Nerve growth factor plays a role in the neurotherapeutic effect of a CD45 + pan-hematopoietic subpopulation derived from human umbilical cord blood in a traumatic brain injury model

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Abstract

Background aims: Human umbilical cord blood (HUCB) is an important source of stem cells for therapy of hematopoietic disorders and is a potential therapy for various neurological disorders, including traumatic brain injury (TBI). The expression of nerve growth factor (NGF) and its receptors TrkA, p75 NTR and α9β1 integrin on an HUCB CD45 + pan-hematopoietic subpopulation was investigated in the context of its neurotherapeutic potential after TBI. Methods: NGF and its receptors were detected on CD45 + cells by reverse transcriptase polymerase chain reaction, flow cytometry analysis and confocal microscopy. CD45 + cells were stimulated by TBI brain extracts, and NGF levels were measured by enzyme-linked immunosorbent assay. TBI mice were divided into six groups for xenogeneic intravenous transplantation, 1 day post-trauma, with 1 × 10 6 CD45 + cells untreated or treated with the anti-NGF neutralizing antibody K252a, a TrkA antagonist; VLO5, an α9β1 disintegrin; or negative (vehicle) and positive (NGF) controls. Results: The HUCB CD45 + subpopulation constitutively expresses NGF and its receptors, mainly TrkA and p75 NTR and minor levels of α9β1. In vitro experiments provided evidence that trauma-related mediators from brain extracts of TBI mice induced release of NGF from HUCB CD45 + cell cultures. HUCB CD45 + cells induced a neurotherapeutic effect in TBI mice, abrogated by cell treatment with either anti-NGF antibody or K252a, but not VLO5. Conclusions: These findings strengthen the role of NGF and its TrkA receptor in the HUCB CD45 + subpopulation's neurotherapeutic effect. The presence of neurotrophin receptors in the HUCB CD45 + pan-hematopoietic subpopulation may explain the neuroprotective effect of cord blood in therapy of a variety of neurological disorders.

Original languageEnglish
Pages (from-to)245-261
Number of pages17
JournalCytotherapy
Volume20
Issue number2
DOIs
StatePublished - Feb 2018

Bibliographical note

Publisher Copyright:
© 2017 International Society for Cellular Therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • CD45 pan-hematopoietic subpopulation
  • TBI
  • TrkA receptor
  • cord blood
  • nerve growth factor
  • neuroinflammation
  • neurotherapeutic effect

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