Introduction
toxicity, inflammation, fibrosis, intestinal diseases or skin damage
INFLAMMATION, RECRUITMENT, DISEASES, FIBROSIS
The common thread in a variety of diseases is that injury triggers inflammation, while inflammation intensifies injury and the damaged tissues heal with fibrosis. This is true for liver, kidney, heart, lung, and intestinal diseases or skin damage, such as burn wounds. An ideal therapy for injured organs is not only to regulate (hyper)inflammation, but also to promote tissue repair and regeneration. The bone marrow is a reservoir of stem cells such as hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells, stage-specific embryonic antigen 3 (SSEA3In searching for the mechanisms of liver allograft tolerance, Dr. Sun’s group at the Johns Hopkins University School of Medicine discovered a synergy between AMD3100 (plerixafor) and low-dose FK506 (tacrolimus) (administered at less than one-tenth of the immunosuppressive dose) when injected subcutaneously together. This synergism resulted in healing via the mobilization of bone marrow stem cells and immunoregulatory cells and their recruitment into the sites injured by rejectionBased on these findings, a fixed-dose combination drug containing plerixafor and low-dose tacrolimus, named MRG-001, was developed for subcutaneous (SC) injection by MedRegen, LLC. Preclinical toxicity and pharmacokinetic and pharmacodynamic studies in rats and pigs with more than 6 weeks of treatment every other day demonstrated the drug’s preclinical safety. Here we report the results of the first-in-human trial of MRG-001 in healthy subjects.