Cell Transplantation 20(4) Abstracts

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Cell Transplantation, Vol. 20, pp. 475–491, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X528102
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Bone Marrow Mesenchymal Stem Cells and Electroacupuncture Downregulate the Inhibitor Molecules and Promote the Axonal Regeneration in the Transected Spinal Cord of Rats

Ying Ding,* Qing Yan,* Jing-Wen Ruan,† Yan-Qing Zhang,* Wen-Jie Li,* Xiang Zeng,* Si-Fan Huang,* Yu-Jiao Zhang,* Shirlene Wang,‡ Hongxin Dong,‡ and Yuan-Shan Zeng*

*Division of Neuroscience, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
†Department of Acupuncture of the first Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
‡Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
§Center for Stem Cell Biology and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
Institute of Spinal Cord Injury, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

Our previous study has reported that electroacupuncture (EA) promotes survival, differentiation of bone marrow mesenchymal stem cells (MSCs), and functional improvement in spinal cord-transected rats. In this study, we further investigated the structural bases of this functional improvement and the potential mechanisms of axonal regeneration in injured spinal cord after MSCs and EA treatment. Five experimental groups, 1) sham control (Sham-control); 2) operated control (Op-control); 3) electroacupuncture treatment (EA); 4) MSCs transplantation (MSCs), and 5) MSCs transplantation combined with electroacupuncture (MSCs + EA), were designed for this study. Western blots and immunohistochemical staining were used to assess the fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs) proteins expression. Basso, Beattie, Bresnahan (BBB) locomotion test, cortical motor evoked potentials (MEPs), and anterograde and retrograde tracing were utilized to assess cortical-spinal neuronal projection regeneration and functional recovery. In the MSCs + EA group, increased labeling descending corticospinal tract (CST) projections into the lesion site showed significantly improved BBB scales and enhanced motor evoked potentials after 10 weeks of MSCs transplant and EA treatment. The structural and functional recovery after MSCs + EA treatment may be due to downregulated GFAP and CSPGs protein expression, which prevented axonal degeneration as well as improved axonal regeneration.

Key words: Spinal cord transection; Bone marrow mesenchymal stem cells; Electroacupuncture; Transplantation; Axonal regeneration

Address correspondence to Yuan-Shan Zeng, M.D., Ph.D., Division of Neuroscience, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, 74# Zhongshan 2nd Road, Guangzhou 510080, China. Tel: 001-86-20-87332698; Fax: 001-86-20-87332698; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Hongxin Dong, M.D., Ph.D., Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611-3008, USA. Tel: 312-926-2323; Fax: 312-926-8080; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 493–502, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X536464
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Characterization of Axon Formation in the Embryonic Stem Cell-Derived Motoneuron

Hung-Chuan Pan,*†1 Ya-Ting Wu,‡1 Shih-Cheng Shen,‡ Chi-Chung Wang,§ Ming-Shiun Tsai, Fu-Chou Cheng,# Shinn-Zong Lin,**††‡‡ Ching-Wen Chen,‡ Ching-San Liu,§§ and Hong-Lin Su ‡

*Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan
†Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
‡Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan
§Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipai City, Taiwan
Department of Bioindustry Technology, Da-Yeh University, Changhua, Taiwan
#Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
**Center for Neuropsychiatry, China Medical University and Hospital, Taichung, Taiwan
††China Medical University Beigang Hospital, Yunlin, Taiwan
‡‡Department of Immunology, China Medical University, Taichung, Taiwan
§§Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan
Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan

The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuronspecific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP+ neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

Key words: Embryonic stem cell; Axon formation; Motoneuron; Neural differentiation

1These authors provided equal contribution to this work.
Address correspondence to Hong-Lin Su, 250, Kuo-Kuang Rd, Taichung, 402, Taiwan. Tel: 886-4-22840416; Fax: 886-4-22854391; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 503–513, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X546580
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Medical Terminations of Pregnancy: A Viable Source of Tissue for Cell Replacement Therapy for Neurodegenerative Disorders

