Preconditioning in lowered oxygen enhances the therapeutic potential of human umbilical mesenchymal stem cells in a rat model of spinal cord injury

Autor: Shi Benchao, Yao Shun, Dong Chao, Mo Biling, Huang Shuai, Zhang Hui, Zhou Zhilai, Qiu Sujun
Rok vydání: 2016
Předmět:
0301 basic medicine
Cell Survival
Apoptosis
Mesenchymal Stem Cell Transplantation
Andrology
Random Allocation
03 medical and health sciences
Paracrine signalling
chemistry.chemical_compound
0302 clinical medicine
Neurotrophic factors
medicine
Animals
Humans
Molecular Biology
Spinal cord injury
Cells
Cultured
Spinal Cord Injuries
Cell Proliferation
business.industry
Macrophages
General Neuroscience
Mesenchymal stem cell
Mesenchymal Stem Cells
Recovery of Function
medicine.disease
Cell Hypoxia
Nerve Regeneration
Rats
Transplantation
Vascular endothelial growth factor
Disease Models
Animal
030104 developmental biology
chemistry
Immunology
Hepatocyte growth factor
Cord Blood Stem Cell Transplantation
Microglia
Neurology (clinical)
Stem cell
business
030217 neurology & neurosurgery
Developmental Biology
medicine.drug
Zdroj: Brain Research. 1642:426-435
ISSN: 0006-8993
DOI: 10.1016/j.brainres.2016.04.025
Popis: Human umbilical cord mesenchymal stem cells (UCMSCs) have recently been shown to hold great therapeutic potential for the treatment of spinal cord injury (SCI). However, the number of engrafted cells has been shown to decrease dramatically post-transplantation. Physioxia is known to enhance the paracrine properties and immune modulation of stem cells, a notion that has been applied in many clinical settings. We therefore hypothesized that preconditioning of UCMSCs in physioxic environment would enhance the regenerative properties of these cells in the treatment of rat SCI. UCMSCs were pretreated with either atmospheric normoxia (21% O2, N-UCMSC) or physioxia (5% O2, P-UCMSC). The MSCs were characterized using flow cytometry, immunocytochemistry, and real-time polymerase chain reaction. Furthermore, 10(5) N-UCMSC or P-UCMSC were injected into the injured spinal cord immediately after SCI, and locomotor function as well as cellular, molecular and pathological changes were compared between the groups. We found that N-UCMSC and P-UCMSC displayed similar surface protein expression. P-UCMSC grew faster, while physioxia up-regulated the expression of trophic and growth factors, including hepatocyte growth factor (HGF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor(VEGF), in UCMSCs. Compared to N-UCMSC, treatment with P-UCMSC was associated with marked changes in the SCI environment, with a significant increase in axonal preservation and a decrease in the number of caspase-3+ cells and ED-1+ macrophages. These changes were accompanied by improved functional recovery. Thus, the present study indicated that preculturing UCMSCs under 5% lowered oxygen physioxic conditions prior to transplantation improves their therapeutic potential for the treatment of SCI in rats.
Databáze: OpenAIRE
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