The "low-oxygen process" is employed to cultivate, proliferate, and transplant mesenchymal stem cells. Based on the related basic and translational research, the center has published more than 20 papers in SCI journals, proving that mesenchymal stem cells cultured under hypoxic condition can undergo allotransplantation for the treatment of acute hepatitis. Its molecular biologic mechanism is for cells to secrete anti-inflammatory molecules, such as IL-1Ra, to inhibit inflammation. The results of this study can be used in clinical trials to provide a new treatment for acute or falminant hepatitis. At present, the center is also actively carrying out translational research and applying relevant patent technology to clinical therapy. Preclinical animal trials for various indications have been completed, including the use of hypoxic mesenchymal stem cells in the treatment of lower limb ischemia, coronary artery stenosis, fulminant hepatitis, and graft versus host disease (GVHD), as well as to promote fracture healing, and recovery from degenerative arthritis and Achilles tendon. One of the most important achievements of the team is to apply the research results of xenotransplantation of hypoxic mesenchymal stem cells to clinical trials. Currently, the phase I clinical trial for the treatment of lower limb ischemia with allogenic low oxygen mesenchymal stem cells has been approved by the Ministry of Health and Welfare. And now, 18 patients have been admitted, of which no patients have any side effects associated with the therapy, and some have shown stem cell therapy efficacy.

 

Cancer stem cells, a small group of cells that have the ability to renew themselves in the tumor, are now isolated from a variety of tumor tissues. The latest research shows that cancer stem cells are the key to resistance, recurrence, and metastasis produced after cancer treatment. Our past research has clearly pointed out the important message transduction or molecular mechanism of cancer stem cell resistance, recurrence, and metastasis in colon cancer and lung cancer. The center will focus on the development of drugs targeting tumor stem cells screening platforms, including the establishment of system platforms for the isolation, culture, and screening of colorectal cancer stem cells and lung cancer (non-small cell lung cancer) stem cells.

According to epidemiological research, the effects of disease induced by PM2.5 include: early death, bronchitis, asthma, cardiovascular disease, and lung cancer. Whether long-term or short-term exposure to air pollutants can raise the incidence of disease and even increase the risk of death. At present, our research team is dedicated to epidemiology, animal experiments, experiments on the related mechanism for causing mortality, and other studies. In the years to come, the center is to focus on the development of stem cells or Chinese herbal medicine targeted therapy and other treatment strategies. Early detection of the symptoms of disease progression and appropriate treatment are to be carried out to improve the mortality of the disease caused by PM2.5, in the expectation of making valuable contributions and realizing therapeutic potential against PM2.5.

Adult stem cells exist in different tissues and have a type of cells that regenerate the potential functions of various tissues and organs. They can be divided and differentiated into a variety of specialized cells, and can use self-renewal to provide more stem cells. Our present study focuses on the in vivo small intestinal epithelial stem cells and bone marrow mesenchymal stem cells. Since small intestinal epithelium has the ability to quickly renew itself, it is an ideal system for studying adult stem cells. The small intestinal epithelium consists of the villus and the recess, and the small intestinal stem cells at the bottom of the small intestinal recess are the source of their continuous renewal. In recent years, the discovery of small intestinal stem cell markers represented by Lgr5, the isolation and culture of Lgr5+ small intestinal stem cells, and the emergence of multiple transgenic mouse models have significantly promoted the research on the regulation of self-renewal and differentiation of intestinal stem cells, which allows people to know more about the molecular mechanism to determine the fate of the small intestinal stem cells. My research has focused on the roles of Wnt, BMP, Notch, EGF, and other signals in the regulation of intestinal stem cell regeneration and canceration. Bone marrow mesenchymal stem cells (MSCs) in an adult body can differentiate into osteoblasts, chondrocytes, and adipocytes via the culture in vitro. But the function in the living body is not clear. We used Leptin receptor+ in the experiment as a marker of mesenchymal stem cells to study the role of this cell population in bone development and adult bone regeneration.

Lung cancer stem cells have tough vitality, and their energy sources are different from those of common cancer cells. Our previous findings expressly indicated that lung cancer stem cells can survive in animals through the expression of Collagen XVII and their molecular mechanisms. The center is to delve into the source of the metabolome of lung cancer stem cells in the years to come.

Snail protein can change the metastasis function of breast cancer cells during their metastasis. The interaction of SRC and ERα proteins can allow breast cancer cells to spread to other organs of the animal. This animal model can be used to explore the protein molecules needed for metastasis of breast cancer cells and their participation in the mechanism.