C. M. Kelly,*1 S. V. Precious,*1 E. M. Torres,* A. W. Harrison,† D. Williams,‡ C. Scherf,‡ U. M. Weyrauch,* E. L. Lane,* N. D. Allen,* R. Penketh,‡ N. N. Amso,‡ P. J. Kemp,† S. B. Dunnett,* and A. E. Rosser*§

*Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK
†Division of Pathophysiology and Repair, School of Biomedical Sciences, Cardiff University, Cardiff, UK
‡Department of Obstetrics and Gynaecology, School of Medicine, Cardiff University, Cardiff, UK
§Departments of Neurology and Genetics, School of Medicine, Cardiff University, Cardiff, UK

“Proof-of-principle” that cell replacement therapy works for neurodegeneration has been reported, but only using donor cells collected from fetal brain tissue obtained from surgical terminations of pregnancy. Surgical terminations of pregnancy represent an increasingly limited supply of donor cells due to the tendency towards performing medical termination in much of Europe. This imposes a severe constraint on further experimental and clinical cell transplantation research. Therefore, we explore here the feasibility of using medical termination tissue as a donor source. Products of conception were retrieved from surgical terminations over the last 7 years and from medical terminations over the last 2.5 years. The number of collections that yielded fetal tissue, viable brain tissue, and identifiable brain regions (ganglionic eminence, ventral mesencephalon, and neocortex) were recorded. We studied cell viability, cell physiological properties, and differentiation potential both in vitro and following transplantation into the central nervous system of rodent models of neurodegenerative disease. Within equivalent periods, we were able to collect substantially greater numbers of fetal remains from medical than from surgical terminations of pregnancy, and the medical terminations yielded a much higher proportion of identifiable and dissectible brain tissue. Furthermore, we demonstrate that harvested cells retain the capacity to differentiate into neurons with characteristics appropriate to the region from which they are dissected. We show that, contrary to widespread assumption, medical termination of pregnancy-derived fetal brain cells represent a feasible and more readily available source of human fetal tissue for experimental cell transplantation with the potential for use in future clinical trials in human neurodegenerative disease.

Key words: Human fetal tissue; Neural transplantation

1These authors are joint first authors.
Address correspondence to Claire M. Kelly, Brain Repair Group, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK. Tel: (+44) (0) 2920 874115; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 515–522, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X532729
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Functional Endothelial Progenitor Cells From Cryopreserved Umbilical Cord Blood

Ruei-Zeng Lin,*† Alexandra Dreyzin,* Kristie Aamodt,* Andrew C. Dudley,†‡ and Juan M. Melero-Martin*†

*Department of Cardiac Surgery, Children’s Hospital Boston, Boston, MA, USA
†Department of Surgery, Harvard Medical School, Boston, MA, USA
‡Vascular Biology Program, Children’s Hospital Boston, Boston, MA, USA

Umbilical cord blood (UCB) is recognized as an enriched source of endothelial progenitor cells (EPCs) with potential therapeutic value. Because cryopreservation is the only reliable method for long-term storage of UCB cells, the clinical application of EPCs depends on our ability to acquire them from cryopreserved samples; however, the feasibility of doing so remains unclear. In this study we demonstrate that EPCs can be isolated from cryopreserved UCB-derived mononuclear cells (MNCs). The number of outgrowth EPC colonies that emerged in culture from cryopreserved samples was similar to that obtained from fresh UCB. Furthermore, EPCs obtained from cryopreserved MNCs were phenotypically and functionally indistinguishable from freshly isolated ones, including the ability to form blood vessels in vivo. Our results eliminate the necessity of performing cell isolation procedures ahead of future clinical needs and suggest that EPCs derived from cryopreserved UCB may be suitable for EPC-related therapies.

