scholarly journals Serotonin Targeting Using Common Antidepressants Induces Rapid Recovery of Cytopenia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3715-3715
Author(s):  
Tereza Coman ◽  
Guillemette Fouquet ◽  
Julien Rossignol ◽  
Jean-Henri Bourhis ◽  
Olivier Hermine ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Steady State ◽  
Research Funding ◽  
Control Group ◽  
Hematopoietic Growth Factors ◽  
Hematopoietic Stem ◽  
Post Irradiation ◽  
Hematopoietic Recovery ◽  
Lethal Irradiation

Background. Hematopoiesis is a highly regulated system where multiple, yet undiscovered, factors orchestrate the self-renewal of bone marrow stem cells and their differentiation into blood cells. Following acute stresses like infections, inflammation, chemotherapy or radiation, the hematopoietic system quickly adapts by a process termed "emergency" or "stress" hematopoiesis. For instance, switches from steady state to emergency granulopoiesis or emergency erythropoiesis have been described in response to infection or bleeding. We recently identified, both in human and murine erythroid progenitors, a functional cell-autonomous serotonergic network with pro-survival and proliferative functions. Furthermore, pharmacologic restoration of serotonin levels using selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, a common antidepressant, was demonstrated to rescue the anemic phenotype in mice models. Here, we hypothesized that serotonin also has a role on other hematopoietic lineages, and that the serotonergic system could be a valuable therapeutic target in radiation or chemotherapy-induced cytopenia. Moreover, as our previous work suggested a cross-talk between serotonin and erythropoietin, we postulate that serotonin could act in cooperation with known hematopoietic growth factors. Material and method. For mice models, we submitted C57BL/6 wild-type 8-10 weeks old mice to sub-lethal irradiation and monitored hematopoietic recovery through complete blood counts. We compared mice treated with fluoxetine administrated orally (~ 20 mg/kg/day in drinking water) to a control group, with or without hematopoietic growth factors. For the retrospective human cohort, we used a computerized database to identify patients who underwent autologous hematopoietic stem cell transplantation (ASCT) in the adult hematology department of Necker hospital between 2008 and 2018. We compared 22 patients treated with an SSRI to 66 controls, matched according to number of injected CD34+ cells/kg, age, sex, conditioning chemotherapy, pathology, depth of response before transplantation, previous lines of chemotherapy, and year of transplantation. The study was conducted according to the Declaration of Helsinki. Results. First, we confirmed that, following sub-lethal irradiation, pharmacologic restoration of 5-HT levels in mice using fluoxetine improved normalization of the erythroid lineage (at day 17 post-irradiation, mean hemoglobin was 8.1 versus 2.8 g/dL in the fluoxetine versus control group (p=0.0002)). Second, the data revealed that the use of SSRI lead to a more rapid restoration of the leukocytes and platelets levels (at day 17 post-irradiation, mean leukocyte level was 1740 versus 314/mm3 (p<0.0001) and mean platelet level was 216 versus 43/mm3 (p=0.002) in the fluoxetine versus control group, respectively). Third, we observed an additive effect between fluoxetine and Granulocyte-Colony Stimulating Factor (G-CSF) on the recovery of the three myeloid lineages (at day 17 post-irradiation, mean hemoglobin was 10.5 versus 4.0 g/dL (p<0.0001), mean leukocyte level was 2900 versus 900/mm3 (p<0.0001) and mean platelet level was 308 versus 84/mm3 (p=0.0009) in the fluoxetine + G-CSF versus control group, respectively). Finally, analysis of the in vivo murine model under steady state condition showed that without any hematopoietic stress, fluoxetine did not impact hematopoiesis. In human, analysis of the retrospective ASCT cohort demonstrated that patients treated with SSRI had a more rapid neutrophil recovery than matched control patients (mean duration of neutropenia <500/mm3 was 12.2 days in the SSRI group and 14.26 days in the control group, p=0.0216). SSRI therapy was not associated with a higher rate or quicker relapses of underlying malignant hemopathy: mean progression free survival was 36 months in both groups. Conclusion. In this work, we report a previously unknown role of SSRI in the hematopoietic recovery of cytopenia, both after sub-lethal irradiation in mice and after autologous hematopoietic stem cell transplantation in human. We also observed a significant cooperation between SSRI and G-CSF on the three myeloid lineages. We propose that the serotonergic system could be a valuable therapeutic target in stress hematopoiesis such as in therapy-induced aplasia in patients. Disclosures Hermine: AB Science: Consultancy, Equity Ownership, Honoraria, Research Funding; Celgene: Research Funding; Novartis: Research Funding. OffLabel Disclosure: Fluoxetine is a selective serotonin reuptake inhibitor for oral administration. It is an antidepressant approved for major depressive disorder, obsessive compulsive disorder, bulimia nervosa and panic disorder. We believe its role on serotonin can improve hematopoiesis.

