Erythropoietin Gene Expression in the Stromal Cell Increased by Silica to Induce Erythrocyte Differentiation

Silica containing materials are often applied in bone tissue engineering, which may contact with bone marrow cells. However, the biological effects have not always been observed in studies of bone marrow cells exposed to silica. In this experiment, the relevant biological effects were evaluated. Bone marrow cells and stromal cells treated with silica particles (0.5-10 μm) were applied to investigate the possible interaction mechanism. HEL-92 cells were culture with the condition medium of stromal cells treated with or without silica particles. The erythrogenesis of bone marrow cells treated with silica particles was increased significantly. The expression level of glycophorin A the erythroid marker in HEL-92 cells treated by condition medium was higher than control group. The silica particles could also up-regulate the erythropoietin gene expression of stromal cells. The results indicate that bone marrow cells can be stimulated by silica particles to differentiate into erythrocytes. Our results suggest that silica particles can stimulate bone marrow cells to differentiate erythrocytes possibly via enhancing gene expression of erythropoietin.

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Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow

Blood ◽

10.1182/blood.v100.10.3553 ◽

2002 ◽

Vol 100 (10) ◽

pp. 3553-3560 ◽

Cited By ~ 166

Author(s):

Wolf-K. Hofmann ◽

Sven de Vos ◽

Martina Komor ◽

Dieter Hoelzer ◽

William Wachsman ◽

...

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

High Risk ◽

Bone Marrow Cells ◽

Low Risk ◽

Control Group ◽

Expression Data ◽

Hematopoietic Stem ◽

Cd34 Cells ◽

Marrow Cells

Gene patterns of expression in purified CD34+ bone marrow cells from 7 patients with low-risk myelodysplastic syndrome (MDS) and 4 patients with high-risk MDS were compared with expression data from CD34+ bone marrow cells from 4 healthy control subjects. CD34+ cells were isolated by magnetic cell separation, and high-density oligonucleotide microarray analysis was performed. For confirmation, the expression of selected genes was analyzed by real-time polymerase chain reaction. Class membership prediction analysis selected 11 genes. Using the expression profile of these genes, we were able to discriminate patients with low-risk from patients with high-risk MDS and both patient groups from the control group by hierarchical clustering (Spearman confidence). The power of these 11 genes was verified by applying the algorithm to an unknown test set containing expression data from 8 additional patients with MDS (3 at low risk, 5 at high risk). Patients at low risk could be distinguished from those at high risk by clustering analysis. In low-risk MDS, we found that the retinoic-acid–induced gene (RAI3), the radiation-inducible, immediate-early response gene (IEX1), and the stress-induced phosphoprotein 1 (STIP1) were down-regulated. These data suggest that CD34+cells from patients with low-risk MDS lack defensive proteins, resulting in their susceptibility to cell damage. In summary, we propose that gene expression profiling may have clinical relevance for risk evaluation in MDS at the time of initial diagnosis. Furthermore, this study provides evidence that in MDS, hematopoietic stem cells accumulate defects that prevent normal hematopoiesis.

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Evaluation of genotoxicity of pan masala employing chromosomal aberration and micronucleus assay in bone marrow cells of the mice

Toxicology and Industrial Health ◽

10.1177/0748233709345939 ◽

2009 ◽

Vol 25 (7) ◽

pp. 467-471 ◽

Cited By ~ 7

Author(s):

BN Mojidra ◽

K. Archana ◽

AK Gautam ◽

Y. Verma ◽

BC Lakkad ◽

...

Keyword(s):

