Speaker : Seung Jin Lee Ph.D. Dept. of Pharmacy, Ewha Womans University, Seoul, Korea 

Date : 2012-10-17

Location : Room 106Pharmacy Hall, Dankook University

Abstract : Diseases that cause impaired human organs and tissues have increased due to an expanded life span, natural disasters, and other illnesses.  The essential factors in regenerative therapy include cells, scaffolds and delivery technology of bioactive agents.  Stem cells have been in extremely high demands for tissue regeneration; however, they are somewhat limited in functionality over passages, differentiation potential and sufficient sourcing. 

Stem cell engineering through gene delivery may be possible to enhance its functionality and regeneration capacity. Gene delivery has been beset by low transfection efficiency of inserted gene and poor retention at the applied site.  Alternative non-viral gene delivery technology has thus been pursued for promoted transfection efficiency. Further controlled release from biodegradable scaffolds may overcome the limited longevity of transfected genes during the course of regeneration process. 

CPP could be successfully employed as DNA carrier to stem cells in a form of stable pDNA-CPP complex and markedly increased the transfection efficiency over the existing vectors such as polyplexes and lipoplexes. Controlled gene delivery from fibrous 3-D scaffolds loaded with pDNA/CPP nano-complexes significantly enhanced gene-transfection in a prolonged manner to maximize the regeneration potential. Stem cells are truly promising for regenerative therapy; however, their critical issues still remain in unsettled cell source/outcomes, purity assurance and functionality guarantee. Beyond the general mesenchymal stem cells, i.e., BMSC, UCMSC, ASC, significance of resident stem cells was proved for its profound regeneration function, as strongly supported by innovative isolation process. Novel cell delivery technology was requisite to acquire successful regeneration score. Construction of the stem cells with special target-oriented scaffolds provided key for the treatment of intractable diseases.  These approaches may be highly promising to upgrade the status of tissue regenerative therapy.  In addition, the novel stem cell delivery technology will provide breakthrough and unmet needs for the treatment of intractable diseases.

Speaker : Gun-Il Im, Ph.D. (Dept of Orthopaedics, Dongguk University Ilsan Hospital) 

Date : 2012-10-26

Location : Room 106Pharmacy Hall, Dankook University

Abstract : Adult stem cells have drawn attention as an attractive cell source for tissue regeneration. Mesenchymal stem cells (MSCs) in adults are capable of self-regeneration and differentiation into several cell types. While bone marrow provides the most universal source of MSCs, other tissues such as the periosteum, muscle, synovial membrane and adipose tissue also possess MSCs. Of these, adipose tissue offers a unique source of stem cells with considerable advantages for its accessibility and abundance. The adipose stem cells (ASCs) obtained from lipoaspirates have been also proven to possess the multilineage potential.

The focus of musculoskeletal tissue engineering is the regeneration of bone and cartilage. 

To achieve the goal, an effective induction of differentiation poses a key challenge in the use of adult stem cells. While osteogenic differentiation of bone marrow MSCs is easily induced, ASCs have much lower osteogenic potentials than bone marrow MSCs. It can be enhanced with the used of vitamin D or BMPs. Gene transfer of osteogenic growth factors such as BMPs or transcription factors such as Runx-2 and Osterix can markedly enhance the osteogenic potential of ASCs. Recent advancement in nonviral gene transfer by electroporation has achieved a high transfection rate, and shed a light to their possible clinical application. Chondrogenic differentiation of MSCs poses greater challenge than osteogenic differentiation. TGF- has been used to induce chondrogenesis from MSCs, but the markers of hypertrophy increase along with chondrogenic markers in this setting. Inhibitor of hypertrophy such as PTHrP can be used to induce chondrogenesis while suppressing hypertrophy from MSCs. It is even difficult to induce chondrogenesis from ASCs, requiring greater doses or different combination of growth factors. The nonviral gene transfer of SOX trio, the key transcription factors of chondrogenic differentiation, can also enhance the chondrogenesis from MSCs and ASCs. 

In conclusion, great efforts have been devoted to the research to engineer bone or cartilage from adult stem cells and various strategies for tissue engineering from stem cells have been developed. Nevertheless, a lot of unsolved questions and dilemmas remain until we obtain tissues of high quality from stem cells. 

