Journal of bone marrow research最新文献

{"title":"Bone Marrow Stem Cell Contribution to Pulmonary Homeostasis and Disease","authors":"L. McDonald, A. LaRue","doi":"10.4172/2329-8820.1000162","DOIUrl":"https://doi.org/10.4172/2329-8820.1000162","url":null,"abstract":"The understanding of bone marrow stem cell plasticity and contribution of bone marrow stem cells to pathophysiology is evolving with the advent of innovative technologies. Recent data has led to new mechanistic insights in the field of mesenchymal stem cell (MSC) research, and an increased appreciation for the plasticity of the hematopoietic stem cell (HSC). In this review, we discuss current research examining the origin of pulmonary cell types from endogenous lung stem and progenitor cells as well as bone marrow-derived stem cells (MSCs and HSCs) and their contributions to lung homeostasis and pathology. We specifically highlight recent findings from our laboratory that demonstrate an HSC origin for pulmonary fibroblasts based on transplantation of a clonal population of cells derived from a single HSC. These findings demonstrate the importance of developing an understanding of the sources of effector cells in disease state. Finally, a perspective is given on the potential clinical implications of these studies and others addressing stem cell contributions to lung tissue homeostasis and pathology.","PeriodicalId":89965,"journal":{"name":"Journal of bone marrow research","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90439325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of DC-STAMP+ Cells in Human Bone Marrow.","authors":"Yahui Grace Chiu, Christopher T Ritchlin","doi":"10.4172/2329-8820.1000127","DOIUrl":"10.4172/2329-8820.1000127","url":null,"abstract":"<p><p>Osteoclasts (OC), specialized cells derived from monocytes, maintain skeletal homeostasis under normal conditions but degrade bone in patients with rheumatoid (RA) and psoriatic arthritis (PsA). Monocytes initially develop in the bone marrow (BM), circulate in peripheral blood, and differentiate into distinct cell types with diverse functions. Imaging studies in (RA) patients and murine arthritis models demonstrate that bone marrow edema detected on MRI is the result of enhanced myelopoiesis which precedes the development of bone erosions detected on plain radiographs several years later. A major knowledge gap, however, is whether OC develop in the BM and circulate to the joint and if the differentiation to OC takes place in the joint space in response to differentiation signals such as RANKL and TNF. We have previously demonstrated that osteoclast precursors (OCP) are increased in the circulaton of patients with RA and PsA. We showed that DC-STAMP (Dendritic Cell-Specific Transmembrane protein), a 7-pass transmembrane protein expressed on the surface of monocytes, is essential for cell-to-cell fusion during OC differentiation and is a valid biomarker of OCP. Herein, we examined OCP in human bone marrow and identified one novel subset of DC-STAMP+CD45^intermediate monocytes which was absent in the blood. We also found that OCPs reside in human BM with a higher frequency than in the peripheral blood. These findings support the notion that the BM is a major reservoir of circulating OCPs. In addition, we demonstrated that a higher frequency of DC-STAMP+ cells in the BM have detectable intracellular IFN-γ, IL-4 and IL-17A than DC-STAMP+ cells circulating in the peripheral blood. Finally, the frequency of DC-STAMP+ monocytes and T cells is signficantly higher in PsA BM compared to healthy controls, suggesting an enhanced myelopoiesis is a central event in inflammatory arthritis.</p>","PeriodicalId":89965,"journal":{"name":"Journal of bone marrow research","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/ab/nihms-602952.PMC4238037.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32833482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Analysis of Invasive Human Bone Marrow Derived Mesenchymal Stem Cells.","authors":"Lesley A Mathews, Elaine M Hurt, Xiaohu Zhang, William L Farrar","doi":"10.4172/2329-8820.1000122","DOIUrl":"10.4172/2329-8820.1000122","url":null,"abstract":"<p><strong>Background: </strong>Human bone marrow derived mesenchymal stem cells (hMSCs) are capable of differentiation into multiple cell lineages and demonstrate a wide variety of use in various therapeutic applications. Only recently has research begun to understand the gene expression profiles of hMSCs and their differentiated counterparts <i>in vivo</i> and <i>ex vivo</i>.</p><p><strong>Purpose: </strong>The research presented here aimed at gaining a better understanding of gene expression patterns present during hMSC invasion through a basement membrane.</p><p><strong>Methods: </strong>Changes in gene expression were evaluated between invasive and non-invasive cells using Agilent's gene expression arrays and Matrigel invasion chambers. The cells were specifically attracted to a defined stem cell media called SCM.</p><p><strong>Results: </strong>A total 435 genes were up-regulated by 2- fold or more in the invasive population of cells and classified into developmental programs and immunological/inflammatory signaling pathways determined by Ingenuity Pathway Analysis (IPA). This list included a variety of regulators of growth and differentiation including NANOG, STAT3 and STAT5A and members of the polycomb repressive complex-2 (PCRC2) EZH2 and SUZ12. The known regulator of inflammation and hypoxia HIF-1α was also increased suggesting that regulation of the microenvironment is important during this process. Finally, the invasion process could be reversed using the STAT3 inhibitor Static.