Bone Marrow ◽

Chromosome Aberration ◽

Chromosomal Aberration ◽

Bone Marrow Cells ◽

Micronucleus Assay ◽

Control Group ◽

Genotoxic Potential ◽

Polychromatic Erythrocytes ◽

Significant Difference ◽

Marrow Cells

Pan masala is commonly consumed in south-east Asian and other oriental countries as an alternate of tobacco chewing and smoking. Genotoxic potential of pan masala (pan masala plain and pan masala with tobacco known as gutkha) was evaluated employing chromosome aberration (CA) and micronucleus (MN) assay in vivo. Animals were exposed to three different doses (0.5%, 1.5% and 3%) of pan masala plain (PMP) and gutkha (PMT) through feed for a period of 6 months and micronucleus and chromosomal aberrations were studied in the bone marrow cells. Induction of mean micronuclei in polychromatic erythrocytes (MNPCE) and normochromatic erythrocyte (MNNCE) was higher in both types of pan masala treated groups with respect to control group. Both pan masala plain and gutkha treatment significantly induced the frequency of MNPCE and MNNCE in the bone marrow cells, indicating the genotoxic potential. Furthermore, slight decline in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was also noticed, suggesting the cytotoxic potential even though the ratio was statistically non significant. A dose-dependent, significant increase in chromosome aberration was observed in both types of pan masala treated mice with respect to control. However, no significant difference in micronucleus and chromosomal aberration induction was noticed between two types of pan masala exposed (PMP and PMT) groups. Results suggest that both types of pan masala, i.e. plain and gutkha, have genotoxic potential.

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Bisecting GlcNAc structure is implicated in suppression of stroma-dependent haemopoiesis in transgenic mice expressing N-acetylglucosaminyltransferase III

Biochemical Journal ◽

10.1042/bj3310733 ◽

1998 ◽

Vol 331 (3) ◽

pp. 733-742 ◽

Cited By ~ 8

Author(s):

Masafumi YOSHIMURA ◽

Yoshito IHARA ◽

Tetsuo NISHIURA ◽

Yu OKAJIMA ◽

Megumu OGAWA ◽

...

Keyword(s):

Bone Marrow ◽

Transgenic Mice ◽

Stromal Cells ◽

Bone Marrow Cells ◽

Adherent Cell ◽

Wild Type ◽

Spleen Cells ◽

Bisecting Glcnac ◽

Marrow Cells

Several sugar structures have been reported to be necessary for haemopoiesis. We analysed the haematological phenotypes of transgenic mice expressing β-1,4 N-acetylglucosaminyltransferase III (GnT-III), which forms bisecting N-acetylglucosamine on asparagine-linked oligosaccharides. In the transgenic mice, the GnT-III activity was elevated in bone marrow, spleen and peripheral blood and in isolated mononuclear cells from these tissues, whereas no activity was found in these tissues of wild-type mice. Stromal cells after long-term cultures of transgenic-derived bone marrow and spleen cells also showed elevated GnT-III activity, compared with an undetectable activity in wild-type stromal cells. As judged by HPLC analysis, lectin blotting and lectin cytotoxicity assay, bisecting GlcNAc residues were increased on both blood cells and stromal cells from bone marrow and spleen in transgenic mice. The transgenic mice displayed spleen atrophy, hypocellular bone marrow and pancytopenia. Bone marrow cells and spleen cells from transgenic mice produced fewer haemopoietic colonies. After lethal irradiation followed by bone marrow transplantation, transgenic recipient mice showed pancytopenia compared with wild-type recipient mice. Bone marrow cells from transgenic donors gave haematological reconstitution at the same level as wild-type donor cells. In addition, non-adherent cell production was decreased in long-term bone marrow cell cultures of transgenic mice. Collectively these results indicate that the stroma-supported haemopoiesis is compromised in transgenic mice expressing GnT-III, providing the first demonstration that the N-glycans have some significant roles in stroma-dependent haemopoiesis.

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Colony formation by primitive haemopoietic progenitors in cocultures of bone marrow cells and stromal cells

British Journal of Haematology ◽

10.1111/j.1365-2141.1985.tb07393.x ◽

1985 ◽

Vol 60 (1) ◽

pp. 129-136 ◽

Cited By ~ 47

Author(s):

M. Y. Gordon ◽

J. A. Hibbin ◽

L. U. Kearney ◽

E. C. Gordon-Smith ◽

J. M. Goldman

Keyword(s):

Bone Marrow ◽

Stromal Cells ◽

Colony Formation ◽

Bone Marrow Cells ◽

Marrow Cells

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Thrombopoietin Is Synthesized by Bone Marrow Stromal Cells

Blood ◽

10.1182/blood.v90.9.3444 ◽

1997 ◽

Vol 90 (9) ◽

pp. 3444-3455 ◽

Cited By ~ 72

Author(s):

Anastasia Guerriero ◽

Lydia Worford ◽

H. Kent Holland ◽

Gui-Rong Guo ◽

Kevin Sheehan ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Progenitor Cells ◽

