Cell Transplantation 20(1) Abstracts

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Cell Transplantation, Vol. 20, pp. 5–14, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532819
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Mesenchymal Stem Cells

Dah-Ching Ding,* Woei-Cherng Shyu,†‡ and Shinn-Zong Lin†‡§

*Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan
†Center for Neuropsychiatry, China Medical University & Hospital, Taichung, Taiwan
‡Graduate Institute of Immunology, China Medical University, Taichung, Taiwan
§China Medical University Beigang Hospital, Yunlin, Taiwan

Stem cells have two features: the ability to differentiate along different lineages and the ability of selfrenewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases.

Key words: Mesenchymal stem cells (MSCs); Differentiation; Immune; Homing

Address correspondence to Shinn-Zong Lin, M.D., Ph.D., Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan, R.O.C. Tel: 886-4-22052121; Fax: 886-4-220806666; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Woei-Cherng Shyu, M.D., Ph.D., Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan, R.O.C. Tel: 886-4-22052121, ext. 7811; Fax: 886-4-22052121, ext. 7810; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 15–19, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532828
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Induced Pluripotent Stem (iPS) Cell Research Overview

Shih-Ping Liu,*† Ru-Huei Fu,*‡ Yu-Chuen Huang,§¶ Shih-Yin Chen,§¶ Ying-Jiun Chien,† Chien Yu Hsu,† Chang-Hai Tsai,#** Woei-Cherng Shyu,*‡ and Shinn-Zong Lin*‡††

*Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan
†Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
‡Graduate Institute of Immunology, China Medical University, Taichung, Taiwan
§Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
¶Graduate Institute of Chinese Medical Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan
#Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan
**Department of Healthcare Administration, Asia University, Taichung, Taiwan
††China Medical University Beigang Hospital, Yunlin, Taiwan

Stem cells are capable of self-renewal and differentiation into a wide range of cell types with multiple clinical therapeutic applications. The two most important issues associated with embryonic stem (ES) cells are immune rejection and medical ethics. In 2006, induced pluripotent (iPS) cells were generated from somatic cells via the introduction of four transcriptional factors: OCT4, SOX2, c-MYC, and KLF4. Researchers found that iPS cell morphology, proliferation, surface antigens, gene expression, telomerase activity, and the epigenetic status of pluripotent cell-specific genes were similar to the same characteristics in ES cells. iPS cells are capable of overcoming hurdles associated with ES cells due to their generation from mature somatic cells (e.g., fibroblasts). For this reason, iPS cells are considered an increasingly important cell therapy technology. iPS cell production entails the use of retroviruses, lentiviruses, adenoviruses, plasmid transfections, transposons, or recombinant proteins. In this article we discuss the advantages and limitations of each strategy and address issues associated with clinical trials, including the potential for liver tumor formation and low generation efficiency.

Key words: Induced pluripotent stem cells; Embryonic stem cells; Cell therapy

Address correspondence to Shinn-Zong Lin, MD., Ph.D., Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan. Tel: 886-4-22052121, ext. 6034; Fax: 886-4-220806666; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Woei-Cherng Shyu, M.D., Ph.D., Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan. Tel: 886-4-22052121, ext. 7811; Fax: 886-4-22052121, ext. 7810; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 21–35, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532765
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
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Reproduction: A New Venue for Studying Function of Adult Neurogenesis?1

Benson Wui-Man Lau,*†‡2 Suk-Yu Yau,*†‡2 and Kwok-Fai So*†‡§

*Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PR China
†The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, PR China
‡Research Centre of Heart, Brain, Hormone and Healthy Aging, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PR China
§Joint laboratory for Brain function and Health (BFAH), Jinan University and The University of Hong Kong, GuangZhou, PR China

Adult neurogenesis has been a focus within the past few years because it is a newly recognized form of neuroplasticity that may play significant roles in behaviors and recovery process after disease. Mammalian adult neurogenesis could be found in two brain regions: hippocampus and subventricular zone (SVZ). While it is well established that hippocampal neurogenesis participates in memory formation and anxiety, the physiological function of SVZ neurogenesis is still under intense investigation. Recent studies disclose that SVZ neurogenesis is under regulation of reproductive cues like pheromones. Reciprocally, the newborn neurons may exert their effect on reproductive and maternal behaviors. This review discusses recent understanding of the interrelationship between neurogenesis and reproduction. The studies highlighted in this review illustrate the potential importance of neurogenesis in reproductive function and will provide new insights for the significance of adult neurogenesis.

