Early activated hepatic stellate cell-derived paracrine molecules modulate acute liver injury and regeneration

Chang, Wenju; Song, Lujun; Chang, Xiujuan; Ji, Meiling; Wang, Hongshan; Qin, Xinyu; Niu, Weidong

doi:10.1038/labinvest.2016.130

Cited by 29 publications

(24 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PI3K/AKT is a classical signaling pathway that plays a key role in a veriety of physiological and pathological processes such as cell survival, growth, mogility, and apoptosis [49] and is known to inhibit in ammation and apoptosis by regulating multiple target proteins such as NF-κB and Bcl-2 family [50]. Previous studies have shown that IGF-1R/PI3K/AKT signaling pathway affect early liver regeneration and is involved in the development of APAP-induced ALF [51,52]. ERK is one of MAPK pathways and participates in the oxidative stress, cell apoptosis, and in ammation [53].…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Acetaminophen-induced Acute Liver Failure Through Activating ERK and IGF-1R/PI3K/AKT Signaling Pathways

Wu¹,

Zhang²,

Cao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Human umbilical cord mesenchymal stem cells (hUCMSCs) transplantation has been proposed as a promising therapeutic approach for treating acute liver failure (ALF), but its application is limited by immune rejection and tumor formation. Exosomes contain various bioactive cargos including mRNA, microRNA, and protein that can alter the cellular enviroment to enhance tissue repair. However, the exact effects of hUCMSCs derived exosomes (hUCMSC-Exo) on the healing of ALF and their potential mechanisms are not explored.Methods: In vivo, mouse model of ALF were set up through a single intraperitoneal injection of acetaminophen (APAP, 380 mg/kg). In vitro, human hepatocyte cells LO2 were treated with APAP (5 mM). Then APAP-induced ALF mice and APAP-injured LO2 cells were treated with hUCMSC-Exo. Finally, the effects and the mechanisms were estimated.Results: We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Conclusions: Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways, suggesting that administration of hucMSC-Exo may be an alternative approach for the treatment of ALF.

show abstract

Section: Discussionmentioning

confidence: 99%

Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Acetaminophen-induced Acute Liver Failure Through Activating ERK and IGF-1R/PI3K/AKT Signaling Pathways

Wu¹,

Zhang²,

Cao

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The injection of CM without stem cells has been studied in various contexts but not in terms of vocal fold regeneration. As far as we know, this study is the first report on the injection of CM alone in the treatment of injured vocal folds in an animal model.…”

Section: Discussionmentioning

confidence: 99%

The Ability of Conditioned Media From Stem Cells to Repair Vocal Fold Injuries

et al. 2019

View full text Add to dashboard Cite

Objective This study investigated the ability of hypoxia‐induced 25‐fold concentrated conditioned media (hCM) from human nasal inferior turbinate‐derived mesenchymal stem cells (hTMSC) to repair injured vocal folds during the early phase of the wound‐healing process. Methods The vocal fold was injured in Sprague‐Dawley rats. Next, hCM from hTMSC (the hCM group) or hTMSC (the hTMSC group) were injected into the injured vocal folds. As a control, saline (the phosphate‐buffered saline group) or 25‐fold concentrated media (the media group) was injected in the same manner. The vocal folds were harvested for quantitative real‐time polymerase chain reaction (PCR) at 1 week and 2 weeks after injury. Histologic evaluation was performed at 3 weeks postinjury. Results In the hCM group at 1 week after injury, PCR showed that the genes encoding hyaluronan synthase (HAS), HAS 1, and HAS 2 were significantly upregulated compared to the media and normal groups. The gene encoding procollagen III was significantly downregulated compared to the media group. Nearly identical results were obtained for the hTMSC group at 1 week after injury. Histological examination showed that the hCM group was similar to or better than the hTMSC group in collagen deposition and hyaluronic acid production. Conclusion The injection of hCM into injured vocal folds produced antifibrotic effects in the early phase of wound healing. These effects were equivalent to those produced by the injection of hTMSC. These results provide a foundation for the future clinical use of hCM for vocal fold regeneration. Level of Evidence NA Laryngoscope, 129:1867–1875, 2019

show abstract

“…The paracrine effects of stem cells have been studied in various contexts. [36][37][38][39] However, the paracrine effects of stem cells in terms of conditioned medium have not been studied in the sphere of vocal fold regeneration. Further study is needed.…”

Section: Discussionmentioning

confidence: 99%

The Ability of Human Nasal Inferior Turbinate–Derived Mesenchymal Stem Cells to Repair Vocal Fold Injuries

Kim

Choi

Park

et al. 2018

Otolaryngol.--head neck surg.

View full text Add to dashboard Cite

Objective This study investigated the ability of implanted human nasal inferior turbinate-derived mesenchymal stem cells (hTMSCs) to repair injured vocal folds. To this end, we used quantitative real-time polymerase chain reaction (PCR) to analyze the early phase of wound healing and histopathological analysis to explore the late phase of wound healing in xenograft animal models. Study Design Prospective animal study. Setting Research laboratory. Subjects and Methods The right-side lamina propria of the vocal fold was injured in 20 rabbits and 30 rats. Next, hTMSCs were implanted into half of the injured vocal folds (hTMSC groups). As a control, phosphate-buffered saline (PBS) was injected into the other half of the injured vocal folds (PBS groups). Rat vocal folds were harvested for polymerase chain reaction (PCR) at 1 week after injury. Rabbit vocal folds were evaluated endoscopically and the larynges harvested for histological and immunohistochemical examination at 2 and 8 weeks after injury. Results In the hTMSC group, PCR showed that hyaluronan synthase ( HAS) 1, HAS 2, and transforming growth factor ( TGF)-β1 were significantly upregulated compared with the PBS group. Procollagen type III ( COL III) messenger RNA expression was significantly upregulated in the PBS group compared with the normal group. Histological analyses showed that hTMSC administration afforded more favorable collagen and hyaluronic acid deposition than was evident in the controls. Implanted hTMSCs were observed in injured vocal folds 2 weeks after implantation. Conclusions Our results show that hTMSCs implantation into injured vocal folds facilitated vocal fold regeneration, with presenting antifibrotic effects.

show abstract

Early activated hepatic stellate cell-derived paracrine molecules modulate acute liver injury and regeneration

Cited by 29 publications

References 26 publications

Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Acetaminophen-induced Acute Liver Failure Through Activating ERK and IGF-1R/PI3K/AKT Signaling Pathways

Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Acetaminophen-induced Acute Liver Failure Through Activating ERK and IGF-1R/PI3K/AKT Signaling Pathways

The Ability of Conditioned Media From Stem Cells to Repair Vocal Fold Injuries

The Ability of Human Nasal Inferior Turbinate–Derived Mesenchymal Stem Cells to Repair Vocal Fold Injuries

Contact Info

Product

Resources

About