Tissue-Specific Stem Cells

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Non Cell-Autonomous Reprogramming of Adult Ocular Progenitors: Generation of Pluripotent Stem Cells without Exogenous Transcription Factors†‡§

  1. Sudha Balasubramanian1,
  2. Norbert Babai1,
  3. Anathbandhu Chaudhuri1,
  4. Fang Qiu2,
  5. Sumitra Bhattacharya1,
  6. Bhavana J. Dave3,
  7. Sowmya Parameswaran1,
  8. Steve D. Carson5,
  9. Wallace B Thoreson1,
  10. John G. Sharp4,
  11. Mahendra Rao5,
  12. Iqbal Ahmad1,¶,*

Article first published online: 26 OCT 2009

DOI: 10.1002/stem.242

Issue

STEM CELLS

STEM CELLS

Volume 27, Issue 12, pages 3053–3062, December 2009

Additional Information

How to Cite

Balasubramanian, S., Babai, N., Chaudhuri, A., Qiu, F., Bhattacharya, S., Dave, B. J., Parameswaran, S., Carson, S. D., Thoreson, W. B., Sharp, J. G., Rao, M. and Ahmad, I. (2009), Non Cell-Autonomous Reprogramming of Adult Ocular Progenitors: Generation of Pluripotent Stem Cells without Exogenous Transcription Factors. STEM CELLS, 27: 3053–3062. doi: 10.1002/stem.242

Author Information

  1. 1

    Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198

  2. 2

    Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska 68198

  3. 3

    Human Genetics Laboratory, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198

  4. 4

    Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198

  5. 5

    Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, Research in Regenerative Medicine and Stem Cell Technology, Invitrogen Corporation

  1. Telephone: 402-559-4091; Fax: 402-559-3238

*Department of Ophthalmology and Visual Sciences, 98-5840 University of Nebraska Medical Center, Omaha, NE 68198-5840

  1. †

    Author contributions: S. Balasubramanian: collection and assembly of data; data analysis and interpretation; manuscript writing; N.B., A.C., S. Bhattacharya, and S.P.: collection and assembly of data; F.Q., W.B.T., and M.R.: data analysis and interpretation; B.D. and S.C.: collection and assembly of data; data analysis and interpretation; J.G.S.: provision of study materials; data analysis and interpretation; I.A.: conception and design; data analysis and interpretation; manuscript writing.

  2. ‡

    First published online in STEM CELLS EXPRESS October 26, 2009.

  3. §

    Disclosure of potential conflicts of interest is found at the end of this article.

Publication History

  1. Issue published online: 14 DEC 2009
  2. Article first published online: 26 OCT 2009
  3. Accepted manuscript online: 26 OCT 2009 12:00AM EST
  4. Manuscript Accepted: 12 OCT 2009
  5. Manuscript Received: 9 SEP 2009

Funded by

  • Lincy Foundation, Nebraska Department of Human and Health Services
  • Pearson Foundation
  • Nebraska Tobacco Fund for Biomedical Research

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Keywords:

  • Reprogramming;
  • Induced pluripotency;
  • iPS;
  • Pluripotent stem cells;
  • Progenitor cells;
  • Hepatocyte differentiation;
  • Cardiac;
  • Neural induction

Abstract

Direct reprogramming of differentiated cells to induced pluripotent stem (iPS) cells by ectopic expression of defined transcription factors (TFs) represents a significant breakthrough towards the use of stem cells in regenerative medicine (Takahashi and Yamanaka Cell 2006;126:663–676). However, the virus-mediated expression of exogenous transcription factors could be potentially harmful and, therefore, represents a barrier to the clinical use of iPS cells. Several approaches, ranging from plasmid-mediated TF expression to introduction of recombinant TFs (Yamanaka Cell 2009;137:13–17; Zhou, Wu, Joo et al. Cell Stem Cell 2009;4:381–384), have been reported to address the risk associated with viral integration. We describe an alternative strategy of reprogramming somatic progenitors entirely through the recruitment of endogenous genes without the introduction of genetic materials or exogenous factors. To this end, we reprogrammed accessible and renewable progenitors from the limbal epithelium of adult rat eye by microenvironment-based induction of endogenous iPS cell genes. Non cell-autonomous reprogramming generates cells that are pluripotent and capable of differentiating into functional neurons, cardiomyocytes, and hepatocytes, which may facilitate autologous cell therapy to treat degenerative diseases. STEM CELLS 2009;27:3053–3060

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