Key words: Neurogenesis; Reproductive function; Mammalian brain; Interrelationship

1This article represents part of a thesis submitted by B. W. M. Lau to The University of Hong Kong for the partial fulfillment of the Ph.D. degree.
2These authors provided equal contribution to this work.
Address correspondence to Professor Kwok-Fai So, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, PR China. Tel: (852)2819-9216; Fax: (852)2817-0857; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 37–47, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532756
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
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Differentiation of Stem Cells: Strategies for Modifying Surface Biomaterials

Ru-Huei Fu,*†1 Yu-Chi Wang,‡1 Shih-Ping Liu,*§ Chin-Mao Huang,* Yun-Han Kang,* Chang-Hai Tsai,¶# Woei-Cherng Shyu,*†2 and Shinn-Zong Lin*†**2

*Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan
†Graduate Institute of Immunology, China Medical University, Taichung, Taiwan
‡Biotechplex Corp., San Diego, CA, USA
§Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
¶Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan
#Department of Healthcare Administration, Asia University, Taichung, Taiwan
**China Medical University Beigang Hospital, Yunlin, Taiwan

Stem cells are a natural choice for cellular therapy because of their potential to differentiate into a variety of lineages, their capacity for self-renewal in the repair of damaged organs and tissues in vivo, and their ability to generate tissue constructs in vitro. Determining how to efficiently drive stem cell differentiation to a lineage of choice is critical for the success of cellular therapeutics. Many factors are involved in this process, the extracellular microenvironment playing a significant role in controlling cellular behavior. In recent years, researchers have focused on identifying a variety of biomaterials to provide a microenvironment that is conducive to stem cell growth and differentiation and that ultimately mimics the in vivo situation. Appropriate biomaterials support the cellular attachment, proliferation, and lineage-specific differentiation of stem cells. Tissue engineering approaches have been used to incorporate growth factors and morphogenetic factors—factors known to induce lineage commitment of stem cells—into cultures with scaffolding materials, including synthetic and naturally derived biomaterials. This review focuses on various strategies that have been used in stem cell expansion and examines modifications of natural and synthetic materials, as well as various culture conditions, for the maintenance and lineage-specific differentiation of embryonic and adult stem cells.

Key words: Stem cells; Biomaterials; Tissue engineering; Extracellular matrix (ECM)

1These authors provided equal contribution to this work.
2These authors provided equal contribution to this work.
Address correspondence to Shinn-Zong Lin, M.D., Ph.D., Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan. Tel: 886-4-22052121, ext. 6034; Fax: 886-4-22080666; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Woei-Cherng Shyu, M.D., Ph.D., Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan. Tel: 886-4-22052121, ext. 7811; Fax: 886-4-22052121, ext. 7810; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 49–62, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532792
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Functional Cells Cultured on Microcarriers for Use in Regenerative Medicine Research

Li-Yi Sun,*1 Shinn-Zong Lin,†1 Yuan-Sheng Li,‡ Horng-Jyh Harn,§¶ and Tzyy-Wen Chiou‡

*Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
†Center for Neuropsychiatry, China Medical University and Hospital and Beigang Hospital, Taichung and Yun-Lin, Taiwan
‡Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan
§Department of Pathology, China Medical University and Hospital, Taichung, Taiwan
¶Department of Medicine, China Medical University, Taichung, Taiwan

