Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells

Nancy Villa, Swarna Bais, Winnie M. Chan, Amy M. Meacham, Elizabeth Wise, Masmudur Rahman, Jan S. Moreb, Emma H. Rosenau, John R. Wingard, Douglas McFadden, Christopher R. Cogle

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy. Methods Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC-IC) assay and colony-forming cell (CFC) assay. Results MYXV initiated infection in up to 45% of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95% of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10% of CD34+ cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation. Conclusions Human hematopoietic cells are non-permissive for MYXV. Human hematopoietic stem and progenitor cells were not infected and thus unaffected by MYXV ex vivo treatment.

Original languageEnglish (US)
Pages (from-to)465-480
Number of pages16
JournalCytotherapy
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Fingerprint

Myxoma virus
Hematopoietic Stem Cells
Virus Diseases
Hematologic Neoplasms
Transplants
Cell Culture Techniques
Cell Count
Oncolytic Viruses
Therapeutics
Temperature
Cell Transplantation

Keywords

  • bone marrow
  • mobilized peripheral stem cell blood
  • myxoma virus
  • purging
  • virotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

Cite this

Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells. / Villa, Nancy; Bais, Swarna; Chan, Winnie M.; Meacham, Amy M.; Wise, Elizabeth; Rahman, Masmudur; Moreb, Jan S.; Rosenau, Emma H.; Wingard, John R.; McFadden, Douglas; Cogle, Christopher R.

In: Cytotherapy, Vol. 18, No. 3, 01.03.2016, p. 465-480.

Research output: Contribution to journalArticle

Villa, N, Bais, S, Chan, WM, Meacham, AM, Wise, E, Rahman, M, Moreb, JS, Rosenau, EH, Wingard, JR, McFadden, D & Cogle, CR 2016, 'Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells', Cytotherapy, vol. 18, no. 3, pp. 465-480. https://doi.org/10.1016/j.jcyt.2015.12.007
Villa, Nancy ; Bais, Swarna ; Chan, Winnie M. ; Meacham, Amy M. ; Wise, Elizabeth ; Rahman, Masmudur ; Moreb, Jan S. ; Rosenau, Emma H. ; Wingard, John R. ; McFadden, Douglas ; Cogle, Christopher R. / Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells. In: Cytotherapy. 2016 ; Vol. 18, No. 3. pp. 465-480.
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abstract = "Background Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy. Methods Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC-IC) assay and colony-forming cell (CFC) assay. Results MYXV initiated infection in up to 45{\%} of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95{\%} of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10{\%} of CD34+ cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation. Conclusions Human hematopoietic cells are non-permissive for MYXV. Human hematopoietic stem and progenitor cells were not infected and thus unaffected by MYXV ex vivo treatment.",
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AU - Villa, Nancy

AU - Bais, Swarna

AU - Chan, Winnie M.

AU - Meacham, Amy M.

AU - Wise, Elizabeth

AU - Rahman, Masmudur

AU - Moreb, Jan S.

AU - Rosenau, Emma H.

AU - Wingard, John R.

AU - McFadden, Douglas

AU - Cogle, Christopher R.

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N2 - Background Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy. Methods Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC-IC) assay and colony-forming cell (CFC) assay. Results MYXV initiated infection in up to 45% of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95% of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10% of CD34+ cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation. Conclusions Human hematopoietic cells are non-permissive for MYXV. Human hematopoietic stem and progenitor cells were not infected and thus unaffected by MYXV ex vivo treatment.

AB - Background Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy. Methods Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC-IC) assay and colony-forming cell (CFC) assay. Results MYXV initiated infection in up to 45% of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95% of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10% of CD34+ cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation. Conclusions Human hematopoietic cells are non-permissive for MYXV. Human hematopoietic stem and progenitor cells were not infected and thus unaffected by MYXV ex vivo treatment.

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KW - purging

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