Multiple sclerosis (MS) is a neuro-inflammatory disorder resulting in neuroaxonal damage in the central nervous system (CNS). Immune-mediated mechanisms triggered during chronic-active demyelination in MS leads to accumulation of myelin debris in the extracellular environment.  It’s well-characterized that Nogo-A, a myelin-associated inhibitory factor, promotes axonal injury by signaling through its receptor Nogo receptor 1 (NgR-1) in MS. Our group utilized the experimental autoimmune encephalomyelitis (EAE) model of MS-like disease, where inflammatory monocytic cells infiltrate CNS lesions. We demonstrate that removing myelin debris using directed delivery of NgR(1-310)ecto-Fc-Myc therapeutic via transplantable hematopoietic stem cells (HSCs) promotes neurorepair. In this study we aimed to specifically define the population of transplanted HSCs that contribute to monocytic cell populations that primarily exert neuro-regenerative effects through their capacity to clear myelin debris. To develop a robust cellular delivery system, we isolated HSCs from wild-type mice and genetically modified them with lentivirus carrying NgR(1-310)ecto-Fc-Myc. We assessed the profile of isolated HSCs and the impact of lentiviral transduction on HSC phenotypic profiles using single-cell RNA sequencing. Transduced HSCs were transplanted into mice, then EAE induced. In the in-vivo phase, we analyzed peripheral blood by flow cytometry and single molecule array to determine immunomodulatory effects of HSC transplantation on recipient mice and to assess levels of axonal degeneration, respectively. Levels of axonal degeneration were coupled with evaluating locomotor performance of mice during the treatment course. Our findings demonstrate that cellular delivery of NgR(310)ecto-Fc-Myc significantly reduced disease severity. This treatment promoted axonal regeneration, remyelination and recovery following clinical decline.