Skip to main content

Advertisement

SpringerLink
Log in

Comparison of multipotency and molecular profile of MSCs between CKD and healthy rats

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

We previously showed that mesenchymal stem cells (MSCs) can differentiate into a functional miniature kidney, suggesting that MSCs may be a cell source for kidney regeneration. However, MSCs from long-term dialysis patients, which have been exposed to uremic toxin, can exhibit reduced viability. Therefore, the aim of this study was to examine the gene expression profiles and differentiation capabilities of bone marrow- and adipose-derived MSCs from chronic kidney disease (CKD) model rats. CKD was induced in rats by adenine feeding, and then MSCs were isolated from bone marrow (BMSCs) and adipose tissue (ASCs). After confirming MSC surface marker expression, comprehensive gene expression profiles were obtained by RT-PCR array. MSCs were differentiated into adipocytes, osteoblasts, and chondrocytes, and histological and/or functional assays were performed. Tgfb3 expression was up-regulated, while Bmp6, Gdf15, Mmp2, and Vegfa were down-regulated in CKD-ASCs compared with Control-ASCs. There were no significant differences in the gene expression of stemness markers, and the morphology of cells that underwent adipogenesis, osteogenesis, and chondrogenesis, or GPDH activity between CKD and control groups. Comparing BMSCs with ASCs, gene expression of Bglap, Bmp4, Igf1, Itgax, Pparg, Ptprc, and Tnf were up-regulated, while Col1a1, Mmp2, Sox9, and Vegfa were down-regulated in both CKD and control groups. Uremic toxin in CKD rats had a small effect on the gene expression and differentiation of MSCs. However, long-term exposure to uremic toxin and the differences in gene expression of MSCs derived from bone marrow or adipose tissue may affect renal regeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Yokoo T, Ohashi T, Shen J-S, et al. Human mesenchymal stem cells in rodent whole embryo culture are reprogrammed to contribute kidney tissues. Proc Natl Acad Sci USA. 2005;102:3296–300.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Yokoo T, Fukui A, Ohashi T, et al. Xenobiotic kidney organogenesis from human mesenchymal stem cells using a growing rodent embryo. J Am Soc Nephrol. 2006;17:1026–34.

    Article  PubMed  Google Scholar 

  3. Yokoo T, Fukui A, Matsumoto K, et al. Generation of transplantable erythropoietin producer derived from human mesenchymal stem cells. Transplantation. 2008;85:1654–8.

    Article  PubMed  CAS  Google Scholar 

  4. Gliaser M. Growth characteristics of circulating hematopoietic progenitors in terminal renal failure. Med Sci Monit. 2006;12:CR113–117.

    Google Scholar 

  5. Drewa T, Joachimiak R, Kaznica A, Flisinski M, Brymora A, Manitius J. Bone marrow progenitors from animals with chronic renal failure lack capacity of in vitro proliferation. Transplant Proc. 2008;40:1668–73.

    Article  PubMed  CAS  Google Scholar 

  6. Noh H, Yu MR, Kim HJ, et al. Uremia induces functional incompetence of bone marrow-derived stromal cells. Nephrol Dial Transplant. 2012;27:218–25.

    Article  PubMed  CAS  Google Scholar 

  7. Roemeling-van Rhijn M, Reinders ME, de Klein A, et al. Mesenchymal stem cells derived from adipose tissue are not affected by renal disease. Kidney Int. 2012. doi:10.1038/ki.2012.187.

  8. Zuk PA, Zhu M, Mizuno H, et al. Multi-lineage cells from human adipose tissue: implication for cell- based therapies. Tissue Eng. 2001;7:211–28.

    Article  PubMed  CAS  Google Scholar 

  9. Kanazawa H, Fujimoto Y, Teratani T, et al. Bone marrow-derived mesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model. PLoS ONE. 2011;. doi:10.1371/journal.pone.0019195.

    Google Scholar 

  10. Shimada Y, Nishida H, Nishiyama Y, et al. Proteasome inhibitors improve the function of mutant lysosomal alpha-glucosidase in fibroblasts from Pompe disease patient carrying c.546G>T mutation. Biochem Biophys Res Commun. 2011;415:274–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a Grant-in-Aid for Progressive Renal Diseases Research, Research on Intractable Disease, from the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest

The authors have declared that no conflict of interest exists.

Author information

Authors and Affiliations

  1. Project Laboratory for Kidney Regeneration, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Akifumi Yamada, Takashi Yokoo, Shinya Yokote, Shuichiro Yamanaka, Luna Izuhara & Yuichi Katsuoka

  2. Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan

    Akifumi Yamada, Akinori Shukuya, Toya Ohashi & Hiroyuki Ida

  3. Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Takashi Yokoo, Shinya Yokote & Shuichiro Yamanaka

  4. Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Luna Izuhara & Hirotaka James Okano

  5. Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Yohta Shimada, Toya Ohashi & Hiroyuki Ida

Authors
  1. Akifumi Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Yokoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shinya Yokote
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shuichiro Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luna Izuhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuichi Katsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yohta Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Akinori Shukuya
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hirotaka James Okano
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Toya Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hiroyuki Ida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takashi Yokoo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamada, A., Yokoo, T., Yokote, S. et al. Comparison of multipotency and molecular profile of MSCs between CKD and healthy rats. Human Cell 27, 59–67 (2014). https://doi.org/10.1007/s13577-013-0082-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-013-0082-7

Keywords

Search

Navigation