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Successfully transfected primary peripherally mobilized human CD34+ hematopoietic stem and progenitor cells (HSPCs) demonstrate increased susceptibility to retroviral infection.

ABSTRACT: Transfection, the process of introducing purified nucleic acids into cells, and viral transduction, viral-mediated nucleic acid transfer, are two commonly utilized techniques for gene delivery in the research setting. Transfection allows purified nucleic acid to be introduced into target cells through chemical-based techniques, nonchemical methods or particle-based methods, while viral transduction employs genomes or vectors based on adenoviruses, retroviruses (e.g. lentiviruses), adeno-associated viruses, or hybrid viruses. Transfected DNAs are often tested for potential effects on subsequent transduction, but it is not clear whether transfection itself rather than the particular nucleic acid being introduced might impact subsequent viral transfection. We observed a significant association between successfully transfected mobilized peripheral blood CD34+ human stem and progenitor cells (HSPCs) and permissiveness to subsequent lentiviral transduction, which was not evident in other cells such as 293?T cells and Jurkat cells. This association, apparently specific to CD34+ human stem and progenitor cells (HSPCs), is critical to both research and clinical applications as these cells are a frequent target of transfection and viral transduction owing to the durable nature of these cells in living systems. This finding may also present a significant opportunity to enhance the success of viral transduction for clinical applications.

SUBMITTER: Sebrow J

PROVIDER: S-EPMC7008578 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Successfully transfected primary peripherally mobilized human CD34+ hematopoietic stem and progenitor cells (HSPCs) demonstrate increased susceptibility to retroviral infection.

Sebrow Jeffrey J Goff Stephen P SP Griffin Daniel O DO

Virology journal 20200210 1

Transfection, the process of introducing purified nucleic acids into cells, and viral transduction, viral-mediated nucleic acid transfer, are two commonly utilized techniques for gene delivery in the research setting. Transfection allows purified nucleic acid to be introduced into target cells through chemical-based techniques, nonchemical methods or particle-based methods, while viral transduction employs genomes or vectors based on adenoviruses, retroviruses (e.g. lentiviruses), adeno-associat ...[more]

PMID: 32039735

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Project description:CD34+-selected stem cell boost (SCB) without conditioning has recently been utilized for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation with promising results. Unfortunately, many patients have been unable to receive the boost infusion as their donors were unwilling or unable to undergo an additional stem cell collection. Therefore, we conducted this study utilizing either fresh or cryopreserved peripheral blood stem cell products to create CD34+-selected boost infusions for the treatment of PGF. Additionally, to explore relationship of CD34+ dose and response, we included a cohort of donors mobilized with plerixafor in addition to the standard granulocyte colony-stimulating factor (G-CSF). Twenty-six patients with PGF were included in this study. Seventeen donor-recipient pairs were enrolled onto the prospective study; an additional 9 patients treated off protocol were reviewed retrospectively. Three different donor products were used for CD34+ selection: (1) fresh mobilized product using G-CSF only, (2) fresh mobilized products using G-CSF and plerixafor, and (3) cryopreserved cells mobilized with G-CSF. CD34+ cell selection was performed using a CliniMACS. The infusion was not preceded by administration of any chemotherapy or conditioning regimen. The primary objective was hematologic response rate and secondary objectives included CD34+ yields, incidence and severity of acute and chronic graft-versus-host disease (GVHD), overall survival (OS), and relapse-free survival (RFS). The median post-selection CD34+ counts per kilogram of recipient weight were 3.1 × 106, 10.9 × 106, and 1 × 106 for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. The median CD34+ yields (defined as the number of CD34+ cells after selection/CD34+ cells before CD34+ selection) were 69%, 66%, and 28% for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. After SCB, 16 of the 26 recipients (62%) had a complete response, including 5 of 8 (63%) who received cryopreserved products. Five had a partial response (19%), resulting in an overall response rate of 81%. One-year RFS and OS were 50% and 65%, respectively. There was no treatment-related toxicity reported other than GVHD: 6 (23%) developed acute GVHD (2 grade I and 4 grade II) and 8 (31%) developed chronic GVHD (2 limited and 6 extensive). Cryopreserved products are viable alternatives to create SCB for the treatment of PGF. When collecting fresh products is an option, the addition of plerixafor increases CD34+ yield over G-CSF alone; however, it is currently unclear if the CD34+ cell dose impacts the efficacy of the SCB.

Dataset Information

Successfully transfected primary peripherally mobilized human CD34+ hematopoietic stem and progenitor cells (HSPCs) demonstrate increased susceptibility to retroviral infection.

Publications

Successfully transfected primary peripherally mobilized human CD34+ hematopoietic stem and progenitor cells (HSPCs) demonstrate increased susceptibility to retroviral infection.

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