Microcarriers have been successfully used for many years for growing anchorage-dependent cells and as a means of delivering cells for tissue repair. When cultured on microcarriers, the number of anchorage-dependent cells, including primary cells, can easily be scaled up and controlled to generate the quantities of cells necessary for therapeutic applications. Recently, stem cell technology has been recognized as a powerful tool in regenerative medicine, but adequate numbers of stem cells that retain their differentiation potential are still difficult to obtain. For anchorage-dependent stem cells, however, microcarrier-based suspension culture using various types of microcarriers has proven to be a good alternative for effective ex vivo expansion. In this article, we review studies reporting the expansion, differentiation, or transplantation of functional anchorage-dependent cells that were expanded with the microcarrier culture system. Thus, the implementation of technological advances in biodegradable microcarriers, the bead-to-bead transfer process, and appropriate stem cell media may soon foster the ability to produce the numbers of stem cells necessary for cell-based therapies and/or tissue engineering.

Key words: Microcarriers; Stem cell; Expansion; Transplantation

1These authors provided equal contribution to this work.
Address correspondence to Prof. Tzyy-Wen Chiou, Ph.D., Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Rd., Shou-Feng, Hualien, Taiwan, ROC. Tel: 886-3-8633638; Fax: 886-3-8630398; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Dr. Horng-Jyh Harn, M.D., Ph.D., Pathology Department, China Medical University & Hospital, 2 Yuh-Der Road, Taichung City, Taiwan, ROC. Tel: 886-4-22052121, ext. 2661; Fax: 886-4-22052121, ext. 2566; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 63–70, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532864
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
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Novel Approach by Nanobiomaterials in Vascular Tissue Engineering

Huey-Shan Hung,*† Hui-Chen Chen,† Chang-Hai Tsai,‡§ and Shinn-Zong Lin*¶#

*Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan
†Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
‡Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan
§Department of Healthcare Administration, Asia University, Taichung, Taiwan
¶Graduate Institute of Immunology, China Medical University, Taichung, Taiwan
#China Medical University Beigang Hospital, Yunlin, Taiwan

Interactions between vascular endothelial cells (ECs) and biomaterials are important for engineered tissue substitute. The modification of biomaterial surfaces are designed to modulate EC adhesion and responses in order to improve implantation success rate. Specifically, it has now been well established that increased vascular tissue regeneration can be achieved on almost any surface by employing novel nanofabricated surface features. To enhance EC adhesion and growth, material surfaces have been modified with physicochemical and mechanical properties, such as bioactive molecules from the matrix, peptides, and/or growth factors to control EC behavior. The advances in nanotechnology can bring additional functionality to vascular tissue engineering, optimize internal vascular graft surface, help to direct the differentiation of stem cells into the vascular cell phenotype, and, most importantly, also provide a biomaterials-based cellularization process. Nanomaterials could promote in situ endothelialization by mobilizing endothelial progenitor cells (EPCs) from the bone marrow, by encouraging cell-specific adhesion to the vascular graft, and, once attached, by controlling the proliferation and differentiation of these cells. Interaction between different cell types and extracellular matrix continue to be a principal source of inspiration for material biological function and, therefore, the understanding of the molecular mechanism trigger by the interaction is discussed.

Key words: Nanobiomaterials; Vascular endothelial cells (ECs); Tissue engineering; Nanotechnology

Address correspondence to Shinn-Zong Lin, MD., Ph.D., Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan. Tel: 886-4-22052121; Fax: 886-4-220806666; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 71–83, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532747
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Botanical Drugs and Stem Cells

Po-Cheng Lin,*†1 Li-Fu Chang,*1 Po-Yen Liu,‡1 Shinn-Zong Lin,†§1 Wan-Chen Wu,¶ Wuen-Shyong Chen,# Chang-Hai Tsai,**††1 Tzyy-Wen Chiou,*1 and Horng-Jyh Harn‡‡§§1

*Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan
†Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan
‡Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
§China Medical University Beigang Hospital, Yun-Lin, Taiwan
¶Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
#Department of Stem Cell Applied Technology, Gwo Xi Stem Cell Applied Technology, Hsinchu, Taiwan
**Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan
††Department of Healthcare Administration, Asia University, Taichung, Taiwan
‡‡Department of Pathology, China Medical University and Hospital, Taichung, Taiwan
§§Department of Medicine, China Medical University, Taichung, Taiwan

