Investigation of bone marrow mesenchymal stem cells (BM MSCs) involvement in idiopathic pulmonary fibrosis (IPF)

Αντωνίου, Κατερίνα; Papadaki, Helen Α.; Soufla, Giannoula; Kastrinaki, Maria-Christina; Damianaki, Athina; Koutala, Helen; Spandidos, Demetrios Α.; Siafakas, Nikolaos M.

doi:10.1016/j.rmed.2010.04.015

Cited by 37 publications

(30 citation statements)

References 50 publications

(43 reference statements)

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“…It is generally agreed that the mechanism of RILI includes radiation-induced injury of parenchymal cells [44], delayed activation of inflammatory reaction [45], and radiation-induced epithelial-mesenchymal transition (EMT) which is reported to mediate pulmonary fibrosis [46]. Therefore, the mechanism of MSC therapy for RILI is considered to regulate the inflammatory response [47-49] and the differentiation of damaged parenchymal cells to promote reconstruction [50]. Recently, some studies revealed the anti-apoptotic function of MSCs.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability

Zhu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage. However, unlike other injuries, RILI received limited therapeutic effects from implanted MSCs due to local hypoxia and extensive reactive oxygen species (ROS) in irradiated lungs. Since the poor survival of MSCs is primarily due to hypoxia and ROS generation, we hypothesize that persistent and adaptive hypoxia treatment induces enhanced resistance to hypoxic stress in implanted MSC. The aim of this study is to investigate whether persistent and adaptive hypoxia treatment of bmMSCs prior to their transplantation in injured mice enhanced survival and improved curative effects in RILI. Methods: Primary bmMSCs were obtained from the marrow of six-week-old male C57BL6/J mice and were cultured either under normoxic conditions (21% O₂) or hypoxic conditions (2.5% O₂). Mice were injected with normoxia/hypoxia MSCs after thoracic irradiation (20 Gy). The therapeutic effects of MSCs on RILI were assessed by pathological examinations that included H&E staining, Masson staining and α-SMA staining; meanwhile, inflammatory factors were measured using an ELISA. The morphology of MSCs in vitro was recorded using a microscope and identified by flow cytometry, cell viability was measured using the CCK-8 assay, the potential for proliferation was detected by the EdU assay, and ROS levels were measured using a ROS fluorogenic probe. In addition, HIF-1α and several survival pathway proteins (Akt, p-Akt, Caspase-3) were also detected by western blotting. Results: Implanted MSCs alleviated both early radiation-induced pneumonia and late pulmonary fibrosis. However, hypoxia MSCs displayed a more pronounced therapeutic effect compared to normoxia MSCs. Compared to normoxia MSCs, the hypoxia MSCs demonstrated greater cell viability, an enhanced proliferation potential, decreased ROS levels and increased resistance to hypoxia and ROS stress. In addition, hypoxia MSCs achieved higher activation levels of HIF-1α and Akt, and HIF-1α played a critical role in the development of resistance. Conclusion: Hypoxia enhances the therapeutic effect of mesenchymal stromal cells on radiation-induced lung injury by promoting MSC proliferation and improving their antioxidant ability, mediated by HIF-1α.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability

Zhu

et al. 2017

Cell Physiol Biochem

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“…Recent studies have shown that bone marrow-derived circulating progenitor cells could accumulate in the lung and contribute to pulmonary fibrosis after lung injury (2). In experimental pulmonary fibrosis in mice, bone marrow progenitor recruitment accounts for ϳ20% of the fibroblast pool (36).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Wnt/β-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury

Wang

Zhu

Sun

et al. 2014

American Journal of Physiology-Cell Physiology

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“…Thus, since vessels express CD34 marker, we cannot assert that CD34 is lost during vessel formation with progenitor cells such as previously described with fibrocytes [55], largely involved in IPF. However, one of the limitation of using CD34 is its widely expression on various other cells such as fibrocytes [55] but also mesenchymal [56], epithelial, and even cancer stem cells [30]. Thus, the use of CD34 as an EPC marker is questionable and the addition of specific markers would be useful to discriminate these different cellular lineages from the putative EPC.…”

Section: Discussionmentioning

confidence: 99%

Imbalance of circulating endothelial cells and progenitors in idiopathic pulmonary fibrosis

et al. 2012

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Investigation of bone marrow mesenchymal stem cells (BM MSCs) involvement in idiopathic pulmonary fibrosis (IPF)

Abstract: The increased CXCR4 expression by patient MSCs suggests that the BM is probably implicated in the pathophysiology of IPF by mobilizing MSCs in response to or preceding lung injury. The potential role of BM MSCs in IPF is another interesting field for further investigation.

Cited by 37 publications

References 50 publications

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability

Inhibition of Wnt/β-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury

Imbalance of circulating endothelial cells and progenitors in idiopathic pulmonary fibrosis

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