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

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 alpha 9 beta 1 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 x 10(6) CD45(+) cells untreated or treated with the anti-NGF neutralizing antibody K252a, aTrkA antagonist; VLO5, an alpha 9 beta 1 disintegrin; or negative (vehicle) and positive (NGF) controls. Results. The HUCB CD45(+) subpopulation constitutively expresses NGF and its receptors, mainly TrkA and p75NTR and minor levels of alpha 9 beta 1. 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.