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Seongnam, South Korea

Jang Y.O.,Yonsei University | Kim Y.J.,Yonsei University | Baik S.K.,Yonsei University | Kim M.Y.,Yonsei University | And 10 more authors.
Liver International | Year: 2014

Background: In experimental models, bone marrow-derived mesenchymal stem cells (BM-MSCs) have the capacity to differentiate into hepatocytes and exhibit antifibrotic effects. However, there have been no studies in humans with alcoholic cirrhosis. Aim: The aim of this study was to elucidate the antifibrotic effect of BM-MSCs in patients with alcoholic cirrhosis, as a phase II clinical trial. Methods: Twelve patients (11 males, 1 female) with baseline biopsy-proven alcoholic cirrhosis who had been alcohol free for at least 6 months were enrolled. BM-MSCs were isolated from each patient's BM and amplified for 1 month, and 5 × 107 cells were then injected twice, at weeks 4 and 8, through the hepatic artery. One patient was withdrawn because of ingestion of alcohol. Finally, 11 patients completed the follow-up biopsy and laboratory tests at 12 weeks after the second injection. The primary outcome was improvement in the patients' histological features. Results: According to the Laennec fibrosis system, histological improvement was observed in 6 of 11 patients (54.5%). The Child-Pugh score improved in ten patients (90.9%) and the levels of transforming growth factor-β1, type 1 collagen and α-smooth muscle actin significantly decreased (as assessed by real-time reverse transcriptase polymerase chain reaction) after BM-MSCs therapy (P < 0.05). No significant complications or side effects were observed during this study. Conclusions: Bone marrow-derived mesenchymal stem cells therapy in alcoholic cirrhosis induces a histological and quantitative improvement of hepatic fibrosis. © 2013 John Wiley & Sons A/S. Source

Bae K.S.,Yonsei University | Park J.B.,Yonsei University | Kim H.S.,Yonsei University | Kim H.S.,FCB Pharmicell Co. | And 3 more authors.
Yonsei Medical Journal | Year: 2011

Purpose: Mesenchymal stem cells (MSCs) are multipotent and give rise to distinctly differentiated cells from all three germ layers. Neuronal differentiation of MSC has great potential for cellular therapy. We examined whether the cluster of mechanically made, not neurosphere, could be differentiated into neuron-like cells by growth factors, such as epidermal growth factor (EGF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF). Materials and Methods: BMSCs grown confluent were mechanically separated with cell scrapers and masses of separated cells were cultured to form cluster BMSCs. As described here cluster of BMSCs were differentiated into neuron-like cells by EGF, HGF, and VEGF. Differentiated cells were analyzed by means of phase-contrast inverted microscopy, reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence, and immunocytochemistry to identify the expression of neural specific markers. Results: For the group with growth factors, the shapes of neuron-like cells was observable a week later, and two weeks later, most cells were similar in shape to neuron-like cells. Particularly, in the group with chemical addition, various shapes of filament structures were seen among the cells. These culture conditions induced MSCs to exhibit a neural cell phenotype, expressing several neuro-glial specific markers. Conclusion: bone marrow-derived mesenchymal stem cells (BMSCs) could be easily induced to form clusters using mechanical scraping, not neurospheres, which in turn could differentiate further into neuron-like cells and might open an attractive possibility for clinical cell therapy for neurodegenerative diseases. In the future, we consider that neuron-like cells differentiated from clusters of BMSCs are needed to be compared and analyzed on a physiological and molecular biological level with preexisting neuronal cells, and studies on the possibility of their transplantation and differentiation capability in animal models are further required. © Yonsei University College of Medicine 2011. Source

Kim J.-H.,Yonsei University | Jung M.,Yonsei University | Kim H.-S.,Yonsei University | Kim Y.-M.,FCB Pharmicell Co. | Choi E.-H.,Yonsei University
Experimental Dermatology | Year: 2011