Arthritis is a global chronic epidemic. According to the World Health Organization (WHO), about 350 million people worldwide are suffering from arthritis. Clinically, the methods used for surgical treatment of skeletal muscle injury include autografts, allografts, and synthetic substitutes made of metal, ceramics and / or conventional hydrogels. However, they each have their own limitations, and most of them have a problem with the poor integration of the surrounding tissues. We use the self-healing strategy to develop a new generation of biomedical materials, which not only can allow materials and tissues to have good integration performance to improve the surgical outcomes, but the self-healing properties of materials can be developed into fine bioinks for 3D printing to be applied to the tissue engineering and cell therapy.

The promotion of articular cartilage repair is an important issue in regenerative medicine. The commercial cellular scaffold products used clinically is MACI® and Bioseed-C®. However, commercial scaffolds on the market lack the structural mechanical properties that can be maintained for long periods of time. What’s more, commercial scaffolds currently cannot increase the number of cells. In addition, the cells cannot be evenly distributed in the scaffolds, causing the patients’ joints to be unable to be compatible with the present scaffold products for long. Therefore, it is important to develop cellular scaffolds that can help patients with articular cartilage damage to further make the scaffold compatible with the patient’s tissues for long duration. Our laboratory aims to build mechanically more powerful newborn cartilage. The strategy has two parts. The first is to use improved culture methods, such as small chemical molecules, growth hormone stimulation, hypoxic culture, and physical stimulation, to make mesenchymal stem cells more likely to function as chondrocytes, or to cultivate a large number of chondrocytes. The second is to design new materials more suitable for cartilage development. We are more interested in using new nano glue to develop more convenient cellular scaffolds with effective manufacturing strategies.

Skin and its appendages are ideal models for interdisciplinary exploration of cell tissue regeneration because their regeneration cycles are short and their functionality displayed is highly correlated with their microstructures. The center associate research fellow Wen-tau Juan and his team used feathers with a highly complex structure as a model system to explore the features’ functionality and physical structure characteristics, design principles, and corresponding regeneration processes. This interdisciplinary research can enhance people's understanding of the internal natural structure of skin appendages that have evolved for over 100 million years, and gain knowledge of the natural law of achieving their versatility, as well as apply the first-hand information to the emerging research and development of skin and hair-related regenerative medicine and stem cell therapy. The center project assistant professor Dr. Ming-hsing Lei collaborated with Fellow Cheng-ming Chuong in studying on how skin dispersion and skin cells can form skin and hair follicle structures through self-organization with tissue engineering strategies, stating that cells can form tissues and organs by physicochemical coupling and interaction. This experience can be employed to study bone injury; oral, neural, and cardiovascular stem cells, and regenerative medicine.

The regeneration blastema formed by wounded tissues requires stem cells, the appropriate extracellular matrix, and proper positional information to develop into a correct structure. We focus on the regeneration of skin appendages, aiming to study how to form the blastema and preserve the regional specific pattern development processes. The diversity of avian feathers is a good model animal to delve into the regulation mechanism of the axon’s specific molecules. We have presented the dermal papilla cells extracted from avian feathers as a follicle neogenesis model and explored the epigenetic regulation of the stability of organogenesis, in an attempt to reconstruct or induce this factor to give appropriate environmental stimuli to bring out the correct type of regeneration.

Skin area specialization constitutes an important mechanism to make skin multifunctional. Disability can lead to many diseases but the molecular mechanism to regulate skin area specialization still remains unknown. Center honorary director Cheng-ming Chuong and his team, from the perspective of epigenetics, integrated next-generation sequencing (NGS) technology, including RNA-seq, ChIP-seq, ATAC-seq, NG Capture-C, MeDIP-seq, and MRE-seq to comprehensively explore how the high-level chromatin structure and DNA methylation regulate the genetic transcription of epidermal precursor cells and hair follicle stem cells, in an effort to further control the regional specialization, development, and regeneration of the skin. It is believed that this study can offer an epigenetic mechanism for organ development and specialization, and strengthen the theoretical basis for regenerative medicine and stem cell therapy.

The specialized mechanism of the follicle cell population is the key to skin regeneration medicine. However, human-induced hair follicle cell differentiation still has a way to go in that the molecular mechanism to induce hair follicle cell specialization is still a largely uncharted area. Based on the self-developed epidermal tissue recombinant technology combined with the systematic analysis of epigenetics and bioinformatics, our team has identified several pattern growth factors that are abundant in the critical period of follicle cell mass specialization. The team is now using model animals to look into the performance and function of these factors in vivo. Through the analysis of these regulatory factors, we will be able to find out the key factors inducing follicle cell mass differentiation, and make breakthroughs in burn treatment, skin tissue reconstruction, and other technologies.

Understanding the specialized mechanism of the skin appendages in different parts of the body, and their specific arrangement patterns, can provide the important application basis for regenerative medicine and help stem cells produce the organs with correct forms and functions in the regeneration process. With the evolution of the next generation sequencing, we can gain a deeper understanding of the molecular and epigenetic mechanisms of specialization and arrangement of skin appendages by using bioinformatics technology, which has great benefits for human health and medical development.