The potential to generate virtually any differentiated cell type from stem cells offers the possibility of creating new sources of cells for regenerative medicine. To realize this potential, it will be essential to control stem cell differentiation. Chinese herbal medicine is a major aspect of traditional Chinese medicine and is a rich source of unique chemicals. As such, individual herbs or extracts may play a role in the proliferation and differentiation of stem cells. In this review, we discuss some of the Chinese herbal medicines that are used to treat human diseases such as neuronal degenerative diseases, cardiovascular diseases, and osteoporosis. We also describe the relationship between Chinese herbal medicines and stem cell regulation.

Key words: Stem cells; Traditional Chinese medicine (TCM); Neuronal degenerative diseases; Cardiovascular diseases; Osteoporosis

1These authors provided equal contribution to this work.
Address correspondence to Dr. Tzyy-Wen Chiou, Ph.D., Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Rd., Shou-Feng, Hualien, Taiwan, R.O.C. Tel: 886-3-8633638; Fax: 886-3-8630262; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Dr. Horng-Jyh Harn, Department of Pathology, China Medical University and Hospital, 2 Yuh-Der Road, Taichung, Taiwan, 40447, R.O.C. Tel: 886-4-22052121, ext. 2661; Fax: 886-4-22052121, ext. 2566; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 85–94, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532855
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Treatment of Neurodegenerative Disorders Using Umbilical Cord Blood and Menstrual Blood-Derived Stem Cells

Paul R. Sanberg,*† David J. Eve,* Alison E. Willing,* Svitlana Garbuzova-Davis,* Jun Tan,*‡ Cyndy D. Sanberg,§ Julie G. Allickson,¶ L. Eduardo Cruz,# and Cesar V. Borlongan*

*Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA
†Office of Research and Innovation, University of South Florida, Tampa, FL, USA
‡Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry & Behavioral Medicine, University of South Florida, Tampa, FL, USA
§Saneron CCEL Therapeutics, Inc., Tampa, FL, USA
¶Cryo-Cell International, Inc., Oldsmar, FL, USA
#Cryopraxis, Cell Praxis, BioRio, Po´de Biotechnologia do Rio de Janeiro, Rio de Janeiro, Brazil

Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer’s disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

Key words: Umbilical cord blood; Menstrual-derived stem cells; Stroke; Alzheimer’s disease; Amyotrophic lateral sclerosis; Sanfilippo syndrome

Address correspondence to Paul R. Sanberg, Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel: 813-974-3154; Fax: 813-974-3078; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation
, Vol. 20, pp. 95–97, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532800
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Vascular Protection and Restorative Therapy in Ischemic Stroke

Toru Yamashita, Kentaro Deguchi, Shoko Nagotani, and Koji Abe

Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

Possible strategies for treating stroke include: 1) thrombolytic therapy with tissue plasminogen activator (tPA): restoring cerebral blood flow in the acute phase of ischemic stroke but sometimes causing hemorrhagic transformation (HT); 2) stem cell therapy: the repair of disrupted neuronal networks with newly born neurons in the chronic phase of ischemic stroke. Firstly, we estimated the vascular protective effect of a free radical scavenger, edaravone, in the tPA-treated rat model of middle cerebral artery occlusion. Edaravone prevented dramatically decreased the hemorrhagic transformation and improved the neurologic score and survival rate of tPA-treated rats. Secondly, we attempted to restore brain tissue using a novel biomaterial, polydimethysiloxane-tetraethoxysilane (PDMS-TEOS) hybrid with or without vascular endothelial growth factor (VEGF), and we could show that implantation of a PDMS-TEOS scaffold with VEGF might be effective for treating old brain infarction or trauma. In the future, we will combine these strategies to develop more effective therapies for treatment of strokes.