Speaker : Hyuk Sang Yoo, Ph.D. (Department of Biomaterials Engineering, College of Biomedical Science Kangwon National University)

Date : 2012-10-31

Location : Room 107Pharmacy Hall, Dankook University


Abstract : Biomedical applications of electrospun nanofibrous meshes have been receive tremendous attentions because of their unique structures and versatilities as novel biomaterials. Incorporation of growth factors in fibrous meshes can be performed by surface-modification and encapsulation. Those growth factors stimulate differentiation and proliferation of specific types of cells and thus lead tissue regenerations of specific cell types. Topographical cues of electrospun nanofibrous meshes also increase differentiation of specific cell types according to alignments of fibrous structures. Wound healing treatments of diabetic ulcers were performed using nanofibrous meshes encapsulating multiple growth factors. Aligned nanofibrous meshes and those with random configuration were compared for differentiating mesenchymal stem cells into neuronal cells. Thus, nanofibrous meshes can be applied to novel drug delivery carriers and matrix for promoting cellular proliferation.

Speaker : Jin Ho Lee, Ph.D. (Department of Advanced Materials, Hannam University)

Date : 2012-11-30

Location : Room 106Pharmacy Hall, Dankook University

Abstract : In recent years, various biocompatible polymers have been utilized to fabricate porous scaffolds or injectable carriers for cell culture or regenerate tissue-based artificial organs. In this presentation, various types of polymeric biomaterials for biomedical and tissue engineering applications carried out in our laboratory will be discussed. They include 3-D cell scaffolds for cartilage or bone regeneration, 2-D asymmetric porous membrane or tube for guided bone, tendon or nerve regeneration, and injectable porous beads and hydrogel systems as a tissue adhesion barrier or bulking agent for urinary/fecal incontinence treatment.

Thursday, 30 July 2015 10:10

40 - Collagen Matrix

Speaker : 양은경 (주)바이오랜드 의과학연구소 부소장

Date : 2012-12-07

Location : Room 106Pharmacy Hall, Dankook University

Abstract : 조직공학 생체재료로서 개발된 수많은 우수한 재료 중 하나인 collagen matrix의 산업화를 위해서는 주변기술의 발전으로 생체재료기술, 조직공학기술, 생체재료의 안전성 유효성 평가기술 등과 같은 기술인프라의 발전 또한 선행되어야하는데, 우리나라 관련분야의 연구개발자와 산업체의 활성화로 국내 연구역량은 성숙단계에 들었다고 할 수 있다. 다만, 생체재료의 특성 상 위협요인으로 상품화에 장기간이 소요되며, 동물 비임상 시험을 통한 안전성 및 유효성 평가, 임상시험 승인절차 및 임상시험 등 여러단계를 거쳐야하므로 장기간의 시간과 고비용의 투자가 필요한 산업이다. 산학연 협동을 통한 연구개발 결과물과 산업체의 투자와 노력으로 제품이 개발되고 허가를 받은 후에도 시장의 변화, 정부의 가격 정책, 보험 정책, 해외진출 노력과 지원 등을 통하여 조직공학 생체재료 산업은 더욱 성장할 수 있을 것이다.

Friday, 31 July 2015 10:10

41 - Laryngeal Regenerative Medicine

Speaker : Jae-Yol Lim, MD, PhD (Dept. of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine)

Date :2013-01-0

Location : Room 106,Pharmacy Hall, Dankook University

Abstract : Laryngeal tissue engineering has emerged in the last decade, although clinical applications are rare. Research on laryngeal tissue engineering includes vocal fold (VF) regeneration for prevention or treatment of vocal fold scar, VF scaffolding surgery (augmentation laryngoplasty) for treatment of glottal insufficiency, laryngeal nerve regeneration for functional restoration of vocal cord paralysis, and laryngeal cartilage regeneration for laryngeal framework reconstruction. 

