Pre‐treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases

Hu, Chenxia; Wang, Zhongwen; Li, Lanjuan

doi:10.1111/jcmm.14788

Cited by 63 publications

(53 citation statements)

References 76 publications

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“…More and more studies have shown that MSC therapy could promote cutaneous wound healing and reorganized the structure of skin 4,5 . Meanwhile, pre‐treatment of MSCs could enhance the function and efficacy of therapy, and many studies focus on how to optimize MSCs before their applications 6‐8 . However, many studies have shown that only part of transplanted MSCs can eventually survive and incorporate into the host tissues 9‐13 .…”

Section: Introductionmentioning

confidence: 99%

Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis

et al. 2020

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Objectives Skin serves as the major interface between the external environment and body which is liable to many kinds of injuries. Mesenchymal stem cell (MSC) therapy has been widely used and became a promising strategy. Pre‐treatment with chemical agents, hypoxia or gene modifications can partially protect MSCs against injury, and the pre‐treated MSCs show the improved differentiation, homing capacity, survival and paracrine effects regard to attenuating injury. The aim of this study was to investigate whether the exosomes from the educated MSCs contribute to accelerate wound healing process. Materials and methods We extracted the exosomes from the two educated MSCs and utilized them in the cutaneous wound healing model. The pro‐angiogenetic effect of exosomes on endothelial cells was also investigated. Results We firstly found that MSCs pre‐treated by exosomes from neonatal serum significantly improved their biological functions and the effect of therapy. Moreover, we extracted the exosomes from the educated MSCs and utilized them to treat the cutaneous wound model directly. We found that the released exosomes from MSCs which educated by neonatal serum before had the more outstanding performance in therapeutic effect. Mechanistically, we revealed that the recipient endothelial cells (ECs) were targeted and the exosomes promoted their functions to enhance angiogenesis via regulating AKT/eNOS pathway. Conclusions Our findings unravelled the positive effect of the upgraded exosomes from the educated MSCs as a promising cell‐free therapeutic strategy for cutaneous wound healing.

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Section: Introductionmentioning

confidence: 99%

Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis

et al. 2020

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“…The migration ability and efficacy of MSCs can be significantly improved by various pretreatment protocols before application in vivo [9,10]. As confirmed by Wang et al, gene-modified c-Met overexpression significantly improved the homing ability to the damaged liver and the anti-ALF efficacy of MSCs [11].…”

Section: Introductionmentioning

confidence: 85%

“…As shown in the characterization experiments of cultured cells, the expression rates of CD90 and CD105 were greater than 95%, while those of CD45 and CD34 were less than 2%, and the good multidifferentiation potential was also verified. The efficacy of MSCs on ALF could be significantly improved by effective modification or pretreatment [10,21]. Although MSCs can differentiate into hepatocytes, recent studies have shown that microenvironment created by MSCs is the critical factor for their efficacy in improving the pathophysiological process of liver diseases [8].…”

Section: Discussionmentioning

confidence: 99%

“…The efficacy of MSCs on ALF could be significantly improved by effective modification or pretreatment [ 10 , 21 ]. Although MSCs can differentiate into hepatocytes, recent studies have shown that microenvironment created by MSCs is the critical factor for their efficacy in improving the pathophysiological process of liver diseases [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

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IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression

Nie

Mei

et al. 2020

Stem Cells International

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Background. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1β pretreatment on the efficacy and homing ability of MSCs in ALF. Methods. MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1β-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. Results. MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1β pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1β pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. Conclusion. IL-1β pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF.

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“…Diverse human mesenchymal stem/stromal cell (MSC)-derived hepatocyte-like cells (HLCs) have been investigated as alternatives to hPHeps [8,9]. Human deciduous pulp stem cells were first identified in the dental pulp tissues of exfoliated deciduous teeth, namely stem cells from human exfoliated deciduous teeth (SHED) [10], and are beneficial for the treatment of autoimmune, liver, and spinal injury diseases [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells

et al. 2021

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Background Stem cells from human exfoliated deciduous teeth (SHED) have been reported to show the in vivo and in vitro hepatic differentiation, SHED-Heps; however, the cholangiogenic potency of SHED-Heps remains unclear. Here, we hypothesized that SHED-Heps contribute to the regeneration of intrahepatic bile duct system in chronic fibrotic liver. Methods SHED were induced into SHED-Heps under cytokine stimulation. SHED-Heps were intrasplenically transplanted into chronically CCl4-treated liver fibrosis model mice, followed by the analysis of donor integration and hepatobiliary metabolism in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile duct system in the recipient liver. Furthermore, SHED-Heps were induced under the stimulation of tumor necrosis factor alpha (TNFA). Results The intrasplenic transplantation of SHED-Heps into CCl4-treated mice showed that donor SHED-Heps behaved as human hepatocyte paraffin 1- and human albumin-expressing hepatocyte-like cells in situ and ameliorated CCl4-induced liver fibrosis. Of interest, the integrated SHED-Heps not only expressed biliary canaliculi ATP-binding cassette transporters including ABCB1, ABCB11, and ABCC2, but also recruited human keratin 19- (KRT19-) and KRT17-positive cells, which are considered donor-derived cholangiocytes, regenerating the intrahepatic bile duct system in the recipient liver. Furthermore, the stimulation of TNFA induced SHED-Heps into KRT7- and SRY-box 9-positive cells. Conclusions Collectively, our findings demonstrate that infused SHED-Heps showed cholangiogenic ability under the stimulation of TNFA in CCl4-damaged livers, resulting in the regeneration of biliary canaliculi and interlobular bile ducts in chronic fibrotic liver. Thus, the present findings suggest that SHED-Heps may be a novel source for the treatment of cholangiopathy.

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Pre‐treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases

Cited by 63 publications

References 76 publications

Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis

Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis

IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression

Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells

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