| 1. |
- Adolfsson, Jörgen, et al.
(författare)
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Identification of Flt3(+) lympho-myeloid stem cells lacking erythro-megakaryocytic potential: A revised road map for adult blood lineage commitment
- 2005
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Ingår i: Cell. - : Elsevier (Cell Press). - 0092-8674 .- 1097-4172. ; 121:2, s. 295-306
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Tidskriftsartikel (refereegranskat)abstract
- All blood cell lineages derive from a common hematopoietic stem cell (HSC). The current model implicates that the first lineage commitment step of adult pluripotent HSCs results in a strict separation into common lymphoid and common myeloid precursors. We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell potentials but in contrast to Lin-Sca-1(+)ckit(+)Flt3(-) HSCs fail to produce significant erythroid and megakaryocytic progeny. This distinct lineage restriction site is accompanied by downregulation of genes for regulators of erythroid and megakaryocyte development. In agreement with representing a lymphoid primed progenitor, Lin(-)Sca-l(+)c-kit(+)CD34(+)Flt3(+) cells display upregulated IL-7 receptor gene expression. Based on these observations, we propose a revised road map for adult blood lineage development.
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| 2. |
- Adolfsson, Jörgen, et al.
(författare)
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Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity
- 2001
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Ingår i: Immunity. - 1074-7613. ; 15:4, s. 659-669
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Tidskriftsartikel (refereegranskat)abstract
- Flt3 has emerged as a potential regulator of hematopoietic stem cells (HSC). Sixty percent of cells in the mouse marrow Lin(-)Sca1(+)c-kit(+) HSC pool expressed flt3. Although single cell cloning showed comparable high proliferative, myeloid, B, and T cell potentials of Lin(-)Sca1(+)c-kit(+)flt3(+) and Lin(-)Sca1(+)c-kit(+)flt3(-) cells, only Lin(-)Sca1(+)c-kit(+)flt3(-) cells supported sustained multilineage reconstitution. In striking contrast, Lin(-)Sca1(+)c-kit(+)flt3(+) cells rapidly and efficiently reconstituted B and T lymphopoiesis, whereas myeloid reconstitution was exclusively short term. Unlike c-kit, activation of flt3 failed to support survival of HSC, whereas only flt3 mediated survival of Lin(-)Sca1(+)c-kit(+)flt3(+) reconstituting cells. Phenotypic and functional analysis support that Lin(-)Sca1(+)c-kit(+)flt3(+) cells are progenitors for the common lymphoid progenitor. Thus, upregulation of flt3 expression on Lin(-)Sca1(+)c-kit(+) HSC cells is accompanied by loss of self-renewal capacity but sustained lymphoid-restricted reconstitution potential.
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| 8. |
- Anderud, Jonas, et al.
(författare)
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Guided bone augmentation using a ceramic space-maintaining device
- 2014
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Ingår i: Oral surgery, oral medicine, oral pathology and oral radiology. - : Elsevier. - 2212-4403 .- 2212-4411. ; 118:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The purpose of this study was to evaluate 3-dimensionally whether vertical bone augmentation can be achieved using a hollow hydroxyapatite space-maintaining device in a rabbit calvarial model. Furthermore, different inner surface topographies, different permeabilities, and different porosities of the ceramic were tested to determine the optimal conditions for bone regeneration.
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| 9. |
- Anderud, Jonas, et al.
(författare)
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Guided bone augmentation using ceramic space-maintaining devices : The impact of chemistry
- 2015
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Ingår i: Clinical, Cosmetic and Investigational Dentistry. - : Nakladatelstvi Lidove noviny. - 1179-1357. ; 7, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to evaluate histologically, whether vertical bone augmentation can be achieved using a hollow ceramic space maintaining device in a rabbit calvaria model. Furthermore, the chemistry of microporous hydroxyapatite and zirconia were tested to determine which of these two ceramics are most suitable for guided bone generation. 24 hollow domes in two different ceramic materials were placed subperiosteal on rabbit skull bone. The rabbits were sacrificed after 12 weeks and the histology results were analyzed regarding bone-to-material contact and volume of newly formed bone. The results suggest that the effect of the microporous structure of hydroxyapatite seems to facilitate for the bone cells to adhere to the material and that zirconia enhance a slightly larger volume of newly formed bone. In conclusion, the results of the current study demonstrated that ceramic space maintaining devices permits new bone formation and osteoconduction within the dome.
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| 10. |
- Bryder, David, et al.