VF scar is one of the most common intractable dysphonia caused by vocal abuse, surgery, or inflammation and still remains therapeutic challenge. Therapeutic strategies based on the principles of tissue engineering are receiving increasing attention in order to prevent or reverse VF scar. These strategies include not only cell therapy using stem/progenitor cells or VF fibroblasts, but also the development of scaffolds such as hyaluronic acid (HA) hydrogel and xenogeneic ECM or the delivery of soluble bioactive molecules such as growth factors and cytokines. Here I address the current status of research on VF regeneration based on review from recent in vivo and in vitro studies, and our experiments. 

Vocal cord paralysis by recurrent laryngeal nerve (RLN) damage is another cause of severe dysphonia and commonly results in serious complications such as communication impairment, aspiration, and dysphagia. However, reconstruction of RLN remains surgical challenge. For the treatment of vocal cord paralysis, VF scaffolding surgery such as injection laryngoplasty using a variety of biomaterials are in clinical use. Recently, biodegradable nerve guide conduits (NGC) have been successfully found to reconstruct the nerve defect. 

The aim of this lecture was to give a comprehensive overview about current knowledge in the field of laryngeal tissue engineering and regenerative medicine and furthermore to elucidate further trends in this fascinating field.

Speaker : Seong Keun Kwon, M.D., PhD. (Department of Otorhinolaryngology - Head and Neck Surgery, Dongguk University International  Hospital)

Date : 2013-01-04

Location : Room 106 Pharmacy Hall, Dankook University

Abstract : Disorders affecting the trachea may be curable by surgical resection of the affected segment and a subsequent end-to-end anastomosis. However, this standard approach is possible only when the diseased portion of the airway does not exceed approximately half (6 cm) of the total length of the trachea in an adult or one-third of the total length in a child. 

A conventional allotransplantation of a clinically relevant tracheal segment (>6 cm) is surgically challenging and requires lifelong immunosuppression. Almost all the early clinical efforts documented have resulted in allograft necrosis, infection, and death in patients due to inadequate graft revascularization, contact with inhaled air, and infection and mediastinitis.   

Autologous autografts have been clinically applied for small defects in the airway; however, for large disorders of the trachea, the optimal solution remains elusive. Cadaveric allografts have been used mainly for tracheal reconstruction in children, but the technical feasibility is overshadowed by a high rate of major complications and uncertainty regarding the long term. 

Artificial prostheses have also been used to replace the trachea, but this has always been associated with material migration, rupture, infection, stenosis, nonepithelialized endoluminal surface and related contamination, and consequent disintegration. 

In current general clinical practice, the use of artificial grafts is limited to temporary or palliative approaches using endoluminal stents or definitive tracheotomy. New therapeutic options are therefore necessary; however, even after decades of intensive research in this field, an optimal solution is still lacking.

The selection of the most reasonable scaffold is highly important for a suitable engineering process and subsequent in situ tissue/organ function. For instance, for replacing the trachea, a scaffold should meet with basic tracheal  characteristics such as being bioactive, capable of hosting the seeded cells, nonimmunogenic, nontoxic, and noncarcinogenic/nonteratogenic. In addition, an optimal tracheal scaffold is characterized by air- and liquid tight seals as well as adequate structural support (lateral rigidity and longitudinal flexibility) to maintain airway patency and allow rapid epithelialization. 

The cell type used for seeding the scaffold may be autologous or allogenic and can range from differentiated to stem or progenitor origin. Consideration needs to be given to the specific advantages and disadvantages of each cell type, and ethical concerns must be discussed. Moreover, the cell seeding and culture processes require tissue-specific conditions to mimic the physiologic environment. Conventional static dish culture conditions usually cannot provide these requirements, and the utilization of cell sheet technology or a bioreactor is necessary. 

Sunday, 02 August 2015 10:10

43 - Theragnosis for Cancer Treatment

Speaker : Kwangmeyung Kim, Ph.D (Biomedical Research Institute, Korea Institute of Science and Technology)

