Antiproliferative effect of mycophenolate mofetil on cultured human Tenon fibroblasts

Heinz, Carsten; Hudde, Tobias; Heise, Kerstin; Steuhl, Klaus‐Peter

doi:10.1007/s00417-002-0452-4

Cited by 21 publications

(12 citation statements)

References 42 publications

(37 reference statements)

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“…Similar to mPRED, MMF caused a significant inhibition of cell proliferation, and this is in line with previously published in vitro data [39,43,44]. The concentration of 1 mg?L -1 MMF corresponds to the target whole-blood level for transplant patients [45].…”

Section: Figuresupporting

confidence: 77%

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Hostettler¹,

Gerull²,

Lardinois³

et al. 2013

European Respiratory Journal

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Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS).Cells were isolated from surgical lung biopsies of eight HSCT patients with BOS. Proliferation was assessed by [ 3 H]-thymidine incorporation. Biopsies revealed constrictive bronchiolitis obliterans in three patients and lymphocytic bronchiolitis in five patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Costimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1 of patients with bronchiolitis obliterans was unchanged.Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMF in vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT. @ERSpublications Calcineurin inhibitor-free regimens need further evaluation in bronchiolitis obliterans after stem cell transplantation

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Section: Figuresupporting

confidence: 77%

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Hostettler¹,

Gerull²,

Lardinois³

et al. 2013

European Respiratory Journal

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“…MPA leads to a five times more effective inhibition of IMPDH type II, which is mainly expressed in activated lymphocytes, but it also inhibits the type I isoform expressed in most other cell types [16] . This may also cause a dose-dependent inhibition of fibroblast proliferation, as has been shown in rat kidneys [17] , cultures of human Tenon cells of the eye [18] as well as in dermal fibroblast cultures [19] . A group from Heidelberg reported recently that MPA administration to cultured human fibroblasts resulted in a downregulation of cytoskeletal proteins, a rearrangement of the cytoskeleton and impaired migrational capacity.…”

Section: Discussionmentioning

confidence: 98%

Impact of Mycophenolate Mofetil on Wound Complications and Lymphoceles after Kidney Transplantation

Lopau¹,

Syamken²,

Rubenwolf

et al. 2010

Kidney Blood Press Res

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Background/Aims: Despite improved efficacy, modern immunosuppressive agents may show unanticipated side effects. In this study we investigated the possible interactions of mycophenolate mofetil (MMF) with wound healing and lymphocele formation. Methods: We conducted a retrospective single-center analysis in 144 patients receiving a cyclosporine A-based immunosuppression with prednisolone and either MMF (n = 77) or azathioprine (AZA, n = 77). Endpoints were incidences of lymphocele formation and non-primary wound healing during 6 months’ follow-up. Results: AZA-treated patients had more rejection episodes and consecutively more steroid pulses, both being potential risk factors for endpoints. No graft was lost in any group and graft function was comparable. AZA patients demonstrated a trend for more frequent wound infections. Fluid accumulation around the graft, however, was more frequent in the MMF group (OR = 2.6; p = 0.03). Consequently, more drainage maneuvers (17 vs. 5 interventions) and sclerotherapies (8 vs. 0 interventions) were undertaken in MMF patients. Pre-assigned risk factors for lymphoceles reported before did not differ between both cohorts; patients experiencing acute rejection episodes had even less symptomatic lymphoceles (n = 23). Conclusion: We found a possible relationship between the administration of MMF and lymphocele formation. To avoid the hazard of reinterventions, the prolongation of hospitalization and impairment of graft function, it requires awareness and attention in patients treated with this immunosuppressant.

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“…In vitro studies showed that MPA has a direct antiproliferative effect and inhibits cell activation in cultures of mesangial cells, the fibrogenic cells within glomeruli [11,12]. Other studies report that MPA is able to inhibit the proliferation of tenon fibroblasts and vascular smooth muscle cells, which are main players in fibrotic processes in the eye and during atherosclerosis, respectively, [13,14]. This may imply that MPA can also act on HSC.…”

Section: Introductionmentioning

confidence: 92%

Studies on the targeted delivery of the antifibrogenic compound mycophenolic acid to the hepatic stellate cell

Greupink¹,

Bakker²,

Reker‐Smit³

et al. 2005

Journal of Hepatology

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Antiproliferative effect of mycophenolate mofetil on cultured human Tenon fibroblasts

Cited by 21 publications

References 42 publications

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Impact of Mycophenolate Mofetil on Wound Complications and Lymphoceles after Kidney Transplantation

Studies on the targeted delivery of the antifibrogenic compound mycophenolic acid to the hepatic stellate cell

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