Transgene-free disease-specific induced pluripotent stem cells from patients with type 1 and type 2 diabetes

Yogish C Kudva, Seiga Ohmine, Lucas V. Greder, James R. Dutton, Adam Armstrong, Josep Genebriera De Lamo, Yulia Krotova Khan, Tayaramma Thatava, Mamoru Hasegawa, Noemi Fusaki, Jonathan M W Slack, Yasuhiro H Ikeda

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The induced pluripotent stem cell (iPSC) technology enables derivation of patient-specific pluripotent stem cells from adult somatic cells without using an embryonic cell source. Redifferentiation of iPSCs from diabetic patients into pancreatic islets will allow patient-specific disease modeling and autologous cell replacement therapy for failing islets. To date, diabetes-specific iPSCs have been generated from patients with type 1 diabetes using integrating retroviral vectors. However, vector integration into the host genome could compromise the biosafety and differentiation propensities of derived iPSCs. Although various integration-free reprogramming systems have been described, their utility to reprogram somatic cells from patients remains largely undetermined. Here, we used nonintegrating Sendai viral vectors to reprogram cells from patients with type 1 and type 2 diabetes (T2D). Sendai vector infection led to reproducible generation of genomic modification-free iPSCs (SV-iPSCs) from patients with diabetes, including an 85-year-old individual with T2D. SV-iPSCs lost the Sendai viral genome and antigens within 8-12 passages while maintaining pluripotency. Genome-wide transcriptome analysis of SViPSCs revealed induction of endogenous pluripotency genes and downregulation of genes involved in the oxidative stress response and the INK4/ARF pathways, including p16INK4a, p15INK4b, and p21CIP1. SV-iPSCs and iPSCs made with integrating lentiviral vectors demonstrated remarkable similarities in global gene expression profiles. Thus, the Sendai vector system facilitates reliable reprogramming of patient cells into transgene-free iPSCs, providing a pluripotent platform for personalized diagnostic and therapeutic approaches for diabetes and diabetes- associated complications.

Original languageEnglish (US)
Pages (from-to)451-461
Number of pages11
JournalStem cells translational medicine
Volume1
Issue number6
DOIs
StatePublished - 2012

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Keywords

  • Aging
  • Diabetes
  • Induced pluripotency
  • iPS
  • Lentiviral vector

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

Cite this

Kudva, Y. C., Ohmine, S., Greder, L. V., Dutton, J. R., Armstrong, A., De Lamo, J. G., Khan, Y. K., Thatava, T., Hasegawa, M., Fusaki, N., Slack, J. M. W., & Ikeda, Y. H. (2012). Transgene-free disease-specific induced pluripotent stem cells from patients with type 1 and type 2 diabetes. Stem cells translational medicine, 1(6), 451-461. https://doi.org/10.5966/sctm.2011-0044