Nanofiber-expanded human umbilical cord blood–derived CD34+ cell therapy accelerates cutaneous wound closure in NOD/SCID mice

Authors

  • Suman Kanji,

    1. Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA
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  • Manjusri Das,

    1. Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA
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  • Reeva Aggarwal,

    1. Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA
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  • Jingwei Lu,

    1. Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA
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  • Matthew Joseph,

    1. Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA
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  • Vincent J. Pompili,

    1. Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA
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  • Hiranmoy Das

    Corresponding author
    1. Stem Cell Research Laboratory, Cardiovascular Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA
    • Correspondence to: Hiranmoy DAS, Ph.D., Associate Professor of Internal Medicine, Director, Cardiovascular Stem Cell Laboratories, The Dorothy M. Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, 460 W. 12th Avenue, BRT 382, Columbus, OH 43210, USA.

      Tel.: (614) 688-8711 office

      Fax: (614) 293-5614

      E-mail: hiranmoy.das@osumc.edu

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Abstract

Nanofiber-expanded human umbilical cord blood–derived CD34+ cell therapy has been shown to have potential applications for peripheral and myocardial ischaemic diseases. However, the efficacies of expanded CD34+ cell therapy for treating cutaneous wounds and its mechanisms of action have yet to be established. Using an excisional wound model in non-obese diabetic/severe combined immune deficient mice, we show herein that CD34+ cells accelerate the wound-healing process by enhancing collagen synthesis, and increasing fibroblast cell migration within the wound bed. Concomitantly, reduced levels of matrix metalloproteinase (MMPs) such as MMP1, MMP3, MMP9 and MMP13 were detected in the wound beds of animals treated with CD34+ cells compared with vehicle-treated controls. CD34+ cells were found to mediate enhanced migration and proliferation of dermal fibroblast cells in vitro. Moreover, CD34+ cells secrete collagen in a serum-deprived environment. In mechanistic studies, co-culture of CD34+ cells with primary skin fibroblasts increased the expression of collagen1A1, a component of type 1 collagen, and decreased the expression of MMP1 in fibroblast cells in the presence of a proteasome inhibitor. Finally, CD34+ cell–mediated functions were transcriptionally regulated by the c-Jun N-terminal kinases pathway. Collectively, these data provide evidence of therapeutic efficacy and a novel mechanism of nanofiber-expanded CD34+ cell–mediated accelerated wound healing.

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