Date : 2013-01-14

Location : Room 106 Pharmacy Hall, Dankook University

Abstract : The new paradigm establishes polymeric nanoparticle-based theragnosis as a new method for molecular imaging, early diagnosis, and drug delivery system. With the help of polymer chemistry, we propose two different novel strategies using polymeric nanoparticles for the development of smart probes and new drug carriers for the treatment and imaging various diseases. First, we propose a new drug delivery system for cancer theragnosis based on the nanoparticle-based technology. Nano-sized drug delivery system, such as liposome, micelles, nanoparticles, have been intensively investigated for their use in tumor therapy. The effectiveness of drug delivery system can be attributed to their small size, reduced drug toxicity, controlled drug release and modification of drug pharmacokinetics and biodistribution. However, to date, only limited information is available on the interaction of nanoparticles and tumors mainly due to the limited availability of proper tools of real-time and non-invasive imaging of nano-sized drug carriers in the body. Our new optical imagining system allowed real-time and non-invasive evaluation of nanoparticles’ biodistribution in vivo and revealed that nanoparticles were only localized in tumor site. Furthermore the efficacy of nano-sized drug carriers can be optimized and quantified in vivo using the systems. Thus, we anticipate that polymeric nanoparticles could serve as potential candidate as selective drug carriers for specified tumors in vivo. 

Second, self-assembled and near-infrared fluorescence auto-quenched nanoparticular probes have been designed to visualize target molecules, such as proteases and protein kinases, in cellular levels. These nanoparticles should prove useful in cell-based high-throughput screens for chemicals that trigger apoptosis or protein kinases. It might also be possible to use these nanoparticles for detecting target molecules in live animals, perhaps even humans. Near-infrared radiation is not absorbed by the body, and thus, can be detected either through the skin or using fiber optic fluorescence detectors. 

Speaker : Hee Seok Yang, Ph.D. (Department of Bioengineering Center for Cardiovascular Biology Institute of Stem Cell and Regenerative Medicine University of Washington) 

Date : 2013-01-22

Location : Room 106 Pharmacy Hall, Dankook University

Abstract : Electrically conductive materials provide a platform for the in vitro study of excitable cells, including skeletal myoblast, due to their inherent conductivity and electro activity. We hypothesize that nanopatterned substrates coated in electrically conductive materials will enhance myoblast differentiation and orientation without the need for electrical stimulation or mechanical stress. In this study, we developed a means to coat polyurethane substrates with electrically conductive materials via an electro-beam evaporator.C2C12 cells, a myoblast cell line, were used to assess cell behavior and skeletal muscle differentiation on unpatterned and patterned electrically conductive substrates. Myotube formation and myoblast differentiation gene expression were also assessed on the unpatterned and patterned electrically conductive substrates. We found that patterned substrates enhanced differentiation of linearly aligned myoblasts, suggesting their suitability as a biomimic substrate for in vitro engineering of skeletal muscle tissue.

Tuesday, 04 August 2015 10:10

45 - Molecular Dynamics

Speaker : Chan-Gi Pack, Ph.D. (Research Scientist, Cellular Informatics Laboratory, ASI, RIKEN, 2-1 Hirosawa, Japan)

Date : 2013-02-25

Location: Room 106 Pharmacy Hall, Dankook University

Abstract : The 26S proteasome is a 2.5-MDa multi-subunit protease complex that degrades ubiquitinated proteins in eukaryotic cells. The proteasome is composed of 66 subunits, assisted by multiple dedicated chaperones. In rapidly proliferating yeast and some cancer cells, the 26S proteasome can be localized in the nucleus, in order to ensure the degradation of nuclear proteins. However, it is unclear how and when during the assembly process the proteasome enters the nucleus. Here, we for the first time measured the absolute concentration, dynamics, and complex formation of the 26S proteasome in living yeast cells by fluorescence correlation methods (FCM), a highly sensitive and quantitative method. Interestingly, we found that the 26S proteasome is a highly mobile complex, and that almost all proteasome subunits were stably incorporated into the mega-complex of 26S proteasome in both the cytosol and nucleus. Complex formation was not significantly changed even in an importin-α mutant, suggesting that the proteasome is assembled in the cytosol. Consistent with this, a genetically stabilized 26S proteasome did not exhibit any obvious defects and was distributed normally in the nucleus. These results suggest that the 26S proteasome completes its assembly process in the cytoplasm and translocates into the nucleus through the channel of nuclear pore as 26S large complex. Considering that the 26S proteasome is a fascinating target for pharmaceutical development, the proteasome dynamics revealed by FCM provides a new perspective for developing next-generation proteasome inhibitors.