(författare)
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Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation
- 2001
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 194:7, s. 941-952
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Tidskriftsartikel (refereegranskat)abstract
- Multipotent self-renewing hematopoietic stem cells (HSCs) are responsible for reconstitution of all blood cell lineages. Whereas growth stimulatory cytokines have been demonstrated to promote HSC self-renewal, the potential role of negative regulators remains elusive. Receptors for tumor necrosis factor (TNF) and Fas ligand have been implicated as regulators of steady-state hematopoiesis, and if overexpressed mediate bone marrow failure. However, it has been proposed that hematopoietic progenitors rather than stem cells might be targeted by Fas activation. Here, murine Lin(-)Sca1(+)c-kit(+) stem cells revealed little or no constitutive expression of Fas and failed to respond to an agonistic anti-Fas antibody. However, if induced to undergo self-renewal in the presence of TNF-alpha, the entire short and long-term repopulating HSC pool acquired Fas expression at high levels and concomitant activation of Fas suppressed in vitro growth of Lin(-)Sca1(+)c-kit(+) cells cultured at the single cell level. Moreover, Lin(-)Sca1(+)c-kit(+) stem cells undergoing self-renewal divisions in vitro were severely and irreversibly compromised in their short- and long-term multilineage reconstituting ability if activated by TNF-alpha or through Fas, providing the first evidence for negative regulators of HSC self-renewal.
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| 11. |
- Johansson, Lars-Åke, 1950, et al.
(författare)
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Bone Regeneration Using a Hollow Hydroxyapatite Space-Maintaining Device for Maxillary Sinus Floor Augmentation – A Clinical Pilot Study
- 2012
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Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 14:4, s. 575-584
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Background: The mere lifting of the maxillary sinus membrane by implants protruding into the sinus cavity allows the establishment of a void space for blood clot and new bone formation. Purpose: To evaluate bone formation by using a spherical, hollow, and perforated hydroxyapatite space-maintaining device (HSMD) in a two-stage sinus lift procedure where residual alveolar bone height was
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| 12. |
- Malmström, Johan, et al.
(författare)
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Guided bone regeneration using individualized ceramic sheets
- 2016
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Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier BV. - 0901-5027 .- 1399-0020. ; 45:10, s. 1246-1252
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Tidskriftsartikel (refereegranskat)abstract
- Guided bone regeneration (GBR) describes the use of membranes to regenerate bony defects. A membrane for GBR needs to be biocompatible, cell-occlusive, non-toxic, and mouldable, and possess space-maintaining properties including stability. The purpose of this pilot study was to describe a new method of GBR using individualized ceramic sheets to perfect bone regeneration prior to implant placement; bone regeneration was assessed using traditional histology and three-dimensional (3D) volumetric changes in the bone and soft tissue. Three patients were included. After full-thickness flap reflection, the individualized ceramic sheets were fixed. The sites were left to heal for 7 months. All patients were evaluated preoperatively and at 7 months postoperative using cone beam computed tomography and 3D optical equipment. Samples of the regenerated bone and soft tissue were collected and analyzed. The bone regenerated in the entire interior volume of all sheets. Bone biopsies revealed newly formed trabecular bone with a lamellar structure. Soft tissue biopsies showed connective tissue with no signs of an inflammatory response. This was considered to be newly formed periosteum. Thus ceramic individualized sheets can be used to regenerate large volumes of bone in both vertical and horizontal directions independent of the bone defect and with good biological acceptance of the material.
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| 13. |
- Månsson, Robert, et al.
(författare)
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Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors
- 2007
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Ingår i: Immunity. - : Elsevier BV. - 1074-7613 .- 1097-4180. ; 26:4, s. 407-419
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies implicated the existence of adult lymphoid-primed multipotent progenitors (LMPPs) with little or no megakaryocyte-erythroid potential, questioning common myeloid and lymphoid progenitors as obligate intermediates in hematopoietic stem cell (HSC) lineage commitment. However, the existence of LMPPs remains contentious. Herein, global and single-cell analyses revealed a hierarchical organization of transcriptional lineage programs, with downregulation of megakaryocyte-erythroid genes from HSCs to LMPPs, sustained granulocyte-monocyte priming, and upregulation of common lymphoid (but not B and T cell-specific) genes. These biological and molecular relationships, implicating almost mutual exclusion of megakaryocyte-erythroid and lymphoid pathways, are established already in fetal hematopoiesis, as evidenced by existence of LMPPs in fetal liver. The identification of LMPPs and hierarchically ordered transcriptional activation and downregulation of distinct lineage programs is compatible with a model for HSC lineage commitment in which the probability for undergoing different lineage commitment fates changes gradually when progressing from HSCs to LMPPs.
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| 14. |
- Sitnicka Quinn, Ewa, et al.
(författare)
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Key Role of flt3 Ligand in Regulation of the Common Lymphoid Progenitor but Not in Maintenance of the Hematopoietic Stem Cell Pool.
