Generation of HIV-1 resistant and functional macrophages from hematopoietic stem cell-derived induced pluripotent stem cells

Amal Kambal, Gaela Mitchell, Whitney Cary, William Gruenloh, Yunjoon Jung, Stefanos Kalomoiris, Catherine Nacey, Jeannine McGee, Matt Lindsey, Brian Fury, Gerhard Bauer, Jan Nolta, Joseph S Anderson

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48 Scopus citations

Abstract

Induced pluripotent stem cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from adult individuals. By developing iPSCs to treat HIV, there is the potential for generating a continuous supply of therapeutic cells for transplantation into HIV-infected patients. In this study, we have used human hematopoietic stem cells (HSCs) to generate anti-HIV gene expressing iPSCs for HIV gene therapy. HSCs were dedifferentiated into continuously growing iPSC lines with four reprogramming factors and a combination anti-HIV lentiviral vector containing a CCR5 short hairpin RNA (shRNA) and a human/rhesus chimeric TRIM5α gene. Upon directed differentiation of the anti-HIV iPSCs toward the hematopoietic lineage, a robust quantity of colony-forming CD133+ HSCs were obtained. These cells were further differentiated into functional end-stage macrophages which displayed a normal phenotypic profile. Upon viral challenge, the anti-HIV iPSC-derived macrophages exhibited strong protection from HIV-1 infection. Here, we demonstrate the ability of iPSCs to develop into HIV-1 resistant immune cells and highlight the potential use of iPSCs for HIV gene and cellular therapies.

Original languageEnglish (US)
Pages (from-to)584-593
Number of pages10
JournalMolecular Therapy
Volume19
Issue number3
DOIs
StatePublished - Mar 2011

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ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Kambal, A., Mitchell, G., Cary, W., Gruenloh, W., Jung, Y., Kalomoiris, S., Nacey, C., McGee, J., Lindsey, M., Fury, B., Bauer, G., Nolta, J., & Anderson, J. S. (2011). Generation of HIV-1 resistant and functional macrophages from hematopoietic stem cell-derived induced pluripotent stem cells. Molecular Therapy, 19(3), 584-593. https://doi.org/10.1038/mt.2010.269