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

Suman Kanji, Manjusri Das, Reeva Aggarwal, Jingwei Lu, Matthew Joseph, Vincent J. Pompili, Hiranmoy Das

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)685-697
Number of pages13
JournalJournal of cellular and molecular medicine
Volume18
Issue number4
DOIs
StatePublished - Apr 2014

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Nanofibers
Inbred NOD Mouse
SCID Mice
Cell- and Tissue-Based Therapy
Fetal Blood
Skin
Wounds and Injuries
Fibroblasts
Wound Healing
Collagen
Proteasome Inhibitors
JNK Mitogen-Activated Protein Kinases
Coculture Techniques
Collagen Type I
Matrix Metalloproteinases
Cardiomyopathies
Cell Movement

Keywords

  • Collagen
  • Cutaneous wound
  • Human umbilical cord blood
  • MMPs
  • NOD/SCID mice

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy accelerates cutaneous wound closure in NOD/SCID mice. / Kanji, Suman; Das, Manjusri; Aggarwal, Reeva; Lu, Jingwei; Joseph, Matthew; Pompili, Vincent J.; Das, Hiranmoy.

In: Journal of cellular and molecular medicine, Vol. 18, No. 4, 04.2014, p. 685-697.

Research output: Contribution to journalArticle

Kanji, Suman ; Das, Manjusri ; Aggarwal, Reeva ; Lu, Jingwei ; Joseph, Matthew ; Pompili, Vincent J. ; Das, Hiranmoy. / Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy accelerates cutaneous wound closure in NOD/SCID mice. In: Journal of cellular and molecular medicine. 2014 ; Vol. 18, No. 4. pp. 685-697.
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