Stem cells are undifferentiated cells, which have the important properties of self-renewal and differentiation. Adipose-derived stem cells (ADSC) have relative advantages in accessibility and abundance compared to other kinds of stem cells. Regeneration therapy using ADSC has received attention in the treatment of various dermatologic diseases. In previous studies, ADSC were shown to have antioxidant, whitening and wound-healing effects in the skin through secretion of growth factors and by activating fibroblasts. In this study, we investigated whether ADSC could be used as an anti-ageing therapy, especially by dermal collagen synthesis and angiogenesis. Subcutaneous injection of ADSC significantly increased collagen synthesis in hairless mice, and dermal thickness, collagen density and fibroblast number also increased. In addition, procollagen type I protein and mRNA expression increased, which accounts for the increased dermal collagen density. Angiogenesis, which was visualized by CD31 and NG2 immunofluorescence stains, also increased in ADSC-treated skin. Our results suggest that ADSC therapy may be useful in ageing skin. Its effects are mainly mediated by stimulating collagen synthesis in dermal fibroblasts and increasing angiogenesis. © 2011 John Wiley & Sons A/S. Source

Kang K.N.,Ajou University | Kim D.Y.,Ajou University | Yoon S.M.,Ajou University | Lee J.Y.,Ajou University | And 11 more authors.
Biomaterials | Year: 2012

The present study employed a combinatorial strategy using poly(d,l-lactide-co-glycolide) (PLGA) scaffolds seeded with human mesenchymal stem cells (hMSCs) to promote cell survival, differentiation, and neurological function in a completely transected spinal cord injury (SCI) model. The SCI model was prepared by complete removal of a 2-mm length of spinal cord in the eighth-to-ninth spinal vertebra, a procedure that resulted in bilateral hindlimb paralysis. PLGA scaffolds 2 mm in length without hMSCs (control) or with different numbers of hMSCs (1 × 10 5, 2 × 10 4, and 4 × 10 3) were fitted into the completely transected spinal cord. Rats implanted with hMSCs received Basso-Beattie-Bresnahan scores for hindlimb locomotion of about 5, compared with ~2 for animals in the control group. The amplitude of motor-evoked potentials (MEPs) averaged 200-300 μV in all hMSC-implanted SCR model rats. In contrast, the amplitude of MEPs in control group animals averaged 135 μV at 4 weeks and then declined to 100 μV at 8 weeks. These results demonstrate functional recovery in a completely transected SCI model under conditions that exclude self-recovery. hMSCs were detected at the implanted site 4 and 8 weeks after transplantation, indicating in vivo survival of implanted hMSCs. Immunohistochemical staining revealed differentiation of implanted hMSCs into nerve cells, and immunostained images showed clear evidence for axonal regeneration only in hMSC-seeded PLGA scaffolds. Collectively, our results indicate that hMSC-seeded PLGA scaffolds induced nerve regeneration in a completely transected SCI model, a finding that should have significant implications for the feasibility of therapeutic and clinical hMSC-delivery using three-dimensional scaffolds, especially in the context of complete spinal cord transection. © 2012 Elsevier Ltd. Source

Lee J.S.,Yonsei University | Song D.-Y.,Eulji University | Cho W.G.,Yonsei University | Lee J.Y.,Yonsei University | And 5 more authors.
Molecular and Cellular Toxicology | Year: 2015

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the elderly, and therefore, the demand for effective therapies against PD has greatly increased. Therapeutic applications of stem cells have been considered to be one of the promising approaches in PD therapy. In the present study, the neuroprotective effects of hMSCs were evaluated in a parkinsonian rat model. The animal model was established by injecting 6-hydroxydopamine into the striatum of rats. Two weeks later, cultured hMSCs were transplanted into the cisterna magna. We subsequently identified changes in the expression of inflammatory cytokines, neurotrophic factors, microglial activation, and the survival rate of dopaminergic neurons in SNc. Behavioral recovery was also examined. The results indicated that hMSC transplantation increased the expression of anti-inflammatory cytokines as well as neurotrophic factors, and decreased the number of activated microglia. Compared to the sham-grafted group, relatively large numbers of TH-positive neurons were found in the ipsilateral SNc, and amphetamine-induced asymmetrical rotation was significantly reduced after hMSC transplantation. These findings suggest that hMSCs might be neuroprotective, probably through up-regulation of neurotrophic factors and anti-inflammatory cytokines, and this could have a functional impact in reversing PD symptoms. © 2015, The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht. Source

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