Key words: Cerebral ischemia; Tissue plasminogen activator (tPA); Free radicals; Neural stem cells; Scaffold

Address correspondence to Koji Abe, Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama, 700-8558 Japan. Tel: +81-86-235-7365; Fax: +81-86-235-7368; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 99–111, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532846
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Adult Hippocampal Neurogenesis: A Possible Way How Physical Exercise Counteracts Stress

Suk-Yu Yau,*†‡1,2 Benson Wui-Man Lau,*†‡2 and Kwok-Fai So*†‡§

*Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PR China
†The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, PR China
‡Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, PR China
§Joint laboratory for Brain function and Health (BFAH), Jinan University andThe University of Hong Kong, GuangZhou, PR China

It was considered that neurogenesis only occurred during the embryonic and developmental stage. This view has greatly changed since the discovery of adult neurogenesis in two brain regions: the hippocampus and the olfactory bulb. Recently, it is suggested that altered hippocampal neurogenesis is related to pathophysiology of mood disorders and mechanism of antidepressant treatments. Accumulating knowledge about the effects of physical exercise on brain function suggests a special role of adult hippocampal neurogenesis in cognitive and mental health, even though the functional significance of adult neurogenesis is still debated. The beneficial effects of running correlating with increased adult neurogenesis may provide a hint that newborn neurons may be involved, at least in part, in the counteractive mechanism of physical exercise on stress-related disorders, like depression. The present review provides an overview of recent findings to emphasize the possible involvement of hippocampal neurogenesis in mediating the beneficial effects of physical exercise on counteracting stress.

Key words: Hippocampal neurogenesis; Physical exercise; Stress; Dendritic plasticity

1This article represents part of a thesis submitted by S.-Y. Yau to The University of Hong Kong for the partial fulfillment of the Ph.D. degree.
2These authors provided equal contribution to this work.
Address correspondence to Professor Kwok-Fai So, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, PR China. Tel: (852)2819-9216; Fax: (852)2817-0857; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 113–120, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532837
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
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An Overview of Concepts for Cancer Stem Cells

Shih-Yin Chen,*† Yu-Chuen Huang,*† Shih-Ping Liu,‡§ Fuu-Jen Tsai,*¶ Woei-Cherng Shyu,‡ and Shinn-Zong Lin‡#

*Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
†Graduate Institute of Chinese Medical Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan
‡Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan
§Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
¶Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan
#China Medical University Beigang Hospital, Yunlin, Taiwan

For many years, cancer research has focused on the adult stem cells present in malignant tumors. It is believed that current cancer treatments sometimes fail because they do not target these cells. According to classic models of carcinogenesis, these events can occur in any cell. In contrast, the cancer stem cell (CSC) hypothesis states that the preferential targets of oncogenic transformation are tissue stem cells or early progenitor cells that have acquired the potential for self-renewal. These tumor-initiating cells, or CSCs, in turn, are characterized by their ability to undergo self-renewal, a process that drives tumorigenesis and differentiation, which contributes to the cellular heterogeneity of tumors. Herein, we discuss the definitions and properties of CSCs in the major human cancers.

Key words: Cancer stem cell (CSC); Adult stem cells; Tumor-initiating cells; Self-renewal

Address correspondence to Shinn-Zong Lin, M.D., Ph.D., Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan. Tel: 886-4-22052121, ext. 6034; Fax: 886-4-220806666; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Woei-Cherng Shyu, M.D., Ph.D., Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan. Tel: 886-4-22052121, ext. 7811; Fax: 886-4-22052121, ext. 7810; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 121–125, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532774
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
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The Role of Cancer Stem Cells (CD133+) in Malignant Gliomas

Der-Yang Cho,*† Shinn-Zong Lin,*† Wen-Kuang Yang,* Den-Mei Hsu,* Hung-Lin Lin,* Han-Chung Lee,* Wen-Yeun Lee,* and Shao-Chih Chiu†

*Department of Neurosurgery, Neuropsychiatric Center, Cell/Gene Therapy Research Laboratory, China Medical University Hospital, Taichung, Taiwan
†Graduate Institute of Immunology, China Medical University, Taichung, Taiwan