Stromal Cells ◽

Cell Sorting ◽

Bone Marrow Cells ◽

Adult Bone Marrow ◽

Hla Dr ◽

Adult Bone ◽

Marrow Cells

Abstract We have previously characterized stromal progenitor cells contained in fetal bone marrow by fluorescence-activated cell sorting (FACS) using the differential expression of CD34, CD38, and HLA-DR, and found that a small number were contained within the CD34+ cell fraction. In the present study, the frequency of stromal progenitors in both the CD34+ and CD34− subpopulations from samples of fetal and adult bone marrow was approximately one in 5,000 of the mononuclear cell fraction. Using multiparameter single-cell sorting, one in 20 fetal bone marrow cells with the CD34+, CD38−, HLA-DR−, CDw90+ phenotype were clonogenic stromal progenitors, whereas greater than one in five single cells with the CD34−, CD38−, HLA-DR−, CDw90+ phenotype formed stromal cultures. We found that cultures initiated by hematopoietic and stromal progenitors contained within the CD34+ fraction of bone marrow cells formed mixed hematopoietic/stromal cell cultures that maintained the viability of the hematopoietic progenitor cells for 3 weeks in the absence of added hematopoietic cytokines. We characterized some of the hematopoietic cytokines synthesized by stromal cultures derived from either CD34+ or CD34− bone marrow cells using reverse transcriptase–polymerase chain reaction (RT-PCR) amplification of interleukin-3 (IL-3), stem cell factor (SCF), CD34, Flt3/Flk2 ligand (FL), and thrombopoietin (TPO) mRNA sequences. We found ubiquitous expression of TPO mRNA in greater than 90% of stromal cultures initiated by either CD34+ or CD34− cells, and variable expression of SCF, FL, and CD34 mRNA. In particular, SCF and CD34 mRNA were detected only in stromal cultures initiated by CD34+ bone marrow cells, although the differences between CD34+ and CD34− stromal cells were not statistically significant. IL-3 mRNA was not found in any stromal cultures. An enzyme-linked immunosorbent assay (ELISA) of soluble SCF and TPO present in culture supernatants demonstrated that biologically significant amounts of protein were secreted by some cultured stromal cells: eight of 16 samples of conditioned media from stromal cultures initiated by fetal and adult bone marrow contained more than 32 pg/mL SCF (in the linear range of the ELISA), with a median value of 32 pg/mL (range, 9 to 230), while 13 of 24 samples of conditioned media had more than 16 pg/mL TPO (in the linear range of the ELISA), with a median of 37 pg/mL (range, 16 to 106). Our data indicate that stromal cultures initiated by single bone marrow cells can make FL, SCF, and TPO. Local production of early-acting cytokines and TPO by stromal cells may be relevant to the regulation of hematopoietic stem cell self-renewal and megakaryocytopoiesis in the bone marrow microenvironment.

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Expression of Shelterin ComponentPOT1Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia

Journal of Immunology Research ◽

10.1155/2014/439530 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Ting Wang ◽

Shu-chong Mei ◽

Rong Fu ◽

Hua-quan Wang ◽

Zong-hong Shao

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Telomere Length ◽

Bone Marrow Cells ◽

Culture Media ◽

Telomere Attrition ◽

High Concentrations ◽

Relationship Of ◽

The Relationship ◽

Marrow Cells

Abnormal telomere attrition has been found to be closely related to patients with SAA in recent years. To identify the incidence of telomere attrition in SAA patients and investigate the relationship of telomere length with clinical parameters, SAA patients(n=27)and healthy controls(n=15)were enrolled in this study. Telomere length of PWBCs was significantly shorter in SAA patients than in controls. Analysis of gene expression of Shelterin complex revealed markedly low levels ofPOT1expression in SAA groups relative to controls. No differences in the gene expression of the other Shelterin components—TRF1,TRF2,TIN2,TPP1, andRAP1—were identified. Addition of IFN-γto culture media induced a similar fall in POT1 expression in bone marrow cells to that observed in cells cultured in the presence of SAA serum, suggesting IFN-γis the agent responsible for this effect of SAA serum. Furthermore, ATR, phosphorylated ATR, and phosphorylated ATM/ATR substrate were all found similarly increased in bone marrow cells exposed to SAA serum, TNF-α, or IFN-γ. In summary, SAA patients have short telomeres and decreased POT1 expression. TNF-αand IFN-γare found at high concentrations in SAA patients and may be the effectors that trigger apoptosis through POT1 and ATR.

