Mobilization of Bone Marrow Cells by CSF3 Protects Mice from Bleomycin-Induced Lung Injury

Zhang, Fen; Zhang, Lu; Jiang, Hanshui; Chen, Xueyuan; Zhang, Yuan; Li, Huiping; Zhang, Rong-xuan; Zheng, Hou-Feng; Chu, Junfeng; Chen, Xuejin

doi:10.1159/000328762

Cited by 15 publications

(13 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell culture data have suggested that the loss of the defining differentiation potential of MSCs occurs in a hierarchical manner, whereby the ability for adipogenic differentiation is commonly abolished first prior to the loss of the chondrogenic differentiation potential, finally giving rise to osteogenic precursor cells4243. The observed reduction in the differentiation potential of MSCs may bear therapeutic significance, as previous publications have reported regenerative effects of mobilized endogenous MSCs in bleomycin-induced pulmonary fibrosis4445. In these datasets, pulmonary damage was mostly induced by topical intratracheal instillation of bleomycin, thereby preserving MSCs of other tissues46.…”

Section: Discussionmentioning

confidence: 96%

Mesenchymal stem cells are sensitive to bleomycin treatment

Nicolay

Rühle

Perez

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) have been shown to attenuate pulmonary damage induced by bleomycin-based anticancer treatments, but the influence of bleomycin on the stem cells themselves remains largely unknown. Here, we demonstrate that human bone marrow-derived MSCs are relatively sensitive to bleomycin exposure compared to adult fibroblasts. MSCs revealed increased levels of apoptosis after bleomycin treatment, while cellular morphology, stem cell surface marker expression and the ability for adhesion and migration remained unchanged. Bleomycin treatment also resulted in a reduced adipogenic differentiation potential of these stem cells. MSCs were found to efficiently repair DNA double strand breaks induced by bleomycin, mostly through non-homologous end joining repair. Low mRNA and protein expression levels of the inactivating enzyme bleomycin hydrolase were detected in MSCs that may contribute to the observed bleomycin-sensitive phenotype of these cells. The sensitivity of MSCs against bleomycin needs to be taken into consideration for ongoing and future treatment protocols investigating these stem cells as a potential treatment option for bleomycin-induced pulmonary damage in the clinic.

show abstract

Section: Discussionmentioning

confidence: 96%

Mesenchymal stem cells are sensitive to bleomycin treatment

Nicolay

Rühle

Perez

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Pulmonary damage occurring in up to 20% of patients is commonly the dose‐limiting toxicity of bleomycin . Preclinical datasets have suggested an attenuation of bleomycin‐induced lung fibrosis by treatment with allogeneic MSCs or activated endogenous MSCs . However, considering the sensitivity and impaired differentiation potential of these stem cells, further analyses are needed investigating the impairment of the MSCs' regenerative abilities by bleomycin treatment.…”

Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning

confidence: 99%

The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity

Rühle

Huber

Saffrich

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

Chemotherapeutic agents are part of the standard treatment algorithms for many malignancies; however, their application and dosage are limited by their toxic effects to normal tissues. Chemotherapy-induced toxicities can be long-lasting and may be incompletely reversible; therefore, causative therapies for chemotherapy-dependent side effects are needed, especially considering the increasing survival rates of treated cancer patients. Mesenchymal stem cells (MSCs) have been shown to exhibit regenerative abilities for various forms of tissue damage. Preclinical data suggest that MSCs may also help to alleviate tissue lesions caused by chemotherapeutic agents, mainly by establishing a protective microenvironment for functional cells. Due to the systemic administration of most anticancer agents, the effects of these drugs on the MSCs themselves are of crucial importance to use stem cell-based approaches for the treatment of chemotherapy-induced tissue toxicities. Here, we present a concise review of the published data regarding the influence of various classes of chemotherapeutic agents on the survival, stem cell characteristics and physiological functions of MSCs. Molecular mechanisms underlying the effects are outlined, and resulting challenges of MSC-based treatments for chemotherapy-induced tissue injuries are discussed.

show abstract

“…G-CSF is a hematopoietic mobilizer and has been applied to all types of leucopenia in the clinical setting. It has been shown that G-CSF can accelerate the regression of fibrosis in organs including heart, lung and liver [4] – [7] . However, whether it has the anti-fibrotic effects in pancreas is still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…During inflammation, BM cells migrate into the diseased organ and further differentiate into myofibroblasts. These BM-derived myofibroblasts has been showed to participate in fibrosis in organs including heart, lung, liver and kidney [4] – [7] . Conversely, there is a growing body of evidence that the BM-derived cells may contribute to the regression of fibrosis [8] .…”

Section: Introductionmentioning

confidence: 99%

Granulocyte Colony-Stimulating Factor Reduces Fibrosis in a Mouse Model of Chronic Pancreatitis

et al. 2014

View full text Add to dashboard Cite

BackgroundChronic pancreatitis (CP) is a necroinflammatory process resulting in extensive pancreatic fibrosis. Granulocyte colony-stimulating factor (G-CSF), a hematopoietic stem cell mobilizer, has been shown to exert an anti-fibrotic effect partly through the enrichment of bone marrow (BM) cells in fibrotic organ. We aimed to test the effect of G-CSF on fibrosis in a mouse model of CP.MethodsCP was induced in C57Bl/6J mice by consecutive cerulein injection (50 µg/kg/day, 2 days a week) for 6 weeks. Mice were then treated with G-CSF (200 µg/kg/day, 5 day a week) or normal saline for 1 week, and sacrificed at week 7 or week 9 after first cerulein injection. Pancreatic histology, pancreatic matrix metallopeptidase 9 (MMP-9), MMP-13 and collagen expression were examined. Pancreatic myofibroblasts were isolated and cultured with G-CSF. Collagen, MMP-9 and MMP-13 expression by myofibroblasts was examined. The BM-mismatched mice model was used to examine the change of BM-derived myofibroblasts and non-myofibroblastic BM cells by G-CSF in the pancreas.ResultsThe pancreatic collagen expression were significantly decreased in the G-CSF-treated group sacrificed at week 9. While collagen produced from myofibroblasts was not affected by G-CSF, the increase of MMP13 expression was observed in vitro. There were no effect of G-CSF in the number of myofibroblasts and BM-derived myofibroblasts. However, the number of non-myofibroblastic BM cells and macrophages were significantly increased in the pancreata of cerulein- and G-CSF-treated mice, suggesting a potential anti-fibrotic role of non-myofibroblastic BM cells and macrophages stimulated by G-CSF.ConclusionsOur data indicated that G-CSF contributed to the regression of pancreatic fibrosis. The anti-fibrotic effects were possibly through the stimulation of MMP-13 from myofibroblasts, and the enhanced accumulation of non-myofibroblastic BM cells and macrophages in the pancreas.

show abstract

Mobilization of Bone Marrow Cells by CSF3 Protects Mice from Bleomycin-Induced Lung Injury

Cited by 15 publications

References 80 publications

Mesenchymal stem cells are sensitive to bleomycin treatment

Mesenchymal stem cells are sensitive to bleomycin treatment

The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity

Granulocyte Colony-Stimulating Factor Reduces Fibrosis in a Mouse Model of Chronic Pancreatitis

Contact Info

Product

Resources

About