multiple-dose regimens • Stem cells and immunoregulatory T cells are successfully mobilized by MRG-001 • MRG-001 down-regulates 31 pathways related to inflammation and allograft rejection Ahmadi et al. show that MRG-001, a fixed-dose combination drug, is safe and mobilizes stem and immunoregulatory cells to the circulation, which could act to induce repair and regeneration and modulate inflammation. MRG-001 can potentially be used for treating a variety of human diseases caused by tissue injury and inflammation.
【저자키워드】 stem cells, clinical trial, Safety, Phase I, pharmacokinetics, Pharmacodynamics, tacrolimus, Plerixafor, healthy volunteers, MRG-001,