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Clastogenic Effects of Glyphosate in Bone Marrow Cells of Swiss Albino Mice

Journal of Toxicology ◽

10.1155/2009/308985 ◽

2009 ◽

Vol 2009 ◽

pp. 1-6 ◽

Cited By ~ 33

Author(s):

Sahdeo Prasad ◽

Smita Srivastava ◽

Madhulika Singh ◽

Yogeshwer Shukla

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Positive Control ◽

Vehicle Group ◽

Control Group ◽

Mouse Bone Marrow ◽

Human Beings ◽

Swiss Albino Mice ◽

Albino Mice ◽

Marrow Cells

Glyphosate (N-(phosphonomethyl) glycine,C3H8NO5P), a herbicide, used to control unwanted annual and perennial plants all over the world. Nevertheless, occupational and environmental exposure to pesticides can pose a threat to nontarget species including human beings. Therefore, in the present study, genotoxic effects of the herbicide glyphosate were analyzed by measuring chromosomal aberrations (CAs) and micronuclei (MN) in bone marrow cells of Swiss albino mice. A single dose of glyphosate was given intraperitoneally (i.p) to the animals at a concentration of 25 and 50 mg/kg b.wt. Animals of positive control group were injectedi.p. benzo(a)pyrene (100 mg/kg b.wt., once only), whereas, animals of control (vehicle) group were injectedi.p. dimethyl sulfoxide (0.2mL). Animals from all the groups were sacrificed at sampling times of 24, 48, and 72 hours and their bone marrow was analyzed for cytogenetic and chromosomal damage. Glyphosate treatment significantly increases CAs and MN induction at both treatments and time compared with the vehicle control (P<.05). The cytotoxic effects of glyphosate were also evident, as observed by significant decrease in mitotic index (MI). The present results indicate that glyphosate is clastogenic and cytotoxic to mouse bone marrow.

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Tel-PDGFβR Specifically Induces Interferon-Stimulated Genes.

Blood ◽

10.1182/blood.v106.11.1213.1213 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1213-1213

Author(s):

Hani Kim ◽

Dwayne L. Barber

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Bone Marrow ◽

Fusion Protein ◽

Signaling Pathways ◽

Bone Marrow Cells ◽

Chromosomal Translocations ◽

Time Points ◽

Interferon Stimulated Genes ◽

Marrow Cells

Abstract Chromosomal translocations involving tyrosine kinases play a significant role in human leukemia. Chronic myeloid leukemia (CML) is associated with the recurrent chromosomal translocation, BCR-ABL (t(9;22)(q34;q11)). Chronic myelomonocytic leukemia (CMML) is linked to TEL-PDGF-β Receptor (PDGFβR) (t(5;12)(q33;p13)) fusion. Another TEL fusion, TEL-JAK2 (t(9;12)(p24;p13) has been observed in CMML and Acute Lymphoid Leukemia. All three fusion proteins induce leukemia-like diseases in animal models, and this is attributed to the constitutive tyrosine kinase activity, which leads to dysregulation of their respective downstream signaling pathways. The downstream targets include STAT transcription factors, MAP kinases, and PI3 kinase. On the other hand, little is known about the gene transcription regulated by these fusions. The objective of our study is to determine whether BCR-ABL, TEL-PDGFβR and TEL-JAK2 induce distinct gene expression patterns when expressed in cell lines and retrovirally transduced bone marrow cells. Each fusion was expressed in an IL3-dependent murine myeloid cell line, Ba/F3. The specific inhibitor, Imatinib mesylate, was utilized to control the activation/inhibition of BCR-ABL and TEL-PDGFβR, and an inducible system was utilized for TEL-JAK2. Upon activation of the fusion protein, cells were collected at various time-points for cell cycle and microarray analysis (Affymetrix MOE430A). We utilized 8 hr, 12 hr, 24 hr and 1 wk time points. Our rationale was to monitor gene expression changes through the first cell cycle and then to examine the fingerprint at a steady state point. Analysis of the 1 wk data reveals that a subset of genes are co-regulated (2-fold, p<0.05) by BCR-ABL, TEL-PDGFβR and TEL-JAK2 (Pim1, Id1b, Podxl, Cxcr4, Gp49b and Scin). Interestingly, analysis of the TEL-PDGFβR induced genes (10-fold, p<0.05) revealed a significant overlap with Interferon-Stimulated Gene (ISG) dataset including Cxcl-10, Gbp1, Gbp2, Isg20, Ccl-5, Stat1, Irf7, Serpine-1 and Mx1. Genes identified in this microarray study have been confirmed by Q-PCR in Ba/F3 cells and confirmatory experiments in primary bone marrow cells transduced with each fusion protein are underway. In addition, we will determine whether the transcription of these targets is dependent on STAT1 by utilizing bone marrow cells from STAT1−/− mice. In conclusion, our data reveals that oncogenic chromosomal translocations activate both distinct and co-regulated gene expression and reveal a novel and specific role of Interferon-Stimulated Genes in signaling pathways downstream of TEL-PDGFβR.

