Mesenchymal stem cell–mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice

Yamaza, Takayoshi; Miura, Yasuo; Akiyama, Kentaro; Bi, Yanming; Sonoyama, Wataru; Gronthos, Stan; Chen, Wanjun; Le, Anh D.; Shi, Songtao

doi:10.1182/blood-2008-10-182246

Cited by 43 publications

(50 citation statements)

References 38 publications

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“…In immunocompromised mice that had received subcutaneous bone marrow mesenchymal stem cell transplants, the newly organized ectopic bone/marrow system restored active hematopoiesis via the erythropoietin receptor (EPO-R)/signal transducer and an activator of the transcription 5 (stat5) pathway. Furthermore, the bone marrow mesenchymal stem cells recipient mice exhibited an elevated level of Klotho [24]. Thus, EPO might regulate Klotho expression via EPO-R.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Erythropoietin Mitigates Reductions in Renal Klotho Expression

Sugiura¹,

Yoshida²,

Mitobe³

et al. 2010

Am J Nephrol

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Background: Erythropoietin (EPO) and Klotho expression have both been detected in the kidney. Since a recent study suggested that both EPO and Klotho mitigate kidney damage, we explored the relation between EPO and Klotho in a doxorubicin hydrochloride (DXR)-induced rat nephropathy model treated with recombinant human erythropoietin (rhEPO). Methods: Male Sprague-Dawley rats were subjected to DXR-induced nephropathy. The rhEPO group was intracutaneously injected with rhEPO twice weekly at 4–16 weeks after the DXR injection. The rats were sacrificed at 16 weeks after the DXR administration. Expression of renal Klotho, HSP70, α-smooth-muscle actin and E-cadherin were assessed using real-time PCR or western blotting. The hematocrit, plasma creatinine and phosphate levels were also determined. Immunohistochemical studies and Masson-trichrome staining were performed. Results: The renal Klotho mRNA and Klotho protein expressions were significantly reduced in the DXR nephropathy group. Treatment with rhEPO improved the serum creatinine, phosphate level and histological changes observed in the DXR nephropathy group. The reduction in Klotho expression induced by DXR nephropathy was mitigated by rhEPO administration. Conclusion: rhEPO is involved in the pathophysiology of DXR nephropathy. rhEPO mitigated elevated plasma phosphate concentrations in an experimental model of chronic kidney disease via the expression of Klotho.

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Section: Discussionmentioning

confidence: 99%

Recombinant Human Erythropoietin Mitigates Reductions in Renal Klotho Expression

Sugiura¹,

Yoshida²,

Mitobe³

et al. 2010

Am J Nephrol

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“…The mixtures were subcutaneously transplanted into Begie XIDIII nu/nu mice (female, 8–12 weeks old; Harlan Sprague Dawley Inc., Indianapolis, IN, USA) [31]. A total of 8 weeks after the implantation, the resected tissues were fixed with 4% paraformaldehyde in PBS (pH 7.2) and decalcified with 5% ethylenediaminetetraacetic acid in PBS (pH 7.2) for 2 weeks.…”

Section: Methodsmentioning

confidence: 99%

Stem/Progenitor Cells from Inflamed Human Dental Pulp Retain Tissue Regeneration Potential

et al. 2010

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“…Until recently however, less attention has been devoted to optimizing and determining the therapeutic benefits of the transplantation bone marrow stromal cells. Consequently, the promise of bone marrow mesenchymal stem cells for tissue repair and immune modulation makes identifying the cells a scientific priority (3–5). …”

Section: Introductionmentioning

confidence: 99%

Prospective Identification and Skeletal Localization of Cells Capable of Multilineage Differentiation In Vivo

Taichman

Wang

Shiozawa

et al. 2010

Stem Cells and Development

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A prospective in vivo assay was used to identify cells with potential for multiple lineage differentiation. With this assay it was first determined that the 5-FU resistant cells capable of osseous tissue formation in vivo also migrated towards SDF-1 in vitro. In parallel, an isolation method based upon fluorescence activated cell sorting (FACS) was employed to identify a very small cell embryonic-like (VSEL) Lin−Sca-1+ CD45− cell that with as few as 500 cells were capable of forming bone-like structures in vivo. Differential marrow fractionation studies determined that the majority of the Lin−Sca-1+CD45− cells reside in the subendosteal regions of marrow. To determine if these cells were capable of differentiating into multiple lineages, stromal cells harvested from Col2.3ΔTK mice were implanted with a gelatin sponge into SCID mice to generate thymidine kinase sensitive ossicles. At 1.5 months, 2000 GFP+ Lin−Sca-1+ CD45− cells were injected into the ossicles. At harvest, co-localization of GFP expressing cells with antibodies to the osteoblast specific marker Runx-2 and the adipocyte marker PPARγ were observed. Based upon the ability of the non-cultured cells to differentiate into multiple mesenchymal lineages in vivo and the ability to generate osseous tissues at low density, we propose that this population fulfills many of the characteristics of mesenchymal stem cells.

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Mesenchymal stem cell–mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice

Cited by 43 publications

References 38 publications

Recombinant Human Erythropoietin Mitigates Reductions in Renal Klotho Expression

Recombinant Human Erythropoietin Mitigates Reductions in Renal Klotho Expression

Stem/Progenitor Cells from Inflamed Human Dental Pulp Retain Tissue Regeneration Potential

Prospective Identification and Skeletal Localization of Cells Capable of Multilineage Differentiation In Vivo

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