scholarly journals Ex vivo expansion of human hematopoietic stem and progenitor cells

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6083-6090 ◽  
Author(s):  
Ann Dahlberg ◽  
Colleen Delaney ◽  
Irwin D. Bernstein
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Growth Factors ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

AbstractDespite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood–derived stem cell. Finally, we discuss some of the challenges still facing this field.

scholarly journals Estrogens Enhance Human Hematopoietic Stem Cell Engraftment in a Xenogenic Transplantation Model

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2042-2042
Author(s):  
Sara Fañanas-Baquero ◽  
Israel Orman ◽  
Federico Becerra Aparicio ◽  
Silvia Bermudez de Miguel ◽  
Jordi Garcia Merino ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Short Term ◽  
Myeloablative Conditioning ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
Equity Ownership

Abstract Hematopoietic Stem Cells (HSCs) is a rare cell population that sits atop a hierarchy of progenitors that become progressively restricted to several or a single blood lineage. HSCs are capable of self-renewal and multipotent differentiation to all blood cell lineages. HSCs are crucial in the maintenance of lifelong production of all blood cells. HSCs are highly regulated to maintain homeostasis through a delicate balance between quiescence, self-renewal and differentiation. However, this balance is altered during the hematopoietic recovery after Hematopoietic Stem Cell Transplantation (HSCT). HSCT is routinely used to reconstitute hematopoiesis after myeloablation, being the most commonly-used cell therapy. HSCT efficacy and multilineage reconstitution can be limited by inadequate HSC number, poor homing, engraftment, or limited self-renewal. Recent evidence indicates that estrogens are involved in regulating the hematopoietic system homeostasis. Estrogens are the primary female sex hormones and are responsible for controlling many cellular processes including growth, differentiation and function of the reproductive system. However, estrogens have also been proposed to regulate HSCs. b-Estradiol (E2) was shown to promote the cell cycle of HSCs and multipotent progenitors (MPPs) and increase erythroid differentiation in females (1). On the other hand, tamoxifen reduces the number of MPPs and short-term HSCs but activates proliferation of long-term HSCs (2). The potential clinical application of estrogens in HSCT mainly derives from the possibility that these drugs may enhance the engraftment of transplanted HSCs, thus reducing side effects associated to myeloablative conditioning. Here, we show that a short-term treatment of immunodeficient mice transplanted with hCD34+ cells with estrogens such as E2 and estetrol (E4) improves human hematopoietic engraftment. Fifty-thousand cord blood CD34+ cells (CB-CD34+) were transplanted into sublethally irradiated immunodeficient NSG mice. Three days after transplantation, mice were treated for four days with daily subcutaneous doses of E2, E4 or vehicle. Human hematopoietic engraftment was evaluated in the BM of transplanted mice at four months later. E2 and E4 estrogens increased the proportion of hCD45+ cells 1.8-fold and 2.4-fold as compared to values determined in control mice, without modifying the proportion of myeloid and lymphoid lineages. Significantly, animals treated with either estrogen had significantly higher levels of human hematopoietic progenitors (hCD45+CD34+). To study the engraftment of long-term engraftment HSCs in transplanted mice, human CD45+ cells from primary recipients were sorted and transplanted in secondary NSG recipients. Three months after transplants, the proportion of human hematopoietic cells in secondary recipients was also higher when primary recipients were treated with E2 or E4 than in vehicle-treated animals. Improved engraftments associated to the administration of E2 or E4 estrogens were confirmed when very low doses of CB-CD34+ cells were transplanted (5x103 hCD34+/mouse) in recipients of either sex. Collectively, our data support a new application of estrogens to improve the hematopoietic recovery after HSCT. This application may have particular relevance to enhance the hematopoietic recovery after myeloablative conditioning and when limiting numbers of HSCs are available. Disclosures Bueren: Rocket Pharmaceuticals Inc: Consultancy, Equity Ownership, Patents & Royalties, Research Funding. Segovia:Rocket Pharmaceuticals Inc: Consultancy, Equity Ownership, Patents & Royalties, Research Funding.

Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1784-1789 ◽  
Author(s):  
Barbara Varnum-Finney ◽  
Carolyn Brashem-Stein ◽  
Irwin D. Bernstein
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Cell Fate ◽  
Stem Cell Differentiation ◽  
Myeloid Differentiation ◽  
Hematopoietic Growth Factors ◽  
Hematopoietic Stem ◽  
Notch Ligand ◽  
Gm Csf ◽  
Macrophage Colony

We investigated whether combined signaling induced by engineered Notch ligands and hematopoietic growth factors influences hematopoietic stem-cell differentiation. We show that incubation of murine marrow precursors with Delta1ext-IgG, a Notch ligand consisting of the Delta1 extracellular domain fused to the Fc portion of human immunoglobulin G1 (IgG1), and growth factors stem cell factor (SCF), interleukin 6 (IL-6), IL-11, and Flt3-l inhibited myeloid differentiation and promoted a several-log increase in the number of precursors capable of short-term lymphoid and myeloid repopulation. Addition of IL7 promoted early T-cell development, whereas addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) led to terminal myeloid differentiation. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic cell fate and suggest the usefulness of Notch ligand in increasing hematopoietic precursor numbers for clinical stem-cell transplantation.

scholarly journals Impact of the Use of Bendamustine Immediately before the Collection of Hematopoietic Stem Cells in Lymphoma. a Study By the Geltamo Group

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1771-1771
Author(s):  
Mariana Bastos-Oreiro ◽  
Javier Anguita ◽  
José Fernández ◽  
Ana Pilar Gonzalez ◽  
Raul Córdoba ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Research Funding ◽  
Median Number ◽  
Control Group ◽  
First Line ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Number Of Cycles ◽  
Pbsc Mobilization

Abstract Introduction: Bendamustine is a hybrid alkylating agent with high efficacy in different haematological malignancies, especially for lymphomas. Data about the capacity of peripheral blood stem cell (PBSC) mobilization or a possible stem cell toxicity after the use of bendamustine are unclear, with sufficient number of PBSC after bendamustine- rituximab (B-R) combination used in first line but with scarce information in relapse, especially with the use of bendamustine immediately before mobilization. The aim of this study was to evaluate the influence on PBSC mobilization of bendamustine as the last previous regimen used before the collection of PBSC. Methods: This is a retrospective, multicentre study, which includes patients from 8 different GELTAMO centres in Spain. Forty-eight lymphoma patients who received bendamustine followed immediately by stem cell mobilization (SCM) were included. A single-centre control group of consecutive patients was included, matched by histology, age and number of previous lines; HIV+ patients were excluded. Results: We included 83 patients, 45 in the bendamustine group and 38 in the control group. Table 1 shows patient´s characteristics. Both groups are adequately balanced. No patients received previous lenalidomide, and none patient had previous transplant. In the bendamustine group, the median number of cycles administered was 4 (range 2-6). In 8 patients of the bendamustine group and 12 in the control group the mobilization was programmed after first-line treatment. In the remaining cases, mobilizations were performed after 1 st or 2 nd relapse treatment. In most of the patients, the mobilization regimen was performed only with G-CSF, although 7 patients in the control and 3 patients in bendamustine groups received alternative regimens such as ESHAP, DHAP or ICE. Ten patients in the bendamustine group received plerixafor as part of the 1 st attempt mobilization regimen. Median number of apheresis with the first attempt of mobilization was 1.5 in the bendamustine group vs 1.3 in the control group. In bendamustine group 8 patients didn't go to apheresis due to a low pre-mobilization CD34+ cell count in peripheral blood, compared with 2 patients in control group. Median pre-mobilization CD34+ cells and median number of mobilized CD34 cells obtained was significative lower with in bendamustine group (Table 1). Moreover, 10 patients in this group didn't mobilized with 1 st attempt (and in 4 of them and neither with the second mobilization attempt), compared with only 2 in the control group. Mobilization failure in the bendamustine group was more frequent in certain lymphoma subtypes (among the 10 failures, HL and FL were the most frequent, 40%, p=0.07, and 50%, p=0.051 respectively), and was also associated with number of previous lines of therapy (HR 4,1; p= 0.041), since 90% of the failures were patients mobilized at relapse, and only 1 as 1st line consolidation. No relationship was found between stage, doses, or number of cycles of bendamustine administered. Conclusion: Our results show that the collection of sufficient numbers of PBSC could be affected by the use of bendamustine immediately prior to mobilization, especially in more pre-treated patients. We continue working on expanding our series to confirm these results. Figure 1 Figure 1. Disclosures Bastos-Oreiro: Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Salar: Roche: Consultancy, Speakers Bureau; Gilead: Research Funding; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Sancho: Roche, Janssen, Celgene-BMS, Gilead, Novartis, Takeda: Honoraria, Speakers Bureau; Roche, Janssen, Celgene-BMS, Gilead, Novartis, Incyte, Beigene: Speakers Bureau.