Malignant gliomas, particularly glioblastoma multiforme (GBM) tumors, are very difficult to treat by conventional approaches. Although most of the tumor mass can be removed by surgical resection, radiotherapy, and chemotherapy, it eventually recurs. There is growing evidence that cancer stem cells (CSCs) play an important role in tumor recurrence. These stem cells are radioresistant and chemoresistant. The most commonly used tumor marker for CSCs is CD133. The amount of CSC component is closely correlated with tumor malignancy grading. Isolating, identifying, and treating CSCs as the target is crucial for treating malignant gliomas. CSC-associated vascular endothelial growth factor (VEGF) promotes tumor angiogenesis, tumor hemorrhage, and tumor infiltration. Micro-RNA (miRNA) plays a role in CSC gene expression, which may regulate oncogenesis or suppression to influence tumor development or progression. The antigenesis of CSCs and normal stem cells may be different. The CSCs may escape the T-cell immune response. Identifying a new specific antigen from CSCs for vaccine treatment is a key point for immunotherapy. On the other hand, augmented treatment with radiosensitizer or chemosensitizer may lead to reduction of CSCs and lead to CSCs being vulnerable to radiotherapy and chemotherapy. The control of signaling pathway and cell differentiation to CSC growth is another new hope for treatment of malignant gliomas. Although the many physiological behavioral differences between CSCs and normal stem cells are unclear, the more we know about these differences the better we will be able to treat CSCs effectively.

Key words: Cancer stem cells (CSCs); CD133+; Glioblastoma multiforme (GBM); Malignant gliomas; Micro-RNA (miRNA); Signaling pathway

Address correspondence to Wen-Kuang Yang, M.D., Ph.D., Professor, Cell/Gene Therapy Research Laboratory, China Medical University Hospital, No. 2 Yu-Der Road, Taichung, Taiwan, R.O.C. Tel: 886-42-2052121, ext. 2779; Fax: 886-42-2079649, ext. 5035; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 121–131, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532783
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Brief Communication

Using Self-Assembled Nanomaterials to Inhibit the Formation of Metastatic Cancer Stem Cell Colonies In Vitro

Patrick M. T. Ling,* Sunny W. H. Cheung,* David K. C. Tay,* and Rutledge G. Ellis-Behnke*†‡

*Department of Anatomy, Lika Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
†Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
‡Nanomedicine Translational Think Tank, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

The isolation of cells with stem-like properties from prostate tumors suggests the presence of a cancer stem cell (CSC) population, which may account for the initiation, progression, and metastasis as well as drug resistance of the disease. We hypothesized that containing, or at least immobilizing, the CSCs in a nanoself-assembling material might help prevent prostate tumor progression or metastasis. CSCs were plated in three conditions: 1) placed in 1% concentration self-assembled peptide (SAP) preequilibrate with culture medium; 2) placed in 3% concentration SAP preequilibrate with culture medium; and 3) in nonadherent culture. All were grown for 14 days, after which the cells in both 1% and 3% concentrations were washed out of the SAP and grown for an additional 14 days. Here we report that CSCs from prostate cancer cell lines remained quiescent for more than 28 days when embedded in SAP. When the prostate CSCs were embedded in 1% and 3% SAP, most of the CSCs remained single cells 14 days after plating in a nonadherent plate; no prostaspheres could be detected 14 days after plating, suggesting that self-renewal was significantly suppressed. In the controls, prostate CSCs began to divide 1 day after plating in a nonadherent plate and prostaspheres were visible at day 10, indicating the active self-renewal property of the prostate CSCs. Our findings suggest that SAP can completely inhibit a prostate CSC from self-renewal while preserving its viability and CSC property. Therefore, SAP may be an effective nanomaterial for inhibiting cancer progression and metastasis to stop the progression during treatment and removal.

Key words: Prostate cancer; Stem cell; Self-assembling peptide; Nanomedicine

Address correspondence to Rutledge Ellis-Behnke, Ph.D., Nanomedicine Translational Think Tank, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Theodor-Kutzer-Ulfer 1-3, Mannheim 68167, Germany. Tel: +49(9)621 383 6078; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it