Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model

Abstract

The hematopoietic stem cell engraftment depends on adequate cell numbers, their homing, and the subsequent short and long-term engraftment of these cells in the niche. We performed a systematic review of the methods employed to track hematopoietic reconstitution using molecular imaging. We searched articles indexed, published prior to January 2020, in PubMed, Cochrane, and Scopus with the following keyword sequences: (Hematopoietic Stem Cell OR Hematopoietic Progenitor Cell) AND (Tracking OR Homing) AND (Transplantation). Of 2191 articles identified, only 21 articles were included in this review, after screening and eligibility assessment. The cell source was in the majority of bone marrow from mice (43%), followed by the umbilical cord from humans (33%). The labeling agent had the follow distribution between the selected studies: 14% nanoparticle, 29% radioisotope, 19% fluorophore, 19% luciferase, and 19% animal transgenic. The type of graft used in the studies was 57% allogeneic, 38% xenogeneic, and 5% autologous, being the HSC receptor: 57% mice, 9% rat, 19% fish, 5% for dog, porcine and salamander. The imaging technique used in the HSC tracking had the following distribution between studies: Positron emission tomography/single-photon emission computed tomography 29%, bioluminescence 33%, fluorescence 19%, magnetic resonance imaging 14%, and near-infrared fluorescence imaging 5%. The efficiency of the graft was evaluated in 61% of the selected studies, and before one month of implantation, the cell renewal was very low (less than 20%), but after three months, the efficiency was more than 50%, mainly in the allogeneic graft. In conclusion, our review showed an increase in using noninvasive imaging techniques in HSC tracking using the bone marrow transplant model. However, successful transplantation depends on the formation of engraftment, and the functionality of cells after the graft, aspects that are poorly explored and that have high relevance for clinical analysis.

Multimodal Tracking of Hematopoietic Stem Cells from Young and Old Mice Labeled with Magnetic–Fluorescent Nanoparticles and Their Grafting by Bioluminescence in a Bone Marrow Transplant Model

“…The quantification of iron load internalized into BM-MNC by NIRF, MRI, and ICP-MS (Table 2) showed signal detection according to the signal detection limitation of each technique as a function of their sensibility, spatial, and temporal resolutions [17,46]. Some studies reported an internalization of 0.69 ± 0.08 [47]; 1.33 ± 0.2 [48]; 2.01 ± 0.10 pg [49] of nanoparticles per HSC.…”

“…Generally, studies about cells homing/tracking after BTM have used ex vivo techniques to quantify HSC in recipient animal; this type of analysis cannot generate data on the migration or grafting dynamic in a single animal longitudinally, since it requires euthanasia at the point of analysis [14][15][16]. However, the cell homing and grafting data can be obtained in a non-invasive way with the use of the molecular image technique [17]. The molecular image comprise a group of image techniques that use the target molecules to track biological processes via in vivo analysis, in a non-invasive way, besides allowing the quantitative analysis [18].…”

“…The molecular image comprise a group of image techniques that use the target molecules to track biological processes via in vivo analysis, in a non-invasive way, besides allowing the quantitative analysis [18]. Bioluminescence Imaging (BLI) is the most commonly used technique for non-invasive HSC tracking in experimental models [17]. We can also highlight techniques such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) and Fluorescence Imaging (FLI), and especially Near-infrared fluorescence (NIRF) that enables the capture of images with greater depth of penetration than fluorescent agents in the visible spectrum, reducing the autofluorescence of tissues [19].…”

“…We can also highlight techniques such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) and Fluorescence Imaging (FLI), and especially Near-infrared fluorescence (NIRF) that enables the capture of images with greater depth of penetration than fluorescent agents in the visible spectrum, reducing the autofluorescence of tissues [19]. Each of these image modalities has advantages and limitations when compared to any other, which is why the development of probes which make it possible to perform a set of images with a single tracking agent has gained a lot of attention due to the multimodal images generated [17,20]. The last systematic review on this topic, Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model, did not show the combined use of the molecular image technique in any of the studies analyzed [17].…”

“…Each of these image modalities has advantages and limitations when compared to any other, which is why the development of probes which make it possible to perform a set of images with a single tracking agent has gained a lot of attention due to the multimodal images generated [17,20]. The last systematic review on this topic, Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model, did not show the combined use of the molecular image technique in any of the studies analyzed [17].…”