Disposable No Longer: The Spleen Holds a Reservoir of Stem Cells

Faustman, Denise L.; Giesecke, Claudia; Davis, Miriam; Kühtreiber, Willem M.; Tran, Simon D.; Dörner, Thomas; Ley, Eric J.

doi:10.4172/2157-7633.1000219

Cited by 3 publications

(2 citation statements)

References 63 publications

(91 reference statements)

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“…Interestingly, we also observed an increase in CD3 + /CD4‐/CD8‐ T cells, which has recently been suggested to potentially be a regulatory cell (Miyagawa, Okiyama, Villarroel, & Katz, ). Administration of IL‐10 did not affect blood glucose levels, nor did it offset the splenic atrophy seen in diabetic mice (Faustman, Giesecke, Davis, Kühtreiber, & Tran, ) (Figure S7).…”

Section: Resultsmentioning

confidence: 96%

Brief exposure to hyperglycemia activates dendritic cells in vitro and in vivo

Thomas

Dong

Beskid

et al. 2019

Journal Cellular Physiology

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Dendritic cells are key players in regulating immunity. These cells both activate and inhibit the immune response depending on their cellular environment. Their response to hyperglycemia, a condition common amongst diabetics wherein glucose is abnormally elevated, remains to be elucidated. In this study, the phenotype and immune response of dendritic cells exposed to hyperglycemia were characterized in vitro and in vivo using the streptozotocin‐induced diabetes model. Dendritic cells were shown to be sensitive to hyperglycemia both during and after differentiation from bone marrow precursor cells. Dendritic cell behavior under hyperglycemic conditions was found to vary by phenotype, among which, tolerogenic dendritic cells were particularly sensitive. Expression of the costimulatory molecule CD86 was found to reliably increase when dendritic cells were exposed to hyperglycemia. Additionally, hydrogel‐based delivery of the anti‐inflammatory molecule interleukin‐10 was shown to partially inhibit these effects in vivo.

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Section: Resultsmentioning

confidence: 96%

Brief exposure to hyperglycemia activates dendritic cells in vitro and in vivo

Thomas

Dong

Beskid

et al. 2019

Journal Cellular Physiology

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“…Our findings support the hypothesis that G-CSF mobilizes at least two distinct and non-overlapping populations of stem cells, CD34 + hematopoietic stem cells from bone marrow and Hox11 + stem cells from the spleen. The very dramatic mobilization of splenic stem cells suggests that G-CSF's well-known advantage over bone marrow for stem cell transplantation protocols may be due to two stem cell populations, including the less differentiated stem cells of the spleen with broad hematopoietic reconstitution abilities [9,11,12,16,17]. Indeed, prior to this data it was viewed that the common occurrence of splenomegaly after G-CSF treatment was an adverse outcome that could on rare occasions result in splenic rupture; instead it may well be the case the G-CSF is mobilizing immature stem cells, mature neutrophils and other beneficial splenic populations [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

The Spleen Contributes Stem Cells to Peripheral Blood Stem Cell Transplants

Mera¹

2014

J Stem Cell Res Ther

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The spleen assumes a major role in blood glucose regulation in type 1 diabetes patients treated with BCG

Dias,

Fu,

Luck

et al. 2024

Sci Rep

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The Bacillus Calmette-Guérin (BCG) vaccine, which has been used for > 100 years to prevent tuberculosis, is well-established for bladder cancer treatment, and under study for neurological and autoimmune diseases. In patients with type 1 diabetes (T1D), BCG vaccinations have been shown in randomized clinical trials to gradually lower blood sugar to near normal levels. This effect appears to be driven by a BCG-induced shift in lymphoid cells’ glucose metabolism from oxidative phosphorylation to aerobic glycolysis. The latter is a state of high glucose utilization that draws more glucose from the blood. Apart from blood, it is unknown whether BCG establishes residence in any organs and alters their glucose metabolism. In this two-year-long clinical trial in type 1 diabetics, we use positron emission tomography (PET) and x-ray computed tomography (CT) to map organs that increase their uptake of the glucose analogue 18 F-fluorodeoxyglucose ( 18 F-FDG) before versus after BCG vaccinations. We also injected BALB/c mice with BCG to test for the presence of BCG in various organs. Results from both studies point to the spleen as the dominant site for glucose uptake and BCG residence. The human spleen is significant because its 47% increase in 18 F-FDG uptake by a large population of lymphocytes and monocytes might help to explain BCG’s systemic lowering of blood glucose to near normal levels. Findings suggest that the spleen, triggered by BCG, assumes a critical role in systemic glucose regulation in the absence of a functional pancreas.

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Disposable No Longer: The Spleen Holds a Reservoir of Stem Cells

Cited by 3 publications

References 63 publications

Brief exposure to hyperglycemia activates dendritic cells in vitro and in vivo

Brief exposure to hyperglycemia activates dendritic cells in vitro and in vivo

The Spleen Contributes Stem Cells to Peripheral Blood Stem Cell Transplants

The spleen assumes a major role in blood glucose regulation in type 1 diabetes patients treated with BCG

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