Efficient Generation of Integration-Free iPS Cells from Human Adult Peripheral Blood Using BCL-XL Together with Yamanaka Factors

Rui Jun Su, David J. Baylink, Amanda Neises, Jason B. Kiroyan, Xianmei Meng, Kimberly J. Payne, Benjamin Tschudy-Seney, YuYou Duan, Nancy Appleby, Mary Kearns-Jonker, Daila S. Gridley, Jun Wang, K. H William Lau, Xiao Bing Zhang

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

The ability to efficiently generate integration-free induced pluripotent stem cells (iPSCs) from the most readily available source-peripheral blood-has the potential to expedite the advances of iPSC-based therapies. We have successfully generated integration-free iPSCs from cord blood (CB) CD34+ cells with improved oriP/EBNA1-based episomal vectors (EV) using a strong spleen focus forming virus (SFFV) long terminal repeat (LTR) promoter. Here we show that Yamanaka factors (OCT4, SOX2, MYC, and KLF4)-expressing EV can also reprogram adult peripheral blood mononuclear cells (PBMNCs) into pluripotency, yet at a very low efficiency. We found that inclusion of BCL-XL increases the reprogramming efficiency by approximately 10-fold. Furthermore, culture of CD3-/CD19- cells or T/B cell-depleted MNCs for 4-6 days led to the generation of 20-30 iPSC colonies from 1 ml PB, an efficiency that is substantially higher than previously reported. PB iPSCs express pluripotency markers, form teratomas, and can be induced to differentiate in vitro into mesenchymal stem cells, cardiomyocytes, and hepatocytes. Used together, our optimized factor combination and reprogramming strategy lead to efficient generation of integration-free iPSCs from adult PB. This discovery has potential applications in iPSC banking, disease modeling and regenerative medicine.

Original languageEnglish (US)
Article numbere64496
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 21 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Su, R. J., Baylink, D. J., Neises, A., Kiroyan, J. B., Meng, X., Payne, K. J., Tschudy-Seney, B., Duan, Y., Appleby, N., Kearns-Jonker, M., Gridley, D. S., Wang, J., Lau, K. H. W., & Zhang, X. B. (2013). Efficient Generation of Integration-Free iPS Cells from Human Adult Peripheral Blood Using BCL-XL Together with Yamanaka Factors. PLoS One, 8(5), [e64496]. https://doi.org/10.1371/journal.pone.0064496