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Gene Expression Changes in Bone Marrow Cells from Diamond-Blackfan Anemia Patients.

Blood ◽

10.1182/blood.v104.11.720.720 ◽

2004 ◽

Vol 104 (11) ◽

pp. 720-720 ◽

Cited By ~ 5

Author(s):

Hanna T. Gazda ◽

Despina Sanoudou ◽

Alvin T. Kho ◽

Jan M. Zaucha ◽

Colin A. Sieff ◽

...

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Ribosomal Protein ◽

Cell Population ◽

Bone Marrow Cells ◽

Principal Component ◽

Fold Change ◽

Ribosomal Protein Genes ◽

Diamond Blackfan Anemia ◽

Marrow Cells

Abstract Diamond-Blackfan anemia is usually characterized by anemia, absence or insufficiency of erythroid precursors in bone marrow, growth retardation and diverse congenital anomalies that are present in approximately half of patients, indicating that DBA is a broad disorder of development. Mutations of RPS19 are found in approximately 25% of DBA patients. There is good evidence for a second DBA gene, located on chromosome 8, and further genetic heterogeneity of the disease is likely. The aim of this study is to determine the most disturbed molecular pathways in DBA patients, based on gene expression changes in bone marrow cells. Knowing these pathways will possibly enable us to decipher the pathogenic mechanisms of DBA and find other genes involved in the disease. Bone marrow cells from 6 normal individuals and 3 DBA patients with RPS19 mutations, currently in remission, were FACS separated into 3 populations: primitive (P), erythroid (E) and myeloid (M) containing CD34+CD71-CD45RA-, CD34+CD71hiCD45RA- and CD34+CD71lowCD45RA+ cells, respectively. The purity of each sorted population was >97%. As a control for cell sorting accuracy, methylcellulose assay demonstrated that the P populations were highly enriched in primitive BFU-E and CFU-GEMM colonies, the E populations gave rise to BFU-E and CFU-E colonies in more than 90% of the CFCs, while more than 99% colonies from M populations were CFU-G, CFU-M and CFU-GM. RNA targets from these three FACS sorted cellular subsets was hybridized to Affymetrix HG-U133A chips (>22,000 probe sets). The data from all 27 samples were analyzed by hierarchical clustering and Principal Component Analysis, and each cell population was also studied separately. All pairwise comparisons among 27 datasets showed correlations with r=0.86–0.99. Hierarchical clustering identified three major specimen clusters, perfectly overlapping with the three different cell populations under study. Principal Component 1 and 2 separated the three studied subgroups P, E, and M. In each cell population analysis, 3 patient samples were compared to 6 control samples using 1)Significance Analysis of Microarrays with fold change 2 or greater and false discovery rate 1%, 2)Geometric Fold Change analysis and 3)Filter on Fold Change GeneSpring application (arithmetic analysis). All fold change analyses revealed the most significantly changed transcripts in patients vs. control individuals in E (45 upregulated and 184 downregulated) and P populations. The most changed genes in E subgroup were apoptosis related genes, namely TNFRSF10B and TNFRSF6 (CD95/Fas), upregulated in patients 10 and 3 fold, respectively. Other most changed genes were cancer related and genes involved in developmental processes and nucleic acid binding. Additionally, several ribosomal protein genes, namely RPL10L, RPL28, RPL36, RPL13, RPL27a and RPL37a were significantly underexpressed in P and E populations of DBA patients. All three analyses showed that RPL10L, RPL28 and RPL36 are underexpressed in the M population. This finding indicates that ribosomal protein genes are closely co-regulated and that RPS19 protein abnormalities result in downregulation of the additional ribosomal protein genes in both erythroid and nonerythroid cells in DBA patients.

