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Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7
<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>
Bhang, Suk Ho,Lee, Seahyoung,Shin, Jung-Youn,Lee, Tae-Jin,Jang, Hyeon-Ki,Kim, Byung-Soo Elsevier 2014 MOLECULAR THERAPY Vol.22 No.4
<P>Using stem cell-conditioned medium (CM) might be a viable alternative to stem cell transplantation, which is often hampered by low grafting efficiency and potential tumorigenesis, but the concentrations of angiogenic growth factors in CM are too low for therapeutic use and some components of the medium are not for human use. We used three-dimensional (3D) spheroid culture of human adipose-derived stem cells (ADSCs) with clinically relevant medium composed of amino acids, vitamins, glucose, and human serum to produce clinically relevant CM containing angiogenic and/or antiapoptotic factors such as vascular endothelial cell growth factor, fibroblast growth factor 2, hepatocyte growth factor, and chemokine (C-X-C motif) ligand 12. The concentrations of these factors were 23- to 27-fold higher than that in CM produced by conventional monolayer culture. Compared with injection of either monolayer culture CM or human ADSC, injection of spheroid culture CM to an ischemic region in mice significantly enhanced endothelial cell growth, CD34(+)/PTPRC(-) (endothelial progenitor) cell mobilization from bone marrow, and bone marrow cell homing to the ischemic region, resulting in improved blood vessel density, limb salvage, and blood perfusion in a mouse hindlimb ischemia model. The stem cell CM developed in this study will likely be an effective alternative to conventional stem cell transplantation therapy.</P>
Bhang, Suk Ho,Jeon, Jeong-Yi,La, Wan-Geun,Seong, Jun Yeup,Hwang, Jin Wook,Ryu, Seong Eon,Kim, Byung-Soo Published for the International Union of Biochemis 2011 Biotechnology and Applied Biochemistry Vol.58 No.4
<P>This study was designed to evaluate the additive effects of transforming growth factor-beta3 (TGF-β3) and hyaluronic acid (HA) on chondrogenic differentiation of human mesenchymal stem cells (hMSCs). The hMSCs were cultured on collagen type I-, HA-, or fibronectin-coated cell culture dishes with or without TGF-β3 added to the culture medium. Four weeks after cell culture, chondrogenic differentiation of hMSCs was determined by evaluating the expression of cartilage-specific markers using real-time polymerase chain reaction, immunocytochemistry, and Western blot analysis. hMSCs cultured on HA-coated dishes with TGF-β3 supplementation revealed a prominent increase in collagen type II, aggrecan, and Sox9. When hMSCs were cultured without TGF-β3 supplementation, only hMSCs cultured on HA-coated dishes showed prominent expression of the cartilage-specific markers. This study shows that chondrogenic differentiation of hMSCs can be enhanced additively by interactions with both a specific cell-adhesion matrix and a soluble growth factor.</P>
Bhang, Suk Ho,Park, Jooyeon,Yang, Hee Seok,Shin, Jaehoon,Kim, Byung-Soo SAGE Publications 2013 CELL TRANSPLANTATION Vol.22 No.3
<P>The administration of human adipose-derived stromal cells (hASCs) enhances skin wound healing. However, poor survival of hASCs that are administered to avascular wound regions may limit the therapeutic efficacy of the hASCs. The aim of this study was to determine whether the coadministration of platelet-rich plasma (PRP) and hASCs enhanced the skin wound-healing efficacy of hASCs. Skin regeneration was examined in skin wounds of athymic mice that were either untreated or treated with hASCs, PRP, or both hASCs and PRP. Coadministration of PRP and hASCs resulted in better skin regeneration than hASC administration alone in part by significantly improving the proliferation of administered hASCs by the angiogenic growth factor secretion of the hASCs and surrounding mouse host cells in the wound areas and by promoting neovascularization in the wound beds.</P>
Bhang, Suk Ho,Lee, Tae-Jin,La, Wan-Geun,Kim, Dong-Ik,Kim, Byung-Soo Elsevier 2011 Journal of bioscience and bioengineering Vol.111 No.5
