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Generation of systemic lupus erythematosus-specific induced pluripotent stem cells from urine

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Abstract

Systemic lupus erythematosus (SLE) is the prototype of complex autoimmune diseases characterized by the production of autoantibodies which results in widespread immunologic abnormalities and immune complex formation. The underlying etiology remains largely unknown. When progressing toward kidney failure, it is becoming a serious public health problem. Kidney transplantation is a feasible therapy, but significant limitations were existed, including shortage of donor organs and lack of funding. To find an alternative proposal for kidney replacement, the induced pluripotent stem cells (iPSCs) technology was adopted. We identified typical SLE patients. Lentiviral transduction of OCT4, SOX2, KLF4, and c-MYC, under feeder conditions, resulted in reprogramming of urine-derived renal tubular cells. We investigated the viability of iPSCs generation from patients with SLE by identification of totipotency and pluripotency. SLE patient renal tubular cells–derived iPSCs exhibited properties of human embryonic stem cells, including morphology, growth properties, alkaline phosphatase, expression of pluripotency, genes and surface markers, and teratoma formation. We demonstrated that generation of SLE-specific iPSCs from urine was not only the first time worldwide, but was feasible and efficient. IPSCs from SLE would provide convenient model to study disease pathogenesis, drugs screening, and gene therapy.

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References

  1. Postal M, Costallat LT, Appenzeller S (2012) Biological therapy in systemic lupus erythematosus. Int J Rheumatol 2012:578641

    PubMed  Google Scholar 

  2. Baddour JA, Sousounis K, Tsonis PA (2012) Organ repair and regeneration: an overview. Birth Defects Res C Embryo Today 96(1):1–29

    Article  PubMed  CAS  Google Scholar 

  3. Maherali N, Hochedlinger K (2008) Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell 3(6):595–605

    Article  PubMed  CAS  Google Scholar 

  4. Zhou T, Benda C, Duzinger S, Huang Y, Li X, Li Y et al (2011) Generation of induced pluripotent stem cells from urine. J Am Soc Nephrol 22(7):1221–1228

    Article  PubMed  Google Scholar 

  5. Thatava T, Armstrong AS, De Lamo JG, Edukulla R, Khan YK, Sakuma T et al (2011) Successful disease-specific induced pluripotent stem cell generation from patients with kidney transplantation. Stem Cell Res Ther 2(6):48

    Article  PubMed  CAS  Google Scholar 

  6. Hanly JG, Urowitz MB, Su L, Gordon C, Bae SC, Sanchez-Guerrero J et al (2012) Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study. Ann Rheum Dis 71(9):1502–1509

    Google Scholar 

  7. Touma Z, Gladman DD, Ibanez D, Taghavi-Zadeh S, Urowitz MB (2011) Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 enhances the ability of SLE Responder Index to identify responders in clinical trials. J Rheumatol 38(11):2395–2399

    Article  PubMed  Google Scholar 

  8. Song B, Niclis JC, Alikhan MA, Sakkal S, Sylvain A, Kerr PG et al (2011) Generation of induced pluripotent stem cells from human kidney mesangial cells. J Am Soc Nephrol 22(7):1213–1220

    Article  PubMed  CAS  Google Scholar 

  9. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872

    Article  PubMed  CAS  Google Scholar 

  10. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920

    Article  PubMed  CAS  Google Scholar 

  11. Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F et al (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26(11):1276–1284

    Article  PubMed  CAS  Google Scholar 

  12. Giorgetti A, Montserrat N, Aasen T, Gonzalez F, Rodriguez-Piza I, Vassena R et al (2009) Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell 5(4):353–357

    Article  PubMed  CAS  Google Scholar 

  13. Esteban MA, Wang T, Qin B, Yang J, Qin D, Cai J et al (2010) Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6(1):71–79

    Article  PubMed  CAS  Google Scholar 

  14. Cai J, Li W, Su H, Qin D, Yang J, Zhu F et al (2010) Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells. J Biol Chem 285(15):11227–11234

    Article  PubMed  CAS  Google Scholar 

  15. Haase A, Olmer R, Schwanke K, Wunderlich S, Merkert S, Hess C et al (2009) Generation of induced pluripotent stem cells from human cord blood. Cell Stem Cell 5(4):434–441