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Mesenchymal Stromal Cells Enhance G-CSF-Induced Mobilization Of Hematopoietic Stem- and Progenitor Cells

Blood ◽

10.1182/blood.v122.21.2460.2460 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2460-2460

Author(s):

Evert-Jan F. M. de Kruijf ◽

Ingmar van Hengel ◽

Jorge M Perez-Galarza ◽

Willem E. Fibbe ◽

Melissa van Pel

Keyword(s):

Bone Marrow ◽

B Lymphocytes ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Peripheral Blood ◽

Bone Marrow Cells ◽

Calf Serum ◽

Intraperitoneal Administration ◽

Hematopoietic Stem ◽

Marrow Cells

Abstract Hematopoietic stem- and progenitor cell (HSPC) mobilization is a property of most hematopoietic growth factors, such as Granulocyte Colony Stimulating Factor (G-CSF). Not all donors mobilize equally well and therefore the number of HSPC that are obtained following mobilization may be limited. Mesenchymal stromal cells (MSC) have the capacity to differentiate into cells of the mesodermal lineage and have immunomodulatory properties in vivo and in vitro. Here, we have investigated the effect of MSC co-administration on G-CSF-induced HSPC mobilization. MSC were obtained from bone marrow cells (bone marrow-derived) or bone fragments (bone-derived) and were expanded in alpha-MEM containing 10% fetal calf serum until sufficient cell numbers were obtained. Bone marrow or bone-derived MSC were administered intravenously for three days at a dose of 200 x103 cells per day to male C57BL/6 recipients that were simultaneously mobilized with G-CSF (10 μg per day intraperitoneally for 3 days) or PBS as a control. Co-injection of G-CSF and MSC lead to a 2-fold increase in HSPC mobilization compared to G-CSF alone (8,563 ± 3,309 vs. 4,268 ± 1,314 CFU-C per ml peripheral blood respectively; n=13, p<0.01). Administration of MSC alone did not induce HSPC mobilization (273 ± 229 CFU-C/ml blood; n=13). Furthermore, co-injection of splenocytes and G-CSF did not enhance HSPC mobilization, showing that the administration of exogeneous cells as such is not sufficient for enhancement of HSPC mobilization. It has been reported that G-CSF-induced HSPC mobilization is associated with a decrease in the number of osteal macrophages, B lymphocytes and erythroid progenitors. Administration of MSC alone induced a significant decrease in the frequency of osteal macrophages (7.9 ± 1.2 vs 6.2 ± 1.4% bone marrow cells for PBS vs. MSC respectively; n=8, p<0.05), but did not affect osteoblast numbers. Furthermore, the frequency of B lymphocytes was significantly decreased following MSC administration (29.9 ± 4.0 vs. 16.5 ± 4.9% bone marrow cells for PBS vs. MSC respectively; n=13, p<0.0001). No differences were observed in erythroid numbers following MSC administration. To investigate the mechanisms underlying these observations, the migratory capacity of luciferase transduced MSC was studied through bioluminescence imaging. Following intravenous injection, MSC were detected in the lungs, but not in other organs. In addition, no difference in MSC migration was observed between G-CSF and PBS treated mice. Moreover, intraperitoneal administration of G-CSF and MSC resulted in increased HSPC mobilization compared to G-CSF alone (10,178 ±3,039 vs. 5,158 ± 2,436 CFU-C per ml peripheral blood; n=5-12). Together, these data point to an endocrine effect of MSC on G-CSF-induced HSPC mobilization. No differences in IL-6, CXCL-12 or M-CSF levels in bone marrow extracellular fluid were observed. In conclusion, G-CSF-induced HSPC mobilization is enhanced by injection of MSC. We hypothesize that the MSC-induced partial depletion of B lymphocytes and osteal macrophages in the bone marrow are crucial factors involved in the enhancement of G-CSF-induced HSPC mobilization. Disclosures: No relevant conflicts of interest to declare.

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