</p><p><strong>Conclusions: </strong>Overall these data will increase the understanding of the genetic pathways functioning during hMSC invasion and aid in the development of their therapeutic applications.</p>","PeriodicalId":89965,"journal":{"name":"Journal of bone marrow research","volume":"1 ","pages":"122"},"PeriodicalIF":0.0,"publicationDate":"2013-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32296630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The DN2 Myeloid-T (DN2mt) Progenitor is a Target Cell for Leukemic Transformation by the TLX1 Oncogene.","authors":"Lynnsey A Zweier-Renn, Irene Riz, Teresa S Hawley, Robert G Hawley","doi":"10.4172/2329-8820.1000105","DOIUrl":"10.4172/2329-8820.1000105","url":null,"abstract":"<p><strong>Introduction: </strong>Inappropriate activation of the TLX1 (T-cell leukemia homeobox 1) gene by chromosomal translocation is a recurrent event in human T-cell Acute Lymphoblastic Leukemia (T-ALL). Ectopic expression of TLX1 in murine bone marrow progenitor cells using a conventional retroviral vector efficiently yields immortalized cell lines and induces T-ALL-like tumors in mice after long latency.</p><p><strong>Methods: </strong>To eliminate a potential contribution of retroviral insertional mutagenesis to TLX1 immortalizing and transforming function, we incorporated the TLX1 gene into an insulated self-inactivating retroviral vector.</p><p><strong>Results: </strong>Retrovirally transduced TLX1-expressing murine bone marrow progenitor cells had a growth/survival advantage and readily gave rise to immortalized cell lines. Extensive characterization of 15 newly established cell lines failed to reveal a common retroviral integration site. This comprehensive analysis greatly extends our previous study involving a limited number of cell lines, providing additional support for the view that constitutive TLX1 expression is sufficient to initiate the series of events culminating in hematopoietic progenitor cell immortalization. When TLX1-immortalized cells were co-cultured on OP9-DL1 monolayers under conditions permissive for T-cell differentiation, a latent T-lineage potential was revealed. However, the cells were unable to transit the DN2 myeloid-T (DN2mt)-DN2 T-lineage determined (DN2t) commitment step. The differentiation block coincided with failure to upregulate the zinc finger transcription factor gene Bcl11b, the human ortholog of which was shown to be a direct transcriptional target of TLX1 downregulated in the TLX1⁺ T-ALL cell line ALL-SIL. Other studies have described the ability of TLX1 to promote bypass of mitotic checkpoint arrest, leading to aneuploidy. We likewise found that diploid TLX1-expressing DN2mt cells treated with the mitotic inhibitor paclitaxel bypassed the mitotic checkpoint and displayed chromosomal instability. This was associated with elevated expression of TLX1 transcriptional targets involved in DNA replication and mitosis, including Ccna2 (cyclin A2), Ccnb1 (cyclin B1), Ccnb2 (cyclin B2) and Top2a (topoisomerase IIα). Notably, enforced expression of BCL11B in ALL-SIL T-ALL cells conferred resistance to the topoisomerase IIα poison etoposide.</p><p><strong>Conclusion: </strong>Taken together with previous findings, the data reinforce a mechanism of TLX1 oncogenic activity linked to chromosomal instability resulting from dysregulated expression of target genes involved in mitotic processes. We speculate that repression of BCL11B expression may provide part of the explanation for the observation that aneuploid DNA content in TLX1⁺ leukemic T cells does not necessarily portend an unfavorable prognosis. This TLX1 hematopoietic progenitor cell immortalization/T-cell differentiation assay sho","PeriodicalId":89965,"journal":{"name":"Journal of bone marrow research","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191823/pdf/nihms-470705.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32742880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow Failure Syndromes: The Ribosomopathies.","authors":"A. Khanna-Gupta","doi":"10.4172/2329-8820.1000106","DOIUrl":"https://doi.org/10.4172/2329-8820.1000106","url":null,"abstract":"In recent years a number of human diseases associated with dysregulated ribosome biogenesis have been identified and categorized as “ribosomopathies” [1]. Acquired or congenital genetic lesions leading to impaired ribosome biogenesis and function appear to be germane to this class of disorders that include Diamond-Blackfan anemia (DBA), a disorder characterized by pure red cell aplasia, Shwachman-Diamond syndrome (SDS), dyskeratosis congenita (DC), cartilage hair hypoplasia (CHH), Treacher Collins syndrome (TCS), and del (5q), a type of myelodysplastic syndrome (MDS). While each of these disorders is associated with distinct mutations in the ribosome biogenesis pathway (Figure 1), bone marrow failure appears to be a uniformly observed clinical symptom. However, the affected lineages appear to be uniquely syndrome-specific. For example, the erythroid and megakaryocytic lineages are affected in DBA and del (5q) MDS, while neutropenia predominates in SDS.","PeriodicalId":89965,"journal":{"name":"Journal of bone marrow research","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73150753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow Failure Syndromes: The Ribosomopathies.","authors":"Arati Khanna-Gupta","doi":"10.4172/jbmr.1000106","DOIUrl":"https://doi.org/10.4172/jbmr.1000106","url":null,"abstract":"","PeriodicalId":89965,"journal":{"name":"Journal of bone marrow research","volume":"1 106","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757936/pdf/nihms470695.