Bone Marrow Transplantation Induces Normoglycemia in a Type 2 Diabetes Mellitus Murine Model

Flaquer, Maria; Franquesa, M.; Barquinero, Jordi; Lloberas, Núria; Gutiérrez, C.; Torrás, Joan; Grinyó, J.M.; Cruzado, Josep M.

doi:10.1016/j.transproceed.2009.06.034

Cited by 10 publications

(9 citation statements)

References 9 publications

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“…In contrast, the db/db mice treated with IBM–BMT + TT showed normal blood glucose levels even 7 weeks after the treatment. These data are inconsistent with a previous report: Cruzado JM et al reported that db/db mice treated with BMT alone showed normoglycemia even 10 weeks after the treatment [44]. …”

Section: Discussioncontrasting

confidence: 99%

Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow–bone marrow transplantation plus concurrent thymic transplantation

Abraham

Vanella

et al. 2010

Journal of Autoimmunity

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There is increasing evidence that both autoimmune and autoinflammatory mechanisms are involved in the development of not only type 1 diabetes mellitus (T1 DM), but also type 2 diabetes mellitus (T2 DM). Our laboratory has focused on this concept, and in earlier efforts replaced the bone marrow cells (BMCs) of leptin receptor-deficient (db/db) mice, an animal model of T2DM, with those of normal C57BL/6 (B6) mice by IBM–BMT. However, the outcome was poor due to incomplete recovery of T cell function. Therefore, we hypothesized that intra-bone marrow–bone marrow transplantation plus thymus transplantation (IBM–BMT + TT) could be used to treat T2 DM by normalizing the T cell imbalance. Hence we addressed this issue by using such dual transplantation and demonstrate herein that seven weeks later, recipient db/db mice manifested improved body weight, reduced levels of blood glucose, and a reduction of plasma IL-6 and IL-1 β. More importantly, this treatment regimen showed normal CD4/CD8 ratios, and increased plasma adiponectin levels, insulin sensitivity, and the number of insulin-producing cells. Furthermore, the expression of pancreatic pAKT, pLKB1, pAMPK and HO-1 was increased in the mice treated with IBM–BMT + TT. Our data show that IBM–BMT + TT treatment normalizes T cell subsets, cytokine imbalance and insulin sensitivity in the db/db mouse, suggesting that IBM–BMT + TT is a viable therapeutic option in the treatment of T2 DM.

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Section: Discussioncontrasting

confidence: 99%

Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow–bone marrow transplantation plus concurrent thymic transplantation

Abraham

Vanella

et al. 2010

Journal of Autoimmunity

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“…Groups of 6 week old WT and NOX2 -/- mice were irradiated (9.0 Gy) for 10 minutes according to Flaquer and collaborators [22]. Lead shields were used to protect the head during the radiation.…”

Section: Methodsmentioning

confidence: 99%

Requirement of NOX2 Expression in Both Retina and Bone Marrow for Diabetes-Induced Retinal Vascular Injury

Rojas

Zhang

et al. 2013

PLoS ONE

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ObjectiveDiabetic retinopathy, a major cause of blindness, is characterized by increased expression of vascular endothelial growth factor (VEGF), leukocyte attachment to the vessel walls and increased vascular permeability. Previous work has shown that reactive oxygen species (ROS) produced by the superoxide generating enzyme NOX2/NADPH oxidase play a crucial role in the vascular pathology. The aim of this work was to identify the cellular sources of the damaging NOX2 activity by studies using bone marrow chimera mice. MethodsBone marrow cells were collected from the femurs and tibias of wild type and NOX2 deficient (NOX2-/-) donor mice and injected intravenously into lethally irradiated NOX2-/- and wild type recipients. Following recovery from radiation, mice were rendered diabetic by streptozotocin injections. The following groups of bone marrow chimeras were studied: non-diabetic WT→WT, diabetic WT→WT, diabetic WT→NOX2-/-, diabetic NOX2-/-→WT. After 4 weeks of diabetes, early signs of retinopathy were examined by measuring ROS, expression of VEGF and ICAM-1, leukocyte attachment to the vessel wall and vascular permeability. ResultsThe retinas of the diabetic WT→WT chimeras showed significant increases in ROS as compared with the non-diabetic chimeras. These diabetes-induced alterations were correlated with increases in expression of VEGF and ICAM-1, leukocyte adhesion and vascular permeability. Each of these diabetes-induced alterations were significantly attenuated in the diabetic WT→NOX2-/- and NOX2-/-→WT chimera groups (p<0.05). ConclusionNOX2-generated ROS produced by both bone marrow-derived cells and resident retinal cells contribute importantly to retinal vascular injury in the diabetic retina. Targeting NOX2 in bone marrow and/or retinal cells may represent a novel therapeutic strategy for the treatment/prevention of vascular injury in the diabetic retina.

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“…On the contrary, transplantation of BM isolated from NOD mice transfer type 1 diabetes into non-disease recipient mice [68,72,73]. In contrast, after transplantation of wild type-BM in db/ db mice, most of the animals remained diabetic [74]. The role of BM cells in the etiology of metabolic disorders has been further decrypted by using transgenic mice harboring a genetic alteration in a relevant pathway as donor cells.…”

Section: Metabolic Disorders and Bone Marrow Hematopoiesismentioning

confidence: 99%

Immuno-metabolism and adipose tissue: The key role of hematopoietic stem cells

et al. 2016

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Bone Marrow Transplantation Induces Normoglycemia in a Type 2 Diabetes Mellitus Murine Model

Cited by 10 publications

References 9 publications

Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow–bone marrow transplantation plus concurrent thymic transplantation

Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow–bone marrow transplantation plus concurrent thymic transplantation

Requirement of NOX2 Expression in Both Retina and Bone Marrow for Diabetes-Induced Retinal Vascular Injury

Immuno-metabolism and adipose tissue: The key role of hematopoietic stem cells

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