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.

Abstract

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. 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 × 10⁶ 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. 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. 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.