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Osteoarthritis (OA) is degenerative disease, leading to pain and functional disability. It is reported that polydeoxyribonucleotide (PDRN) is a suitable therapy for OA. However, the therapeutic mechanisms of PDRN in OA are not fully understood. To investigate the effect of PDRN in an in vitro model of OA, interleukin (IL)-1β or phosphate-buffered saline (PBS) was used to treat a human chondrocytic cell line in hypoxic conditions for 24 h (IL-1β group or control group). PDRN was then used to treat IL-1β group cells for 24 h (PDRN group). By Label-Based Human Antibody Array 1000, angiopoietin-2 (ANG-2), platelet-derived growth factor (PDGF), angiostatin, and endostatin, which were related to angiogenesis, were chosen for further validation studies. Quantitative real-time reverse transcription polymerase chain reaction and western blot analysis validated that the levels of PDGF and ANG-2, which were related to pro-angiogenesis, were significantly increased in the PDRN group compared with those in the control group or the IL-1β group. However, the levels of endostatin and angiostatin, which were related in anti-angiogenesis, were significantly decreased in the PDRN group compared with those in the control group or the IL-1β group. In the same manner, vascular endothelial growth factor, which was a mediator of angiogenesis, was significantly increased in the PDRN group compared with those in the control group or the IL-1β group. Furthermore, wound closure was significantly increased in the PDRN group compared with the control group or the IL-1β group by in vitro scratch assay. Moreover, PDRN decreased expression of metalloproteinase 13, as a catabolic factor for OA, but increased expression of aggrecan, which was an anabolic factor for OA. These data suggest that PDRN may promote angiogenesis and wound healing via down-regulation of catabolism and up-regulation of anabolism in an in vitro model of OA.

Spinal cord injury (SCI) is a devastating neurological disease. The pathophysiological mechanisms of SCI have been reported to be relevant to central nervous system injury such as brain injury. In this study, gene expression of the brain after SCI was elucidated using transcriptome analysis to characterize the temporal changes in global gene expression patterns in a SCI mouse model. Subjects were randomly classified into 3 groups: sham control, acute (3 h post-injury), and subacute (2 wk post-injury) groups. We sought to confirm the genes differentially expressed between post-injured groups and sham control group. Therefore, we performed transcriptome analysis to investigate the enriched pathways associated with pathophysiology of the brain after SCI using Database for Annotation Visualization, and Integrated Discovery (DAVID), which yielded Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Following enriched pathways were found in the brain: oxidative phosphorylation pathway; inflammatory response pathways—cytokine–cytokine receptor interaction and chemokine signaling pathway; and endoplasmic reticulum (ER) stress-related pathways—antigen processing and presentation and mitogen-activated protein kinase signaling pathway. Oxidative phosphorylation pathway was identified at acute phase, while inflammation response and ER stress-related pathways were identified at subacute phase. Since the following pathways—oxidative phosphorylation pathway, inflammatory response pathways, and ER stress-related pathways—have been well known in the SCI, we suggested a link between SCI and brain injury. These mechanisms provide valuable reference data for better understanding pathophysiological processes in the brain after SCI.

This study was designed to investigate functional recovery after the transplantation of mesenchymal stem cells (MSCs) or neurally differentiated MSCs (NMSCs) derived from bone marrow in a rat model of spinal cord injury (SCI). Sprague-Dawley rats were subjected to incomplete SCI using an NYU impactor to create a free drop contusion at the T9 level. The SCI rats were then classified into three groups; MSCs, NMSCs, and phosphate-buffered saline (PBS)-treated groups. The cells or PBS were administrated 1 week after SCI. Basso-Beattie-Bresnahan (BBB) locomotor rating scores were measured at 1-week intervals for 9 weeks. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were also recorded 8 weeks after transplantation. While transplantation of MSCs led to a clear tendency of motor recovery, NMSC-treated rats had significantly improved BBB scores and showed significantly shortened initial latency, N1 latency, and P1 latency of the SSEPs compared to PBS controls. In addition, 5-bromo-2-deoxyuridine (BrdU)-prelabeled MSCs costained for BrdU and glial fibrillary acidic protein (GFAP) or myelin basic protein (MBP) were found rostrally and caudally 5 mm each from the epicenter of the necrotic cavity 4 weeks after transplantation. These results suggest that neurally differentiated cells might be an effective therapeutic source for functional recovery after SCI.

Neural stem cells (NSCs) persist in the subventricular zone lining the ventricles of the adult brain. The resident stem/progenitor cells can be stimulated in vivo by neurotrophic factors, hematopoietic growth factors, magnetic stimulation, and/or physical exercise. In both animals and humans, the differentiation and survival of neurons arising from the subventricular zone may also be regulated by the trophic factors. Since stem/progenitor cells present in the adult brain and the production of new neurons occurs at specific sites, there is a possibility for the treatment of incurable neurological diseases. It might be feasible to induce neurogenesis, which would be particularly efficacious in the treatment of striatal neurodegenerative conditions such as Huntington's disease, as well as cerebrovascular diseases such as ischemic stroke and cerebral palsy, conditions that are widely seen in the clinics. Understanding of the molecular control of endogenous NSC activation and progenitor cell mobilization will likely provide many new opportunities as therapeutic strategies. In this review, we focus on endogenous stem/progenitor cell activation that occurs in response to exogenous factors including neurotrophic factors, hematopoietic growth factors, magnetic stimulation, and an enriched environment. Taken together, these findings suggest the possibility that functional brain repair through induced neurorestoration from endogenous stem cells may soon be a clinical reality.

We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE ( n = 18), ASC-SC ( n = 19), PBS-EE ( n = 12), PBS-SC ( n = 17), and untreated controls ( n = 23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin+ neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU+βIII-tubulin+ neurons, GFAP+ astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56+ glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.