Improvement of ventilator-induced lung injury by IPS cell-derived conditioned medium via inhibition of PI3K/Akt pathway and IP-10-dependent paracrine regulation

Li, Lifu; Liu, Yung-Yang; Yang, Cheng‐Ta; Chien, Yueh; Twu, Nae‐Fang; Wang, Mong‐Lien; Wang, Chien‐Ying; Huang, Chung-Chi; Kao, Kuo‐Chin; Hsu, Han‐Shui; Wu, Cheng‐Wen; Chiou, Shih‐Hwa

doi:10.1016/j.biomaterials.2012.09.042

Cited by 40 publications

(36 citation statements)

References 40 publications

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“…Various studies showed that conditioned medium have been tested in various kinds of diseases/conditions (Table 1) [1, 3–33], that is, alopecia [3, 5], acute and chronic hind limb ischemia [6–9], acute and chronic wound healing [4, 10–14], myocardial infarct [1, 15–18], acute liver injury/failure [19–22], cerebral injury/ischemia/stroke [23–27], spinal cord injury [28], lung injury [32], and bone defect [33], and showed improvement of the conditions. Moreover, chronic kidney disease that was treated using human embryonic stem cell-derived mesenchymal stem cell (huESC-MSC) CM showed decreased systolic blood pressure and proteinuria and improvement in tubular and glomerular damage, renal blood flow, and glomerular filtration rate [29].…”

Section: Resultsmentioning

confidence: 99%

Prospect of Stem Cell Conditioned Medium in Regenerative Medicine

Pawitan

2014

BioMed Research International

358

320

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Background. Stem cell-derived conditioned medium has a promising prospect to be produced as pharmaceuticals for regenerative medicine. Objective. To investigate various methods to obtain stem cell-derived conditioned medium (CM) to get an insight into their prospect of application in various diseases. Methods. Systematic review using keywords “stem cell” and “conditioned medium” or “secretome” and “therapy.” Data concerning treated conditions/diseases, type of cell that was cultured, medium and supplements to culture the cells, culture condition, CM processing, growth factors and other secretions that were analyzed, method of application, and outcome were noted, grouped, tabulated, and analyzed. Results. Most of CM using studies showed good results. However, the various CM, even when they were derived from the same kind of cells, were produced by different condition, that is, from different passage, culture medium, and culture condition. The growth factor yields of the various types of cells were available in some studies, and the cell number that was needed to produce CM for one application could be computed. Conclusion. Various stem cell-derived conditioned media were tested on various diseases and mostly showed good results. However, standardized methods of production and validations of their use need to be conducted.

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Section: Resultsmentioning

confidence: 99%

Prospect of Stem Cell Conditioned Medium in Regenerative Medicine

Pawitan

2014

BioMed Research International

358

320

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“…Further evidence showed that the direct administration of iPSC-conditioned medium alone ameliorated acute lung injury induced by endotoxin and ventilator effectively. 4,5 Intriguingly, our recent study further revealed that treatment with iPSC-conditioned medium increased the recipient survival effectively in rat ischemia/reperfusion-induced acute kidney injury models. 6 These findings highlighted that iPSC-conditioned medium represents a favorable source of stem cell-based therapy that carries minimal risk for teratoma formation in stem cell-based therapy.…”

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confidence: 92%

Induced Pluripotent Stem Cell–conditioned Medium Suppressed Melanoma Tumorigenicity Through the Enhancement of Natural-Killer Cellular Immunity

