RETRACTED: Ischemia postconditioning and mesenchymal stem cells engraftment synergistically attenuate ischemia reperfusion-induced lung injury in rats

Chen, Shu-Chen; Chen, Liangwan; Wu, Xiaonan; Lin, Jiangbo; Fang, Jun; Chen, Xiangqi; Su, Wei; Xu, Jian‐Xin; Gao, Qin; Kang, Mingqiang

doi:10.1016/j.jss.2012.01.039

Cited by 40 publications

(31 citation statements)

References 44 publications

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“…In the present study, Ki67 IHC suggests that most of the resultant human hepatocytes are from cells that proliferate and expand within the diseased recipient liver, rather than direct engraftment of all cells at the time of the initial transplantation. Hepatic engraftment via the portal vein is believed to occur through disruption of the hepatic sinusoidal endothelium and ischemia reperfusion conditioning has been reported to damage LSECs and increase engraftment efficiency . In our kinetic studies, this was indeed observed in the lobes receiving this intervention but overall, fewer than 2% of transplanted cells successfully engraft.…”

Section: Discussionmentioning

confidence: 55%

Long-Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers

et al. 2017

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Liver progenitor cells have the potential to repair and regenerate a diseased liver. The success of any translational efforts, however, hinges on thorough understanding of the fate of these cells after transplant, especially in terms of long-term safety and efficacy. Here, we report transplantation of a liver progenitor population isolated from human fetal livers into immunepermissive mice with follow-up up to 36 weeks after transplant. We found that human progenitor cells engraft and differentiate into functional human hepatocytes in the mouse, producing albumin, alpha-1-antitrypsin, and glycogen. They create tight junctions with mouse hepatocytes, with no evidence of cell fusion. Interestingly, they also differentiate into functional endothelial cell and bile duct cells. Transplantation of progenitor cells abrogated carbon tetrachlorideinduced fibrosis in recipient mice, with downregulation of procollagen and anti-smooth muscle actin. Paradoxically, the degree of engraftment of human hepatocytes correlated negatively with the anti-fibrotic effect. Progenitor cell expansion was most prominent in cirrhotic animals, and correlated with transcript levels of pro-fibrotic genes. Animals that had resolution of fibrosis had quiescent native progenitor cells in their livers. No evidence of neoplasia was observed, even up to 9 months after transplantation. Human fetal liver progenitor cells successfully attenuate liver fibrosis in mice. They are activated in the setting of liver injury, but become quiescent when injury resolves, mimicking the behavior of de novo progenitor cells. Our data suggest that liver progenitor cells transplanted into injured livers maintain a functional role in the repair and regeneration of the liver. STEM CELLS 2018;36:103-113 SIGNIFICANCE STATEMENTLiver stem cells hold tremendous potential as cell therapy for liver injury. However, engraftment efficiency, efficacy, long-term cell fate, and safety issues remain unresolved. Transplantation of human fetal liver stem cells in a mouse liver injury model shows low engraftment efficiency. Under injury stimulus, they can integrate, proliferate, differentiate, and repair the injured liver, returning to a quiescent state as injury abates. They can differentiate into a variety of cell types, including hepatocyte, cholangiocyte, and endothelial-like cells. Metaplasia occurs in an extreme fibrotic milieu and underscores the need to test candidate stem cells for prolonged period in a cirrhotic environment.

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Section: Discussionmentioning

confidence: 55%

Long-Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers

et al. 2017

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“…In addition, stimulation through C3aR and C5aR protect MSCs from oxidative damage (Schraufstatter et al 2009) and MSCs produce a number of antioxidants including hemeoxygenase-1 and superoxide dismutase (Kemp et al 2010;Mougiakakos et al 2011), and have been shown to suppress oxidative stress and inflammation in ischemia reperfusion injury models in vivo (Chen et al 2011Sun et al 2011;Du et al 2012). The exact mechanisms of action are unclear; however, MSC protection in these models was associated with increased expression of IL-10, heme oxygenase-1 (HO-1), and hepatocyte growth factor, decreased expression of the proinflammatory cytokines IL-1b, TNF-a, and interferon g (IFN-g), reduced reactive oxygen species, reduced apoptosis and decreased numbers of activated T cells, and infiltrating immune cells (Hara et al 2011;Sun et al 2011;Chen et al 2012;Du et al 2012).…”

Section: Effect Of Mesenchymal Stromal Cells On Ischemia Reperfusion mentioning

confidence: 99%

Mesenchymal Stromal Cells in Transplantation Rejection and Tolerance

English

Wood

2013

Cold Spring Harbor Perspectives in Medicine

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Mesenchymal stromal cells (MSCs) have recently emerged as promising candidates for cellbased immunotherapy in solid organ transplantation (SOT). In addition to immune modulation, MSCs possess proreparative properties and preclinical studies indicate that MSCs have the capacity to prolong graft survival and in some cases induce tolerance. Currently, the application of MSCs in SOT is being evaluated in phase I/II clinical trials. Whereas the mechanisms of action used by MSC immunomodulation have been somewhat elucidated in vitro, the data from preclinical transplant models have been unclear. Furthermore, the optimal timing, dose, and route of administration remain to be elucidated. Importantly, MSCs have the ability to sense their environment, which may influence their function. In this article, we discuss the impact of the local microenvironment on MSCs and the mechanisms of MSC immunomodulation in the setting of SOT.

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“…A large number of experimental data describe the protective efficacy of these cells in the models of acute kidney injury (AKI) by reducing apoptosis and increasing proliferation of tubular cells [13 && , 14,15]. MSCs were also successfully tested in other organ systems such as liver [17,18], lungs [19] heart [20] and intestines [21]. MSCs were also successfully tested in other organ systems such as liver [17,18], lungs [19] heart [20] and intestines [21].…”

Section: Introductionmentioning

confidence: 99%

Ischemia–reperfusion injury

Souidi

Stolk

Seifert

2013

Current Opinion in Organ Transplantation

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MSCs show promise in protecting against IRI-induced damage. They appear to help recovery mainly by affecting the levels of inflammation and apoptosis during the organ repair process. In addition, they may mediate immunomodulatory effects on the innate and adaptive immune processes triggered during reperfusion and reduce fibrosis. Success in preclinical animal models has led to the initiation of ongoing clinical trials.

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RETRACTED: Ischemia postconditioning and mesenchymal stem cells engraftment synergistically attenuate ischemia reperfusion-induced lung injury in rats

Cited by 40 publications

References 44 publications

Long-Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers

Long-Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers

Mesenchymal Stromal Cells in Transplantation Rejection and Tolerance

Ischemia–reperfusion injury

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