Transforming growth factor β–transduced mesenchymal stem cells ameliorate experimental autoimmune arthritis through reciprocal regulation of Treg/Th17 cells and osteoclastogenesis

Objective

Bone marrow–derived mesenchymal stem cells (MSCs) can prevent various autoimmune diseases. We examined the therapeutic potential of transforming growth factor β (TGFβ)–transduced MSCs in experimental autoimmune arthritis, using an accepted animal model of collagen‐induced arthritis (CIA).

Methods

DBA/1J mice with CIA were treated with syngeneic TGFβ‐induced MSCs, whereas control mice received either vehicle or MSCs alone. Arthritis severity was assessed by clinical and histologic scoring. TGFβ‐transduced MSCs were tested for their immunosuppressive ability and differential regulation in mice with CIA. T cell responses to type II collagen were evaluated by determining proliferative capacity and cytokine levels. The effects of TGFβ‐transduced MSCs on osteoclast formation were analyzed in vitro and in vivo.

Results

Systemic infusion of syngeneic TGFβ‐transduced MSCs prevented arthritis development and reduced bone erosion and cartilage destruction. Treatment with TGFβ‐transduced MSCs potently suppressed type II collagen–specific T cell proliferation and down‐regulated proinflammatory cytokine production. These therapeutic effects were associated with an increase in type II collagen–specific CD4+FoxP3+ Treg cells and inhibition of Th17 cell formation in the peritoneal cavity and spleen. Furthermore, TGFβ‐transduced MSCs inhibited osteoclast differentiation.

Conclusion

TGFβ‐transduced MSCs suppressed the development of autoimmune arthritis and joint inflammation. These data suggest that enhancing the immunomodulatory activity of MSCs and modulating T cell–mediated immunity using gene‐modified MSCs may be a gateway for new therapeutic approaches to clinical rheumatoid arthritis.

     

Association between onchocerciasis and epilepsy in the Itwara hyperendemic focus, West Uganda: controlling for time and intensity of exposure

In 38 pairs of epilepsy patients and controls matched for time and intensity of exposure to transmission of onchocerciasis, the presence of microfilariae in the skin of epilepsy patients was found insignificantly elevated compared with controls (odds ratio = 1.68; 95% confidence interval [CI] = 0.60-4.57; P = 0.31). This difference was more pronounced when detection of subcutaneous nodules was used as indication of infection with Onchocerca volvulus (odds ratio = 2.77; 95% CI = 0.92-8.33; P = 0.065). These findings from a patient group of limited size suggest that intensity of infection may play a substantial role in the development of onchocerciasis-associated epilepsy. Our results are in contrast to the results of two other independent studies from the identical endemic area; one case concluded a significant positive correlation between onchocerciasis and epilepsy, and the other case concluded a clearly negative correlation. Studies with a greater sample size are needed to confirm this possible relationship.     

The combined effect of granulocyte-colony stimulating factor (G-CSF) treatment and exercise in rats with spinal cord injury

Objective: To identify that the combined G-CSF and treadmill exercise is more effective in functional recovery after spinal cord injury (SCI).

Design: Rats were divided into 4 groups: a SCI group treated with G-CSF (G-CSF group, n?=?6), a SCI group treated with treadmill exercise plus G-CSF (G-CSF/exercise group, n?=?6), a SCI group with treadmill exercise (exercise group, n?=?6), and a SCI group without treatments (control group, n?=?6). We performed laminectomy at the T8–10 spinal levels with compression injury of the spinal cord in all rats. G-CSF (20?μg/ml) was administered intraperitoneally for 5 consecutive days after SCI in G-CSF and G-CSF/exercise groups. From one week after surgery, animals in G-CSF/exercise and exercise groups received 30?min of exercise 5 days per week for 4 weeks. Functional recoveries were assessed using the Basso, Beattie, and Bresnahan (BBB) scale and the inclined plane test. Five weeks after SCI, hematoxylin and eosin staining for cavity size and immunohistochemistry for glial scar formation and neuro-regeneration factor expression were conducted.

Setting: Inha University School of medicine, Incheon, Korea

Results: Rats in G-CSF/exercise group showed the most effective functional recovery in the BBB scale and the inclined plane test, and spinal cord cavity size by injury were the smallest, and immunohistochemistry revealed expression of higher BDNF (brain-derived neurotrophic factor) and VEGF (vascular endothelial growth factor) and lower GFAP (glial fibrillary acidic protein) than others.

Conclusion: Combined treatment provided more effective neuroplasty and functional recovery than individual treatments.     

Evaluation of Current Resources Available for Community-Based Cardiac Rehabilitation in Korea: A Nationwide Survey Study

BackgroundIn Korea, the actual distribution of cardiac rehabilitation (CR) to the clinical field is insufficient due to the many barriers for cardiovascular patients to participate in CR. Community-based CR is a useful alternative to overcome these obstacles. Through a nationwide survey, we investigated the possibility of regional medical and public health management institutes which can be in charge of community-based CR in Korea.MethodsThe questionnaires on recognition of CR and current available resources in health-related institutions were developed with reference to the CR evaluation tools of York University and the International Council of Cardiovascular Prevention and Rehabilitation. The questionnaires were sent to regional public and private medical institutions and public health management institutions.ResultsIn total, 2,267 questionnaires were sent to 1,186 institutions. There were 241 and 242 responses from 173 and 179 regional private and public medical institutions, respectively. And a total of 244 responses were gathered from 180 public health management institutions. Although many institutions were equipped with the necessary facilities for exercise training, there were few patient-monitoring systems during exercise. Most institutions were aware of the need for CR, but were burdened with the cost of establishing personnel and facilities to operate CR.ConclusionMost regional medical, and public health management institutions in Korea are unprepared for the implementation of community-based CR programs. To encourage the utilization of such, there should be efforts to establish a national consensus.