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Method of Inducing Pluripotent or Multipotent Stem Cells by Blocking CD47 Receptor Signaling

Posted Jun 27 2013 8:00pm

Description of Invention:
NIH researchers have discovered that blockade of the signaling activity of a single cell-surface receptor, CD47, without transfection or introduction of potentially transforming viral vectors, results in high frequency, spontaneous generation of self-renewing cells with a high proliferative capacity. Induced pluripotent stem cells (iPS cells) are currently produced by transforming cells with viral or other constitutive expression vectors encoding four stem cell transcription factors (c-Myc, Sox2, Klf4, and Oct4), but this method presents challenges such as over-expression of c-Myc, which can result in malignant transformation. The present invention relates to a method of using CD47-modulating compounds to induce multipotent stem cells without the concomitant risk of malignant transformation and without requiring the use of feeder cells. The cellular phenotypes are associated with increased expression of the hallmark stem cell-inducing transcription factors, c-Myc, Sox2, Klf4, and Oct4. The current invention builds on the NIH's previous discoveries of antibodies, antisense morpholino oligonucleotides, peptide compounds and other small molecules that modulate CD47.

Applications:
Regenerative medicine and stem cell therapy.

Advantages:
  • Does not require use of viral vectors
  • Eliminates risk of malignant transformation for clinical applications
  • Eliminates need for feeder cells
  • Allows generation and maintenance of a ready supply of iPS cells using a single defined agent
  • Avoids loss of differentiated phenotype associated with telomerase or T antigen transfection


Development Status:
  • In vitro data available
  • In vivo data available (animal)


Inventors:
Sukhbir Kaur (NCI)
David D Roberts (NCI)
Jeff S Isenberg (NCI)


Patent Status:
HHS, Reference No. E-086-2012/1
US, Application No. 61/735,701 filed 11 Dec 2012
PCT, Application No. PCT/US2013/035838 filed 09 Apr 2013


Related Technologies:
US, Patent No. 8,236,313, Issued 07 Aug 2012, Reference No. E-227-2006/5
US, Application No. 13/546,931 filed 11 Jul 2012, Reference No. E-227-2006/5
US, Application No. 13/546,941 filed 11 Jul 2012, Reference No. E-227-2006/5


Relevant Publication:
  1. Kaur S, et al. [ PMID 23591719 ]
  2. NCI News Note: A drug target that stimulates development of healthy stem cells. 2013 Apr 17. [ NCI News Note ]


Collaborative Research Opportunity:
The National Cancer Institute, Center for Cancer Research, Laboratory of Pathology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize CD47 modulators for regenerative medicine and stem cell therapy applications. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov . Click here to view the NCI collaborative opportunity announcement.


For Licensing Information Please Contact:
Charlene Sydnor Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: sydnorc@mail.nih.gov
Phone: 301-435-4689
Fax: 301-402-0220


Ref No: 2582

Updated: 06/2013

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