Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Hepatic Ischemia Reperfusion Injury in a Rat Model

Kanazawa, Hideko; Fujimoto, Yasuhiro; Teratani, Takumi; Iwasaki, Junji; Kasahara, Naoya; Negishi, Kouji; Tsuruyama, Tatsuaki; Üemoto, Shinji; Kobayashi, Eiji

doi:10.1371/journal.pone.0019195

Cited by 161 publications

(143 citation statements)

References 25 publications

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“…These findings indicated that the characteristic immunophenotype of rat bone marrow-derived MSCs was exhibited in the isolated cells. [25][26][27] MSCs have the ability to differentiate into osteogenic and adipogenic lineages. 25,26 The cells described herein are able to differentiate into osteocytes and adipocytes (Fig.…”

Section: Characteristics Of Mscs Isolated From Rat Bone Marrowmentioning

confidence: 99%

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells

Hirabaru

Kuroki

Adachi

et al. 2015

Tissue Engineering Part C: Methods

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Mesenchymal stem cells (MSCs) are known to have a protective effect on islet cells. Cell sheets developed using tissue engineering help maintain the function of the cells themselves. This study describes a tissue engineering approach using islets with MSC sheets to improve the therapeutic effect of islet transplantation. MSCs were obtained from Fischer 344 rats and engineered into cell sheets using temperature-responsive culture dishes. The islets obtained from Fischer 344 rats were seeded onto MSC sheets, and the islets with MSC sheets were harvested by low-temperature treatment after coculture. The functional activity of the islets with MSC sheets was confirmed by a histological examination, insulin secretion assay, and quantification of the levels of cytokines. The therapeutic effects of the islets with MSC sheets were investigated by transplanting the sheets at subcutaneous sites in severe combined immunodeficiency (SCID) mice with streptozotocin-induced diabetes. Improvement of islet function and viability was shown in situ on the MSC sheet, and the histological examination showed that the MSC sheet maintained adhesion factor on the surface. In the recipient mice, normoglycemia was maintained for at least 84 days after transplantation, and neovascularization was observed. These results demonstrated that islet transplantation in a subcutaneous site would be possible by using the MSC sheet as a scaffold for islets.

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Section: Characteristics Of Mscs Isolated From Rat Bone Marrowmentioning

confidence: 99%

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells

Hirabaru

Kuroki

Adachi

et al. 2015

Tissue Engineering Part C: Methods

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“…The Luc/LacZ-dual-Tg rat was established by mating the Luc-rat and the LacZ-rat [15,16]. Rat MSCs were established and maintained as described elsewhere [17]. Bone marrow mononuclear cells from a healthy volunteer were purchased from LONZA Walkersville Inc., http://www.…”

Section: Culture and Manipulation Of Human And Rat Mscs And Human Endmentioning

confidence: 99%

Xenotransplanted Embryonic Kidney Provides a Niche for Endogenous Mesenchymal Stem Cell Differentiation into Erythropoietin-Producing Tissue

et al. 2012

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Recent findings have demonstrated that stem cells can differentiate into mature tissue when supplied with a niche containing factors identical to those in the normal developmental program. A niche for the development of an organ can be provided by xenotransplantation of a similar developing organ. However, this process has many technical, safety, and ethical concerns. Here, we established xenotransplantation models that control endogenous mesenchymal stem cell (MSC) differentiation into mature erythropoietin (EPO)-producing tissue in a niche provided by a developing xenometanephros. Transplantation of rat metanephroi into mouse omentum, and similarly pig metanephroi into cat omentum, led to the recruitment of host cells and EPO production. EPO-expressing cells were not differentiated from integrating vessels because they did not coexpress endothelial markers (Tie-2 and VE-cadherin). Instead, EPOexpressing cells were shown to be derived from circulating host cells, as shown by enhanced green fluorescent protein (EGFP) expression in the grown transplants of chimeric mice bearing bone marrow from a transgenic mouse expressing EGFP under the control of the EPO promoter. These results suggest that donor cell recruitment and differentiation in a xenotransplanted developing organ may be consistent between species. The cells responsible for EPO expression were identified as MSCs by injecting human bone marrow-derived MSCs and endothelial progenitor cells into NOD/SCID mice. Furthermore, using metanephroi from transgenic ER-E2F1 suicide-inducible mice, the xenotissue component could be eliminated, leaving autologous EPO-producing tissue. Our findings may alleviate adverse effects due to long-lasting immunosuppression and help mitigate ethical concerns.

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“…The multipotent differentiation ability of mesenchymal stem cells (MSCs) has been reported and it has attracted a lot of attention as a reliable cell source for liver therapy [9][10][11].…”

mentioning

confidence: 99%

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis

Yan

Wang

et al. 2013

Stem Cells and Development

715

557

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Mesenchymal stem cells (MSCs) have been considered as an attractive tool for the therapy of diseases. Exosomes excreted from MSCs can reduce myocardial ischemia/reperfusion damage and protect against acute tubular injury. However, whether MSC-derived exosomes can relieve liver fibrosis and its mechanism remain unknown. Previous work showed that human umbilical cord-MSCs (hucMSCs) transplanted into acutely injured and fibrotic livers could restore liver function and improve liver fibrosis. In this study, it was found that transplantation of exosomes derived from hucMSC (hucMSC-Ex) reduced the surface fibrous capsules and got their textures soft, alleviated hepatic inflammation and collagen deposition in carbon tetrachloride (CCl 4 )-induced fibrotic liver. hucMSC-Ex also significantly recovered serum aspartate aminotransferase (AST) activity, decreased collagen type I and III, transforming growth factor (TGF)-b1 and phosphorylation Smad2 expression in vivo. In further experiments, we found that epithelial-to-mesenchymal transition (EMT)-associated markers E-cadherin-positive cells increased and N-cadherin-and vimentin-positive cells decreased after hucMSC-Ex transplantation. Furthermore, the human liver cell line HL7702 underwent typical EMT after induction with recombinant human TGF-b1, and then hucMSC-Ex treatment reversed spindle-shaped and EMT-associated markers expression in vitro. Taken together, these results suggest that hucMSC-Ex could ameliorate CCl 4 -induced liver fibrosis by inhibiting EMT and protecting hepatocytes. This provides a novel approach for the treatment of fibrotic liver disease.

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Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Hepatic Ischemia Reperfusion Injury in a Rat Model

Cited by 161 publications

References 25 publications

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells

Xenotransplanted Embryonic Kidney Provides a Niche for Endogenous Mesenchymal Stem Cell Differentiation into Erythropoietin-Producing Tissue

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis

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