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

Fernando A Oliveira,Fernando Alvieri,Lucas E B Souza,Mariana P Nucci,Igor S Filgueiras,Leopoldo P Nucci,Andrea T Kondo,Nelson Hamerschlak,Lionel F Gamarra,Javier B Mamani,Gabriel N A Rego,João M Ferreira

doi:10.3390/cells9040939

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.

Highlights

Studies from the early 1950s established that total body irradiation in animal models causes death from hemorrhage and infection, indicating that the hematopoietic system is primarily affected [1].Cells 2020, 9, 939; doi:10.3390/cells9040939 www.mdpi.com/journal/cellsit was shown that transplantation of genetically identical bone marrow cells rescues these animals from death induced by irradiation [1].Later on, Edward Donnal Thomas and colleagues pioneered the application of the results from these early animal studies for the treatment of leukemia in humans
Of the 447 articles identified in Pubmed, 114 were excluded after screening (82 reviews, 24 publications before 2000, and 8 publications in other languages) and 325 articles were excluded after assessing eligibility (91 reported no data about hematopoietic stem cell (HSC), 99 reported no data about animal models, and 135 reported no data about noninvasive imaging); only 8 articles were included from this database
Of the 1694 articles identified in Scopus, after screening, 771 articles were excluded (416 reviews, 106 publications before 2000, 50 publications in other languages, and 199 duplicated in Pubmed search), and after assessing eligibility, 910 articles were excluded (287 reported no data about HSC and 623 reported no data about noninvasive imaging); only 13 articles were included from this database

Summary

Introduction

Studies from the early 1950s established that total body irradiation in animal models causes death from hemorrhage and infection, indicating that the hematopoietic system is primarily affected [1].Cells 2020, 9, 939; doi:10.3390/cells9040939 www.mdpi.com/journal/cellsit was shown that transplantation of genetically identical (i.e., syngeneic) bone marrow cells rescues these animals from death induced by irradiation [1].Later on, Edward Donnal Thomas and colleagues pioneered the application of the results from these early animal studies for the treatment of leukemia in humans. Studies from the early 1950s established that total body irradiation in animal models causes death from hemorrhage and infection, indicating that the hematopoietic system is primarily affected [1]. It was shown that transplantation of genetically identical (i.e., syngeneic) bone marrow cells rescues these animals from death induced by irradiation [1]. The approach used here was to kill leukemic cells by high-dose irradiation, followed by restoration of the hematopoietic system with bone marrow transplantation [2]. These early findings provided the rationale for using hematopoietic stem cell transplantation (HSCT) as the first stem cell-based therapy for the treatment of a wide plethora of hematopoietic disorders.

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