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

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, p75NTR 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 × 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.

RESULTS:

The HUCB CD45+ subpopulation constitutively expresses NGF and its receptors, mainly TrkA and p75NTR 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.

• Authors: Galit Gincberg, Esther Shohami, Victoria Trembovler, Alexander G Alexandrovich, Philip Lazarovici, Uriel Elchalal
• Journal: Cytotherapy (Cytotherapy) Vol. 20 Issue 2 Pg. 245-261 (02 2018) ISSN: 1477-2566 [Electronic] England
• PMID: 29274773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Chemokine CCL3
• RNA, Messenger
• Receptors, Nerve Growth Factor
• Tissue Extracts
• Interleukin-10
• Nerve Growth Factor
• Leukocyte Common Antigens

Topics

• Animals
• Brain Injuries, Traumatic (pathology, therapy)
• Chemokine CCL3 (metabolism)
• Fetal Blood (cytology)
• Hematopoietic Stem Cell Transplantation
• Hematopoietic Stem Cells (cytology)
• Humans
• Interleukin-10 (metabolism)
• Leukocyte Common Antigens (metabolism)
• Mice, Inbred C57BL
• Nerve Growth Factor (genetics, metabolism, therapeutic use)
• RNA, Messenger (genetics, metabolism)
• Receptors, Nerve Growth Factor (genetics, metabolism)
• Tissue Extracts