Liver-specific gene expression in mesenchymal stem cells is induced by liver cells

Lange, Claudia; Bassler, Philipp; Lioznov, Michael; Bruns, Helge; Kluth, Dietrich; Zander, Axel R.; Fiegel, Henning C.

doi:10.3748/wjg.v11.i29.4497

Cited by 92 publications

(73 citation statements)

References 46 publications

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“…14 Hence, it will be adequate to avoid growth factors for clinical applications, as HGF paracrine signaling may contribute to tumorigenesis in vivo 15 ; nonetheless, hepatic differentiation of MSCs without growth factors has not been reported to date. It was found that hepatocyte-specific gene expression in MSCs was induced by coculture with liver cells, 16 suggesting that liver cell coculture system with direct cell-to-cell contact has a stimulatory effect for differentiation of stem cells into hepatocytic lineage and is an optimal environment in vitro for differentiation induction. However, these direct coculture systems may cause difficulty to selectively sort differentiated stem cells for transplantation.…”

mentioning

confidence: 99%

Therapeutic Potential of Bone-Marrow-Derived Mesenchymal Stem Cells Differentiated with Growth-Factor-Free Coculture Method in Liver-Injured Rats

Kim²,

Cho³

et al. 2010

Tissue Engineering Part A

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Mesenchymal stem cell (MSC) differentiation by growth factors may be improper due to possibility of clinical risk. We have previously developed a growth-factor-free coculture method and observed rat MSCs differentiated into hepatic progenitor cells. This study was aimed to validate hepatic differentiation potential in vivo. MSCs from bone marrow of green fluorescent protein-transgenic Sprague-Dawley rats were cocultured with hepatocytes from normal Sprague-Dawley rats, sharing growth-factor-free media. After 14 days, cells were implanted into the spleen of carbon tetrachloride (CCl 4 )-injured rats and kept for 4 weeks. Fibrosis remarkably decreased in CCl 4 / cocultured MSC at weeks 1, 3, and 4. Immunohistochemistry revealed that albumin, a-fetoprotein, and cytokeratin 19 (CK19) expression was high in CCl 4 /cocultured MSC only at week 1. Reverse transcription-polymerase chain reaction and Western blot revealed that CCl 4 /cocultured MSC had reduced a-fetoprotein expression at week 4, whereas CK18 and CK19 exhibited stronger expression. Albumin in CCl 4 /cocultured MSC increased at week 4 only in protein level. We assume that cocultured MSCs had stayed at hepatic progenitor stage until week 3, and differentiated into hepatocytes or bile-ductal epithelial cells afterward. Hepatic progenitor cells from MSC differentiation in the growth-factor-free coculture system may contribute to the therapeutic effect for liver disease in vivo.

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mentioning

confidence: 99%

Therapeutic Potential of Bone-Marrow-Derived Mesenchymal Stem Cells Differentiated with Growth-Factor-Free Coculture Method in Liver-Injured Rats

Kim²,

Cho³

et al. 2010

Tissue Engineering Part A

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“…This suggests that the potential role of CD44 in MSCs migration is represented in CD44 and hyaluronic acid interaction. Some researchers have reported that stem cells can regenerate various cell lineages by trans-differentiation or by a recovery through a mechanism of protection (Lange et al,2005).…”

Section: Discussion:-mentioning

confidence: 99%

Ameliorative Role of Bone Marrow Mesenchymal Stem Cells and Rutin Against Acetaminophen Induced Hepatotoxicity in Adult Male Rats.

Nahrawy¹,

Zahra²,

Dab³

2017

IJAR

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The present study was undertaken to evaluated the therapeutic effect of bone marrow mesenchymal stem cells (MSCs) and/or rutin against acetaminophen induced hepatotoxicity in adult male albino-rats. Rats were divided into 5 groups: Group 1 (-ve control group) with no treatment; Group 2 (Acetaminophen recovery group)rats were given orally acetaminophen 750 mg/kg b.wt every 72h for two weeks then left for 60 days without any treatment ; Group 3 (Acet +rutin group) rats were given orally acetaminophen 750 mg/kg b.wt every 72h for two weeks then treated orally with rutin 25 mg/kg b.wt daily for 8 weeks ; Group 4 (Acet + MSCs) acetaminophen group then injected intravenously with a single dose of MSCs (1X10 6 ) cell / cm2 saline /animale ) and Group 5 (Acet +rutin and MSCs treated group) rats were given (750 ) mg/kg b.wt Acettaminophen every 72h for two weeks then injected intravenously with a single dose of MSCs (1X10 6 ) cell / cm2 saline /animale ) and rutin.

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“…2,3 In particular, MSCs can differentiate into hepatocyte-like cells through a specific cell-signaling pathway upon stimulation with a combination of hepatocyte growth factor (HGF), fibroblast growth factor, epidermal growth factor and other cytokines. [4][5][6] However, in a culture of human bone marrowderived MSCs (BM-MSCs) and hepatocytes, BM-MSCs that undergo hepatic differentiation probably account for only a small percentage of the population, 7 and any differentiation may not significantly change the outcome of the bone marrow stromal cell (BMSC) and hepatocyte coculture experiments. 8 MSCs have recently emerged as promising candidates for cell-based immunotherapy because these cells can modulate the immune responses in various ways.…”

Section: Therapeutic Mechanism Of Msc Transplantationmentioning

confidence: 99%

Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases

Zhang

et al. 2010

Cell Mol Immunol

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Transplantation of mesenchymal stem cells (MSCs) has been recently studied in animal models, and in clinical trials of patients with fulminant hepatic failure, end-stage liver diseases and inherited metabolic disorders. Modulatory cytokines produced by MSCs can inhibit immunocyte proliferation and migration to the liver, thereby attenuating inflammatory injury and reducing hepatocyte apoptosis. In addition, MSCs play an important role in regressing liver fibrosis and in supporting the function, proliferation and differentiation of endogenous hepatocytes under appropriate conditions. Although remarkable progress has been achieved in basic and clinical MSC studies, optimal therapeutic regimens for the clinical application of MSCs, such as optimal doses, transplantation routine and interval period for transplantation, need to be elucidated in detail. Furthermore, the long-term safety and therapeutic efficacy of MSC transplantation should be evaluated in future clinical trials. This review summarizes our current understanding of the immunomodulatory effects of MSC therapies on human liver diseases.

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Liver-specific gene expression in mesenchymal stem cells is induced by liver cells

Abstract: The results indicate that (1) rat MSC from bone marrow can differentiate towards hepatocytic lineage in vitro, and (2) that the microenvironment plays a decisive role for the induction of hepatic differentiation of rMSC.

Cited by 92 publications

References 46 publications

Therapeutic Potential of Bone-Marrow-Derived Mesenchymal Stem Cells Differentiated with Growth-Factor-Free Coculture Method in Liver-Injured Rats

Therapeutic Potential of Bone-Marrow-Derived Mesenchymal Stem Cells Differentiated with Growth-Factor-Free Coculture Method in Liver-Injured Rats

Ameliorative Role of Bone Marrow Mesenchymal Stem Cells and Rutin Against Acetaminophen Induced Hepatotoxicity in Adult Male Rats.

Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases

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