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

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          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.

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          Most cited references66

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          Graft-versus-host disease.

          Haemopoietic-cell transplantation (HCT) is an intensive therapy used to treat high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. The main complication of HCT is graft-versus-host disease (GVHD), an immunological disorder that affects many organ systems, including the gastrointestinal tract, liver, skin, and lungs. The number of patients with this complication continues to grow, and many return home from transplant centres after HCT requiring continued treatment with immunosuppressive drugs that increases their risks for serious infections and other complications. In this Seminar, we review our understanding of the risk factors and causes of GHVD, the cellular and cytokine networks implicated in its pathophysiology, and current strategies to prevent and treat the disease. We also summarise supportive-care measures that are essential for management of this medically fragile population.
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            A molecular imaging primer: modalities, imaging agents, and applications.

            Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine.
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              One million haemopoietic stem-cell transplants: a retrospective observational study.

              The transplantation of cells, tissues, and organs has been recognised by WHO as an important medical task for its member states; however, information about how to best organise transplantation is scarce. We aimed to document the activity worldwide from the beginning of transplantation and search for region adapted indications and associations between transplant rates and macroeconomics.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                10 April 2020
                April 2020
                : 9
                : 4
                : 939
                Affiliations
                [1 ]Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; fernando.anselmo@ 123456einstein.br (F.A.O.); igor.filgueiras@ 123456usp.br (I.S.F.); joaomatiasferreirav@ 123456gmail.com (J.M.F.); javierbm@ 123456einstein.br (J.B.M.); fernando.alvieri@ 123456einstein.br (F.A.); gabriel.nery@ 123456einstein.br (G.N.A.R.); andrea.kondo@ 123456einstein.br (A.T.K.); hamer@ 123456einstein.br (N.H.)
                [2 ]LIM44—Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-903, Brazil; mariana.nucci@ 123456hc.fm.usp.br
                [3 ]Centro Universitário do Planalto Central, Brasília DF 72445-020, Brazil; leopoldo.nucci@ 123456gmail.com
                [4 ]Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto SP 14049-900, Brazil; lucasebsouza@ 123456usp.br
                Author notes
                [* ]Correspondence: lionelgamarra7@ 123456gmail.com ; Tel.: +55-11-2151-0243
                Author information
                https://orcid.org/0000-0002-7226-1694
                https://orcid.org/0000-0002-1502-9215
                https://orcid.org/0000-0002-3910-0047
                Article
                cells-09-00939
                10.3390/cells9040939
                7226958
                32290257
                463cb2e6-3f15-4a8d-b4e6-93c309cab158
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 February 2020
                : 03 April 2020
                Categories
                Review

                hematopoietic stem cell,nanoparticle,homing,tracking,near-infrared fluorescence image,magnetic resonance image,bioluminescence,molecular imaging,noninvasive imaging

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