<P><B>Abstract</B></P><P>Transplantation of cord blood-derived mesenchymal stem cells (CBMSCs) into ischemic regions could be a potential therapy for the treatment of ischemic disease, but its efficacy is limited by poor cell survival. We hypothesized that local delivery of fibroblast growth factor 2 (FGF2) to the site of CBMSC transplantation would enhance the viability of CBMSCs transplanted to ischemic tissues. Human CBMSCs were loaded onto fibrin gel with or without FGF2 and transplanted intramuscularly into either normal or ischemic hindlimbs of athymic mice. CBMSC transplantation combined with FGF2 delivery resulted in significantly lower apoptosis and higher survival of transplanted CBMSCs. The enhanced cell survival could be due to the local delivery of FGF2 and the enhanced secretion of anti-apoptotic factor. CBMSC transplantation and FGF2 delivery enhanced the expression of host-derived, platelet-derived growth factor-β and NG2, which induce endothelial cell homing and pericyte recruitment, respectively, and more effectively protected muscles from ischemic degeneration when compared to CBMSC transplantation alone. FGF2 delivery to the site of CBMSC transplantation can enhance the survival of CBMSCs transplanted into ischemic tissues. This approach could be used to improve the angiogenic efficacy of CBMSC transplantation therapy for ischemic disease.</P>
Bhang, Suk Ho,Cho, Seung-Woo,Lim, Jae Min,Kang, Jin Muk,Lee, Tae-Jin,Yang, Hee Seok,Song, Young Soo,Park, Moon Hyang,Kim, Hyo-Soo,Yoo, Kyung-Jong,Jang, Yangsoo,Langer, Robert,Anderson, Daniel G.,Kim, Wiley (John WileySons) 2009 Stem Cells Vol.27 No.8
<P>Ischemia is a potentially fatal medical event that is associated with as many as 30% of all deaths. Stem cell therapy offers significant therapeutic promise, but poor survival following transplantation to ischemic tissue limits its efficacy. Here we demonstrate that nanosphere-mediated growth factor delivery can enhance the survival of transplanted human adipose-derived stromal cells (hADSCs) and secretion of human angiogenic growth factors per cell, and substantially improve therapeutic efficacy of hADSCs. In vitro, in hypoxic (1% oxygen) and serum-deprived conditions that simulate in vivo ischemia, fibroblast growth factor-2 (FGF2) significantly reduced hADSC apoptosis and enhanced angiogenic growth factor secretion. In vivo, hADSCs delivered intramuscularly into ischemic hind limbs in combination with FGF2 resulted in significant improvements in limb survival and blood perfusion, as well as survival of the transplanted hADSCs and secretion of human angiogenic growth factors (i.e., vascular endothelial growth factor, hepatocyte growth factor, and FGF2). Interestingly, the majority of transplanted hADSCs were localized adjacent to the microvessels rather than being incorporated into them, suggesting that their major contribution to angiogenesis might be to increase paracrine secretion of angiogenic growth factors. This study demonstrates the potential of hADSCs in combination with growth factors for use in the treatment of ischemia.</P>
The behavior of neural stem cells on biodegradable synthetic polymers
Bhang, Suk Ho,Lim, Jung Su,Choi, Cha Yong,Kwon, Yunhee Kim,Kim, Byung-Soo Informa UK (TaylorFrancis) 2007 Journal of Biomaterials Science. Polymer Edition Vol.18 No.2
<P>The biocompatibility of polymer scaffolds as neural stem cell transplantation matrices has not yet been studied extensively. In this study, we evaluated the biocompatibility of various biodegradable polymers for neural stem cells. The biocompatibility tests were performed by culturing hippocampal progenitor cells (HiB5) on films of poly(lactic-co-glycolic acid) (PLGA), poly(L-lactide-co-epsilon-caprolactone) (PLCL) and poly(L-lactic acid) (PLLA) or in the presence of extracts from these polymers. Specifically, the viability, mitochondrial metabolic activity, proliferation, apoptosis and neurite out-growth of HiB5 cells were examined in biocompatibility tests. Among the tested polymers, PLGA performed best with respect to cell viability, mitochondrial metabolic activity and apoptotic activity. Compared to the other polymers, PLLA showed the worst results in all categories evaluated. PLGA also showed favorable results for neurite out-growth of HiB5 cells. The results of this study demonstrate the promising biocompatibility of PLGA as a scaffold for neural stem cell transplantation for nerve regeneration.</P>