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31702187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta Blockade Protection of Bone Marrow Following Injury: A Critical Link between Heart Rate and Immunomodulation.","authors":"Gregg M Baranski,&nbsp;Latha V Pasupuleti,&nbsp;Ziad C Sifri,&nbsp;Kristin M Cook,&nbsp;Walter D Alzate,&nbsp;Pranela Rameshwar,&nbsp;David H Livingston,&nbsp;Alicia M Mohr","doi":"10.4172/2329-8820.1000124","DOIUrl":"https://doi.org/10.4172/2329-8820.1000124","url":null,"abstract":"<p><strong>Introduction: </strong>Severe trauma induces a profound elevation of catecholamines that is associated with bone marrow (BM) hematopoietic progenitor cell (HPC) colony growth suppression, excessive BM HPC mobilization, and a persistent anemia. Previously, propranolol (BB) use after injury and shock has been shown to prevent this BM dysfunction and improve hemoglobin levels. This study seeks to further investigate the optimal therapeutic dose and timing of BB administration following injury and shock.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were subjected to a combined lung contusion (LC), hemorrhagic shock (HS) model ± BB. In our dose response experiments, animals received BB at 1, 2.5, 5, or 10 mg/kg immediately following resuscitation. In our therapeutic window experiments, following LCHS rats were given BB immediately, 1 hour, or 3 hours following resuscitation. BM and peripheral blood (PB) were collected in all animals to measure cellularity, BM HPC growth, circulating HPCs, and plasma G-CSF levels.</p><p><strong>Results: </strong>Propranolol at 5 and 10 mg/kg significantly reduced HPC mobilization, restored BM cellularity and BM HPC growth, and decreased plasma G-CSF levels. Propranolol at 5 and 10 mg/kg also significantly decreased heart rate. When BB was administered beyond 1 hour after LCHS, its protective effects on cellularity, BM HPC growth, HPC mobilization, and plasma G-CSF levels were greatly diminished.</p><p><strong>Conclusion: </strong>Early Buse following injury and shock at a dose of at least 5mg/kg is required to maintain BM cellularity and HPC growth, prevent HPC mobilization, and reduce plasma G-CSF levels. This suggests that propranolol exerts its BM protective effect in a dose and time dependent fashion in a rodent model. Finally, heart rate may be a valuable clinical marker to assess effective dosing of propranolol.</p>","PeriodicalId":89965,"journal":{"name":"Journal of bone marrow research","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2329-8820.1000124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33003112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Bone Marrow in Pathogenesis of Viral Infections.","authors":"Guey Chuen Perng","doi":"10.4172/2329-8820.1000104","DOIUrl":"https://doi.org/10.4172/2329-8820.1000104","url":null,"abstract":"Bone marrow suppression is a well-recognized clinical observation documented in virus-induced human diseases [1,2]. Despite the exquisite details that have been uncovered about viruses and illness, it is unknown how the bone marrow becomes engaged and contributes to pathogenesis. It is pertinent that we understand the role of this compartment during infection because it is the root of all hematopoietic cells circulating in the peripheral blood [3]. Historically, the importance of the bone marrow in orchestrating immune cell production has been well-documented and fully-established [4]. But due to its difficulty to access, isolate and culture, peripheral blood components have overtaken the stage of investigations on the causative development of diseases. Even though peripheral hematopoietic cells and their activities are resultant of the compartment from which they derive, investigating these cells cannot tell us what is happening in the bone marrow. The interaction between the pathogen and the bone marrow compartment and how this contributes to patient symptoms is still an enigma. In the advent of escalating success in treating conditions, such as sickle cell anemia, with cells originating from the bone marrow [5], we should feel prompted to pay extra attention to the physiology of the bone marrow cells. Questions, such as, does bone marrow play a role in the pathogenic causes of viral disease? If yes, to what extent? Furthermore, how is it involved in the process? Investigating these topics will allow us to begin to dissect the role of the bone marrow in the physiological maintenance during infection and the manifestation of disease.","PeriodicalId":89965,"journal":{"name":"Journal of bone marrow research","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2329-8820.1000104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32722319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}