    Article  PubMed  CAS  Google Scholar 

  16. Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P et al (2010) Epigenetic memory in induced pluripotent stem cells. Nature 467(7313):285–290

    Article  PubMed  CAS  Google Scholar 

  17. Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Narva E et al (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471(7336):58–62

    Article  PubMed  CAS  Google Scholar 

  18. Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J et al (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471(7336):63–67

    Article  PubMed  CAS  Google Scholar 

  19. Cheng D, Lei L, Lu Z, Li Z, Wang H (2010) Induction and characterization of induced pluripotent stem (iPS) cells: a review. Sheng Wu Gong Cheng Xue Bao 26(4):421–430

    PubMed  CAS  Google Scholar 

  20. Chen J, Liu J, Chen Y, Yang J, Liu H, Zhao X et al (2011) Rational optimization of reprogramming culture conditions for the generation of induced pluripotent stem cells with ultra-high efficiency and fast kinetics. Cell Res 21(6):884–894

    Article  PubMed  CAS  Google Scholar 

  21. Dai Y, Zhang L, Hu C, Zhang Y (2010) Genome-wide analysis of histone H3 lysine 4 trimethylation by ChIP-chip in peripheral blood mononuclear cells of systemic lupus erythematosus patients. Clin Exp Rheumatol 28(2):158–168

    PubMed  CAS  Google Scholar 

  22. Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J et al (2010) Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 20(2):170–179

    Article  PubMed  CAS  Google Scholar 

  23. Yeagy BA, Cherqui S (2011) Kidney repair and stem cells: a complex and controversial process. Pediatr Nephrol 26(9):1427–1434

    Article  PubMed  Google Scholar 

  24. Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY et al (2010) Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 28(8):848–855

    Article  PubMed  CAS  Google Scholar 

  25. Tyndall A (2011) Successes and failures of stem cell transplantation in autoimmune diseases. Hematology Am Soc Hematol Educ Program 2011:280–284

    Article  PubMed  Google Scholar 

  26. Kobayashi T, Tanaka H, Kuwana H, Inoshita S, Teraoka H, Sasaki S et al (2005) Wnt4-transformed mouse embryonic stem cells differentiate into renal tubular cells. Biochem Biophys Res Commun 336(2):585–595

    Article  PubMed  CAS  Google Scholar 

  27. Griesche N, Bereiter-Hahn J, Geiger H, Schubert R, Baer PC (2012) During epithelial differentiation of human adipose-derived stromal/stem cells, expression of zonula occludens protein-1 is induced by a combination of retinoic acid, activin-A and bone morphogenetic protein-7. Cytotherapy 14(1):61–69

    Article  PubMed  CAS  Google Scholar 

  28. Vigneau C, Polgar K, Striker G, Elliott J, Hyink D, Weber O et al (2007) Mouse embryonic stem cell-derived embryoid bodies generate progenitors that integrate long term into renal proximal tubules in vivo. J Am Soc Nephrol 18(6):1709–1720

    Article  PubMed  CAS  Google Scholar 

  29. Batchelder CA, Lee CC, Matsell DG, Yoder MC, Tarantal AF (2009) Renal ontogeny in the rhesus monkey (Macaca mulatta) and directed differentiation of human embryonic stem cells towards kidney precursors. Differentiation 78(1):45–56

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the Key Project for Science and Technology of Shenzhen (project no. 201001006) and the General Program of National Natural Science Foundation China (30972741/C080701). This work was supported by the Guangzhou Institutes of Biomedicine and Health (in Guangzhou, China). We thank all members of laboratories for helpful suggestions, especially Dr. Qin Dajiang, and all the patients and healthy volunteers who participated in this study.

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The authors declare that they have no conflict of interest.

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Correspondence to Yong Dai.

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Chen, Y., Luo, R., Xu, Y. et al. Generation of systemic lupus erythematosus-specific induced pluripotent stem cells from urine. Rheumatol Int 33, 2127–2134 (2013). https://doi.org/10.1007/s00296-013-2704-5

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  • DOI: https://doi.org/10.1007/s00296-013-2704-5

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