scholarly journals Marrow- and spleen-seeding efficiencies of all murine hematopoietic stem cell subsets are decreased by preincubation with hematopoietic growth factors

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2598-2606 ◽  
Author(s):  
JC van der Loo ◽  
RE Ploemacher
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Growth Factors ◽  
Hematopoietic Stem ◽  
Murine Hematopoietic Stem Cell ◽  
Seeding Efficiency

The cobblestone-area forming cell (CAFC) assay permits a direct measurement of the seeding of primitive and more mature murine hematopoietic stem cell subsets by comparing the number of CAFC in the original transplant with the number of CAFC retrieved from bone marrow (BM) and spleen after transplantation. We found no differences in seeding efficiency between the more mature and primitive CAFC subsets, nor between seeding efficiencies of stem cells from low-density (LD) fractions of normal and day-6 post-5-fluorouracil BM. The data show that 18% to 20% of all intravenously transplanted stem cell subsets seed to the BM, whereas 8% to 10% seed to the spleen. In addition, similar seeding efficiencies were found for day-12 spleen colony-forming unit (CFU-S-12) as was determined by retransplantation. Previously, it has been reported that a 2- to 3-hour preincubation of BM with interleukin-3 (IL-3) enhances the in vivo repopulating ability of a graft. To test whether hematopoietic growth factors affected this increased engraftment by enhancing the seeding of the transplanted marrow, we assessed the 16- to 18-hour seeding efficiency of short- and long-term in vivo repopulating stem cell subsets to BM and spleen using the CAFC assay, after preincubation with or without hematopoietic growth factors. A 2- to 3-hour preincubation with IL-3, or a combination of IL-3, IL-12, and steel factor, at 37 degrees C, led to a substantial decrease in seeding compared with control (which was kept on ice) of all hematopoietic subsets measured, both in spleen and BM. In concert with these data, the long-term in vivo repopulating ability of growth-factor incubated BM was also decreased when compared with control. In conclusion, we have been unable to observe a beneficial effect of growth factor preincubation on the repopulating ability of a graft.

scholarly journals Reversible TET Inhibitor As a Hematopoietic Stem Cell Booster: A Novel Strategy to Improve Stem Cell Function

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2472-2472
Author(s):  
Sunisa Kongkiatkamon ◽  
Yihong Guan ◽  
Anand Tiwari ◽  
Phillip J Maciejewski ◽  
Dale Grabowski ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Board Of Directors ◽  
Suspension Cultures ◽  
Hematopoietic Growth Factors ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Wide Range