- 2002
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Ingår i: Immunity. - 1074-7613. ; 17:4, s. 463-472
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Tidskriftsartikel (refereegranskat)abstract
- The first lineage commitment step of hematopoietic stem cells (HSC) results in separation into distinct lymphoid and myeloid differentiation pathways, reflected in the generation of common lymphoid and myeloid progenitors (CLP and CMP, respectively). In this report we present the first evidence for a nonredundant regulator of this process, in that adult mice deficient in expression of the flt3 ligand (FL) have severely (10-fold) reduced levels of the CLP, accompanied by reductions in the earliest identifiable B and T cell progenitors. In contrast, CMP and HSC are unaffected in FL-deficient mice. Noteworthy, CLP express high levels of both the flt3 receptor and ligand, indicating a potential autocrine role of FL in regulation of the earliest lymphoid commitment step from HSC.
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| 15. |
- Särnblad, Stefan, 1963-, et al.
(författare)
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Diabetes Mellitus in children with Down's syndrome
- 2007
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Konferensbidrag (refereegranskat)abstract
- Objectives: Children with Down’s syndrome have an increased risk of type 1 diabetes. However, the reports regarding the prevalence of Down’s syndrome in children with diabetes are few. The aim oft his study was to describe the prevalence of Down’s syndrome among children with diabetes in Sweden. Another aim was to describe the insulin treatment regimens and metabolic control in children and adolescents with diabetes and Down’s syndrome.Methods: Data were collected by a questionnaire that was distributed to all paediatric diabetes centres in Sweden. Data on Down’s syndrome in the background population was obtained from the Swedish birth defect registry.Result: 41 out of 43 clinics answered the questionnaire representing 7083 subjects with diabetes. In April 2007, 15 subjects with Down’s syndrome were identified. Median age was 15.6 (range 4.5 –20.0) years, with a median duration of diabetes of 5.0 years. All children were treated with insulin, mainly with multiple insulin injections (10/15). Three children used insulin pump and two children were treated with twice daily insulin injections. One child was also treated with metformin. The median daily insulin dosage was 0.76 U/kg/d (range 0.05 – 1.7 U/kg/d) and HbA1c (Mono-S, upper reference limit 5.3% ) was 6.3 % (range 4.1 – 7.9%). Coeliac disease was reported in 5 and thyroid disease in 8 children. Simultaneous hypothyroidism, diabetes and celiac disease were noted in two children with Down’s syndrome. We identified a prevalence of Down’s syndrome in patients with diabetes of 0.21%,whereas the prevalence of Down’s syndrome in new-born children in the background population is estimated to 0.13%.Conclusion: The prevalence of Down’s syndrome in children with diabetes seems to be increased in Sweden. Intensive insulin therapy is possible in children and adolescence with Down’s syndrome and the metabolic control is often satisfactory. Registry validated studies are needed to confirm our findings
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| 16. |
- Yang, Liping, et al.
(författare)
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Identification of Lin(-)Sca1(+)kit(+)CD34(+)Flt3- short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients
- 2005
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Ingår i: Blood. - Washington : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 105:7, s. 2717-2723
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Tidskriftsartikel (refereegranskat)abstract
- In clinical bone marrow transplantation, the severe cytopenias induced by bone marrow ablation translate into high risks of developing fatal infections and bleedings, until transplanted hematopoietic stem and progenitor cells have replaced sufficient myeloerythroid offspring. Although adult long-term hematopoietic stem cells (LT-HSCs) are absolutely required and at the single-cell level sufficient for sustained reconstitution of all blood cell lineages, they have been suggested to be less efficient at rapidly reconstituting the hematopoietic system and rescuing myeloablated recipients. Such a function has been proposed to rather be mediated by less well-defined short-term hematopoietic stem cells (ST-HSCs). Herein, we demonstrate that Lin(-)Sca1(+)kit(hi)CD34+ short-term reconstituting cells contain 2 phenotypically and functionally distinct subpopulations: Lin(-)Sca1(+)kit(hi)CD34(+)flt3- cells fulfilling all criteria of ST-HSCs, capable of rapidly reconstituting myelopoiesis, rescuing myeloablated mice, and generating Lin(-)Sca1(+)kit(hi)CD34(+)flt3+ cells, responsible primarily for rapid lymphoid reconstitution. Representing the first commitment steps from Lin(-)Sca1(+)kit(hi) CD34(-)flt3- LT-HSCs, their identification will greatly facilitate delineation of regulatory pathways controlling HSC fate decisions and identification of human ST-HSCs responsible for rapid reconstitution following HSC transplantations.
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