Hsieh

Luo

Chien

et al. 2016

Journal of Immunotherapy

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Induced pluripotent stem cells (iPSCs) can secrete cytokines that are involved in T-cell development and affect cytotoxic activity. To assess the effect of iPSC-conditioned medium on tumorigenicity, we retrieved splenocytes from B6 mice and cocultured them with or without irradiated B16 melanoma cells, mouse interleukin-2 (mIL-2), or iPSC-conditioned medium. Splenocyte cytotoxicity assays against B16 melanoma cells [as cytotoxic T lymphocyte (CTL) activity] and P815 cells [as natural killer (NK) activity] were performed. IL-10 and interferon-γ concentrations were measured. An in vivo subcutaneous B16 melanoma growth model was performed in B6 mice and treated with iPSC-conditioned medium. The lymphocyte subpopulation depletion test was performed to determine effectors against B16 melanoma cells. We found that unstimulated splenocytes had little cytotoxic activity. Without tumor cells, mIL-2 could augment iPSC-conditioned medium-treated CTL and NK activities (P<0.01). With irradiated tumor cells, mIL-2 treatment of splenocytes could not enhance CTL or NK activity, but iPSC-conditioned medium could enhance CTL and NK activity (P<0.001). Irradiated tumor cells induced mice splenocytes to secrete more IL-10, similar to mIL-2 treatment, but not iPSC-conditioned medium treatment. mIL-2 had better efficacy than conditioned medium in inducing splenocyte interferon-γ production. The CTL and NK cell depletion test showed that the immunostimulating effect of iPSC-conditioned medium on splenocytes was through the enhancement of NK cellular activity (P<0.05). The subcutaneous melanoma growth model showed that B16-bearing mice treated with an iPSC-conditioned medium intraperitoneal injection had a decreased tumor growth rate (P<0.01). Our study suggests that iPSC-conditioned medium had a protective effect against tumor-induced immunosuppression through the enhancement of host NK cellular activity.

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“…Further, other evidence has indicated that the therapeutic effects of stem cell transplantation may be attributed to paracrine effects, but not to tissue regeneration through stem cell differentiation. 36,37 The oncogene c-Myc has been shown to substantially contribute to tumor formation. 38,39 Dysregulated expression of c-Myc occurs in a wide range of human cancers and is often associated with poor prognosis, indicating a key role for this oncogene in tumor progression.…”

Section: Figmentioning

confidence: 99%

Induced Pluripotent Stem Cells Without c-Myc Ameliorate Retinal Oxidative Damage via Paracrine Effects and Reduced Oxidative Stress in Rats

Fang

Yang

Chiou³

et al. 2014

Journal of Ocular Pharmacology and Therapeutics

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Purpose: To investigate the efficacy and mechanisms of non-c-Myc induced pluripotent stem cell (iPSC) transplantation in a rat model of retinal oxidative damage. Methods: Paraquat was intravitreously injected into Sprague-Dawley rats. After non-c-Myc iPSC transplantation, retinal function was evaluated by electroretinograms (ERGs). The generation of reactive oxygen species (ROS) was determined by lucigenin-and luminol-enhanced chemiluminescence. The expression of brainderived neurotrophic factor, ciliary neurotrophic factor, basic fibroblast growth factor (bFGF), stromal cellderived factor (SDF)-1a, and CXCR4 was measured by immunohistochemistry and ELISA. An in vitro study using SH-SY5Y cells was performed to verify the protective effects of SDF-1a.Results: Transplantation of non-c-Myc iPSCs effectively promoted the recovery of the b-wave ratio in ERGs and significantly ameliorated retinal damage. Non-c-Myc iPSC transplantation decreased ROS production and increased the activities of superoxide dismutase and catalase, thereby reducing retinal oxidative damage and apoptotic cells. Moreover, non-c-Myc iPSC transplantation resulted in significant upregulation of SDF-1a, followed by bFGF, accompanied by a significant improvement in the ERG. In vitro studies confirmed that treatment with SDF-1a significantly reduced apoptosis in a dose-dependent manner in SH-SY5Y cells. Most transplanted cells remained in the subretinal space, with spare cells expressing neurofilament M markers at day 28. Six months after transplantation, no tumor formation was seen in animals with non-c-Myc iPSC grafts. Conclusions: We demonstrated the potential benefits of non-c-Myc iPSC transplantation for treating oxidativedamage-induced retinal diseases. SDF-1a and bFGF play important roles in facilitating the amelioration of retinal oxidative damage after non-c-Myc iPSC transplantation.

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Improvement of ventilator-induced lung injury by IPS cell-derived conditioned medium via inhibition of PI3K/Akt pathway and IP-10-dependent paracrine regulation

Cited by 40 publications

References 40 publications

Prospect of Stem Cell Conditioned Medium in Regenerative Medicine

Prospect of Stem Cell Conditioned Medium in Regenerative Medicine

Induced Pluripotent Stem Cell–conditioned Medium Suppressed Melanoma Tumorigenicity Through the Enhancement of Natural-Killer Cellular Immunity

Induced Pluripotent Stem Cells Without c-Myc Ameliorate Retinal Oxidative Damage via Paracrine Effects and Reduced Oxidative Stress in Rats

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