Hematopoietic stem cells (HSCs) are responsible for the adaptation capacity in times of need but are also subjected to disease processes, natural or iatrogenic damage, and age-related attrition. The latter can lead to deficient production, decreased compensatory capacity and degenerative diseases such as MDS. In childhood, hereditary BMF predominates but increasingly with age, acquired idiopathic AA is a leading cause of HSC failure. Throughout life iatrogenic cases and cumulative exposures to environmental toxicities may lead to failure of the HSC compartment. Pharmacologic HSC boosters capable of expanding HSCs would have a wide range of clinical applications in acquired and inherited BMF states, including reconstitution of exhausted hematopoiesis after chemotherapy, aging, or HSC grafting. Currently, hematopoietic growth factors (HGF) are used but lead to progenitor rather than HSC expansion despite their success in clinical application. Depletion of TET2 in murine models leads to impairment of cellular differentiation and increases the proportion of HSCs and progenitors suggesting that TET2 is a key regulator of hematopoietic homeostasis and HSC self-renewal. Alterations of TET2 via somatic mutations and/ or deletion are frequent in MDS whereby HSC and progenitor expansion may be a key component of neoplastic evolution. We hypothesized that chemical agents reversibly inhibiting TET2 activity might phenocopy HSC expansion due to mutations and be applied as HSC boosters. Using structure guided approaches, we designed, synthesized and subsequently optimized bioavailable TET inhibitors (TETi). Among them, the one of the most effective TETi, named TETi76, showed dose-dependent inhibitory activity against TET dioxygenases in in vitro cell-free and cell culture systems with 5hmC production as a read out. We developed esterified forms of TETi76 and used in our cellular experimental models. Esterified TETi is bioavailable and non-toxic to normal bone marrow (BM) cells in therapeutically effective doses. Treatment of TETi76 resulted in a 44+15% and 42+17% increase in the clonogenic potential of human and murine BM cells consistent with the proliferative advantage gained by loss of TET activity in HSCs. We then performed serial replating experiments to determine the effect of TET inhibition on immature hematopoietic progenitor cells. Over 3 consecutive passages, TETi76 treatment prolonged the durability and capacity of human HSCs to maintain colony-forming cells (155+24 vs.107+14 colonies per 1x105 P1 cells). As long-term culture initiating cells (LTC-IC) are the best in vitro surrogates of HSCs, we also investigated the effect of TETi76 in LTC-IC cultures (n=3). The weekly addition of 1μM-TETi76 resulted in nearly 2-fold increase in LTC-IC numbers at the end of the culture (116±27 vs. 64 ±26 colonies per 2x106 P1 cells, p=.011). Expansion of grafts e.g., in the setting of umbilical cord HSC transplant (UCHSC) could be an important medical area of application of TETi76. We performed suspension cultures (n=3) with an optimal cocktail of hematopoietic growth factors (HGF) in the presence or absence of TETi76 (1μM). In control cultures, total cellular output peaked on day 14, but in the presence of TETi, growth continued beyond day 28. Cumulatively, total cellular output per 106 input was 27+2.61 x106cells/mL in control cultures and 32+0.642 x106 cells/mL in TETi treated cultures on day 28. CD34+ cell output was significantly higher in cultures treated with TETi vs. vehicle (2.5x105vs. 0.9X106)CD34+ cells per 1x104 CD34+ cell input). Similar effects were observed in murine BM suspension cultures. BM cells from C57BL/6 mice (n=3) were supplemented with HGF± TETi76 (1μM). TETi treatment led to a 5-fold HSC expansion compared to vehicle treated cells at 20 days of culture. The effect of TETi76 was reversed by treatment with ascorbic acid (50 μM), a known TET activator. Cumulatively our in vitro results suggest that the presence of TETi prevents exhaustion of immature cells, observed with growth factor driven expansion. In summary, our study indicates that novel agents modulating TET activity prevent exhaustion of HSC and may help expand the HSC in vitro. In vivo experiments examining the effects of TETi on hematopoietic recovery following radiation-induced aplasia, and competitive transplant experiments of grafts exposed in vivo and in vitro to TETi are underway. Disclosures Sekeres: Millenium: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Novartis: Consultancy; Alexion: Consultancy.

Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gizem Guner Ozenen ◽  
Serap Aksoylar ◽  
Damla Goksen ◽  
Salih Gozmen ◽  
Sukran Darcan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Life Quality ◽  
Control Group ◽  
Hematopoietic Stem

Abstract Objectives The early and late complications after hematopoietic stem cell transplantation (HSCT) determine the patients’ prognosis and life quality. We aim to determine the metabolic syndrome development frequency after HSCT in children to find out the risk factors and compare them with healthy adolescents. Methods Thirty-six children who underwent HSCT at least two years ago were analyzed prospectively and cross-sectionally. Our study included 18 healthy children between the ages of 11 and 17 as a control group. All of the cases were assessed in terms of metabolic syndrome (MS) through the use of Modified WHO Criteria. Results The patients’ median age was 10.6 (5.1–17) years, the median time of follow-up after HCST was 4.1 (2–13.5) years and 70% were male. Two cases were diagnosed with MS (5.6%). When considered in terms of the sub-components of MS, 2 cases (5.6%) were found to have obesity, 17 cases (47%) abnormal glucose tolerance, 11 cases (30.7%) dyslipidemia, and 3 cases (8.6%) hypertension. The MS rate was not different when compared with the 11–17 year-old healthy control group (0 vs. 11%, p=0.48). Myeloablative conditioning regimen (65 vs. 20%) and the increased age at which HSCT was performed were considered to be risk factors in terms of insulin resistance (p=0.025 and 0.002). Conclusions Age and conditioning regimens were found to be the risk factors for insulin resistance development. The long-term follow-up of the cases who had undergone HSCT in childhood in terms of MS and its sub-components is important in order to increase life quality.

The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis

2017 ◽  
Vol 53 ◽  
pp. S105
Author(s):  
Alexander Gerbaulet ◽  
Kristina Schoedel ◽  
Mina Morcos ◽  
Thomas Zerjatke ◽  
Ingo Roeder ◽  
...  
Keyword(s):  
Stem Cell ◽  
Steady State ◽  
Hematopoietic Stem Cell ◽  
Cell Population ◽  
Stem Cell Population ◽  
Hematopoietic Stem
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