Abstract
Several studies have reported that human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) restore neurological damage in vivo through their secretion of paracrine factors. We previously found that UC-MSCs attenuate brain injury by secreting neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and hepatocyte growth factor (HGF). However, how these factors contribute to neuroprotection remains unknown. In this study, we aimed to investigate to what extent UC-MSC-derived HGF and BDNF contribute to neuroprotection using a Transwell co-culture system of neonatal cortical neurons damaged by oxygen-glucose deprivation. The influence of HGF and BDNF were determined by investigating neurons in both the presence and absence of UC-MSCs as these cells consistently secrete both factors and can be blocked by neutralizing antibodies. In the co-culture, UC-MSCs significantly improved neuronal injury, as indicated by an increase in immature neuron number, neurite outgrowth, and cell proliferation. Co-culture of damaged neurons with UC-MSCs also exhibited a reduction in the number of neurons displaying signs of apoptosis/necrosis. The neuroprotective actions of UC-MSCs were partially reverted by neutralizing antibodies. Together, our findings reveal that UC-MSC-secreted HGF and BDNF have neuroprotective effects on damaged neurons. Further studies should address the existence of other potential neurotrophic paracrine factors.
Highlights
Mesenchymal stromal cells (MSCs) can be isolated from several sources, including bone marrow, cord blood, adipose tissue, the placenta, and the umbilical cord (UC) [1,2,3,4,5]
We previously reported that intravenously administered UC-derived MSCs (UC-MSCs) attenuate intraventricular hemorrhage-induced injuries, and brain-derived neurotrophic factor (BDNF) and hepatocyte growth factor (HGF) concentration were elevated in serum and cerebrospinal fluid in some part of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) administered mice [8]
Using a multiplex flow cytometry bead assay to analyze HGF and BDNF concentrations in medium containing UC-MSCs confirmed that both factors were constitutively secreted from UC-MSCs, and that their concentrations varied by UC-MSC lot (n = 3, Figure 1D)
Summary
Mesenchymal stromal cells (MSCs) can be isolated from several sources, including bone marrow, cord blood, adipose tissue, the placenta, and the umbilical cord (UC) [1,2,3,4,5]. Among various sources of MSCs, we focused on the UC for the following reasons: [1] abundant sources and ease of collection, storage, and transport; [2] no invasive process of collection; [3] little ethical controversy; [4] multipotency to differentiate into various cell types; [5] low immunogenicity with significant immunosuppressive ability; and [6] migration ability toward injured sites [5]. UC-MSCs have been reported to exert anti-inflammatory effects via contact with activated T cells and partly through indoleamine 2, 3dioxygenase and prostaglandin E2 [6, 7]. It is thought that UC-MSCs exert anti-inflammatory actions on brain lesions in the acute stages of injury. The mechanisms which underlie the neurotrophic effects of UC-MSCs have not been fully elucidated
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