Abstract
At present, no effective clinical treatment is available for the late effects of radiation myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy. An irradiated cervical spinal cord rat model was generated. UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irradiation. Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining. The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord. Multiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord. Multiple injections of UC-MSCs via the tail vein in a rat model of radiation myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects.
Highlights
The spinal cord is a well-known example of “late-reacting” tissue in response to irradiation [1]
The surface markers of the umbilical cord-derived mesenchymal stromal cells (UC-mesenchymal stromal cell (MSC)) were examined by flow cytometry
UC-MSC administration improved locomotion recovery To determine the potential benefit of the UC-MSC infusion on the spinal cord after irradiation, behavioral tests were performed using the forelimb paralysis scoring system
Summary
The spinal cord is a well-known example of “late-reacting” tissue in response to irradiation [1]. The late effects of radiation myelopathy (i.e., those occurring 6 months to several years after treatment) can be extremely severe and may seriously decrease the patient’s quality of life. These effects are dangerous because they are generally irreversible [3,4]. The vascular endothelial cell population has been proposed as one of the most critical targets of the late effects of radiation myelopathy [9]. No effective clinical treatment is available for the late effects of radiation myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy
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