Abstract
This study proposes an innovative way to evaluate the homing and tracking of hematopoietic stem cells from young and old mice labeled with SPIONNIRF-Rh conjugated with two types of fluorophores (NIRF and Rhodamine), and their grafting by bioluminescence (BLI) in a bone marrow transplant (BMT) model. In an in vitro study, we isolated bone marrow mononuclear cells (BM-MNC) from young and old mice, and analyzed the physical–chemical characteristics of SPIONNIRF-Rh, their internalization, cell viability, and the iron quantification by NIRF, ICP-MS, and MRI. The in vivo study was performed in a BMT model to evaluate the homing, tracking, and grafting of young and old BM-MNC labeled with SPIONNIRF-Rh by NIRF and BLI, as well as the hematological reconstitution for 120 days. 5FU influenced the number of cells isolated mainly in young cells. SPIONNIRF-Rh had adequate characteristics for efficient internalization into BM-MNC. The iron load quantification by NIRF, ICP-MS, and MRI was in the order of 104 SPIONNIRF-Rh/BM-MNC. In the in vivo study, the acute NIRF evaluation showed higher signal intensity in the spinal cord and abdominal region, and the BLI evaluation allowed follow-up (11–120 days), achieving a peak of intensity at 30 days, which remained stable around 108 photons/s until the end. The hematologic evaluation showed similar behavior until 30 days and the histological results confirm that iron is present in almost all tissue evaluated. Our results on BM-MNC homing and tracking in the BMT model did not show a difference in migration or grafting of cells from young or old mice, with the hemogram analysis trending to differentiation towards the myeloid lineage in mice that received cells from old animals. The cell homing by NIRF and long term cell follow-up by BLI highlighted the relevance of the multimodal nanoparticles and combined techniques for evaluation.
Highlights
This cell migration process to hematopoietic niches localized into bone marrow is known as homing [6]; this active process begins after the hematopoietic stem cell (HSC) administration and does not last more than 48 h [7,8]
This study proposes an innovative way to evaluate the homing and tracking of hematopoietic stem cells from young and old mice labeled with Superparamagnetic Iron
Bone marrow transplantation is a widely used treatment for pathologies of the hemBone marrow is aare widely used treatmentfacing for pathologies of the hematopoiatopoietic system;transplantation there many challenges the improvement of the etic system; there are manyafter challenges facing the improvement of the comprehension comprehension of HSC
Summary
Bone marrow transplantation (BMT) is a therapeutic procedure used as a treatment for a number of hematological diseases, and for some non-hematological diseases [1,2]. It is traditionally performed by the intravenous infusion of hematopoietic stem cell (HSC). Once BMT is performed, the hope is that the cells administered in the circulation will find their way home and repopulate the recipient’s marrow This cell migration process to hematopoietic niches localized into bone marrow is known as homing [6]; this active process begins after the HSC administration and does not last more than 48 h [7,8]. The remainder of the transplanted cells ends up being retained when passing through non-hematopoietic organs, failing to reach the place of interest in BM [9]
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