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

Research output: Contribution to journalArticle

48 Citations (Scopus)

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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Induced Pluripotent Stem Cells
Hematopoietic Stem Cells
HIV-1
Macrophages
HIV
Genetic Therapy
Pluripotent Stem Cells
Regenerative Medicine
Cell Transplantation
Small Interfering RNA
Genes
HIV Infections
Cell Line

ASJC Scopus subject areas

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

Cite this

Generation of HIV-1 resistant and functional macrophages from hematopoietic stem cell-derived induced pluripotent stem cells. / Kambal, Amal; Mitchell, Gaela; Cary, Whitney; Gruenloh, William; Jung, Yunjoon; Kalomoiris, Stefanos; Nacey, Catherine; McGee, Jeannine; Lindsey, Matt; Fury, Brian; Bauer, Gerhard; Nolta, Jan; Anderson, Joseph S.

In: Molecular Therapy, Vol. 19, No. 3, 03.2011, p. 584-593.

Research output: Contribution to journalArticle

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, JS 2011, 'Generation of HIV-1 resistant and functional macrophages from hematopoietic stem cell-derived induced pluripotent stem cells', Molecular Therapy, vol. 19, no. 3, pp. 584-593. https://doi.org/10.1038/mt.2010.269
Kambal, Amal ; Mitchell, Gaela ; Cary, Whitney ; Gruenloh, William ; Jung, Yunjoon ; Kalomoiris, Stefanos ; Nacey, Catherine ; McGee, Jeannine ; Lindsey, Matt ; Fury, Brian ; Bauer, Gerhard ; Nolta, Jan ; Anderson, Joseph S. / Generation of HIV-1 resistant and functional macrophages from hematopoietic stem cell-derived induced pluripotent stem cells. In: Molecular Therapy. 2011 ; Vol. 19, No. 3. pp. 584-593.
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