Key words: Endothelial progenitor cells (EPCs); Cord blood; Cryopreservation; Vascularization; Regenerative medicine

Address correspondence to Dr. Juan M. Melero-Martin, Department of Cardiac Surgery, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Ave., Enders 349.1, Boston, MA 02115, USA. Tel: (617) 919-3072; Fax: (617) 730-0235; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 523–534, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X528111
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Human Amniotic Epithelial Cells Induce Localized Cell-Mediated Immune Privilege In Vitro: Implications for Pancreatic Islet Transplantation

Khalid M. Qureshi,* Robert J. Oliver,* Michelle B. Paget,* Hilary E. Murray,* Clifford J. Bailey,† and Richard Downing*

*The Islet Research Laboratory, Worcester Clinical Research Unit, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
†School of Life and Health Sciences, Aston University, Birmingham, UK

Chronic systemic immunosuppression in cell replacement therapy restricts its clinical application. This study sought to explore the potential of cell-based immune modulation as an alternative to immunosuppressive drug therapy in the context of pancreatic islet transplantation. Human amniotic epithelial cells (AEC) possess innate anti-inflammatory and immunosuppressive properties that were utilized to create localized immune privilege in an in vitro islet cell culture system. Cellular constructs composed of human islets and AEC (islet/AEC) were bioengineered under defined rotational cell culture conditions. Insulin secretory capacity was validated by glucose challenge and immunomodulatory potential characterized using a peripheral blood lymphocyte (PBL) proliferation assay. Results were compared to control constructs composed of islets or AEC cultured alone. Studies employing AEC-conditioned medium examined the role of soluble factors, and fluorescence immunocytochemistry was used to identify putative mediators of the immunosuppressive response in isolated AEC monocultures. Sustained, physiologically appropriate insulin secretion was observed in both islets and islet/AEC constructs. Activation of resting PBL proliferation occurred on exposure to human islets alone but this response was significantly (p < 0.05) attenuated by the presence of AEC and AEC-conditioned medium. Mitogen (phytohaemagglutinin, 5 μg/ml)-induced PBL proliferation was sustained
on contact with isolated islets but abrogated by AEC, conditioned medium, and the islet/AEC constructs. Immunocytochemical analysis of AEC monocultures identified a subpopulation of cells that expressed the proapoptosis protein Fas ligand. This study demonstrates that human islet/AEC constructs exhibit localized immunosuppressive properties with no impairment of β-cell function. The data suggest that transplanted islets may benefit from the immune privilege status conferred on them as a consequence of their close proximity to human AEC. Such an approach may reduce the need for chronic systemic immunosuppression, thus making islet transplantation a more attractive treatment option for the management of insulindependent diabetes.

Key words: Human islets; Human amniotic epithelial cells; Immune privilege; Rotational cell culture system; Peripheral blood lymphocytes; Immunosuppression; Insulin; Fas ligand

Address correspondence to Khalid M. Qureshi, The Islet Research Laboratory, Worcestershire Acute Hospitals NHS Trust, Worcester, WR5 1HN, UK. Tel: 01905 760 251; Fax: 01905 760 262; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 535–542, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X536482
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Potential of Skin Fibroblasts for Application to Anterior Cruciate Ligament Tissue Engineering

Pierrot Tremblay,*† Réjean Cloutier,*† Jean Lamontagne,*† Anne-Marie Belzil,*† Anne-Marie Larkin,*† Luc Chouinard,§ Stéphane Chabaud,*† Sheila Laverty,¶ Bertrand Lussier, and Francine Goulet*†‡

*Laboratory of tissue engineering/LOEX, CHA, Hôpital de l’Enfant-Jésus, Quebec, QC, Canada
†Département de chirurgie, Université Laval, Québec, QC, Canada
‡Département de réadaptation, Université Laval, Québec, QC, Canada
§CTBR, Montreal, QC, Canada
Faculté de Médecine Vétérinaire, Département des sciences cliniques, Université de Montréal, Montreal, QC, Canada

Fibroblasts isolated from skin and from anterior cruciate ligament (ACL) secrete type I and type III collagens in vivo and in vitro. However, it is much easier and practical to obtain a small skin biopsy than an ACL sample to isolate fibroblasts for tissue engineering applications. Various tissue engineering strategies have been proposed for torn ACL replacement. We report here the results of the implantation of bioengineered ACLs (bACLs), reconstructed in vitro using a type I collagen scaffold, anchored with two porous bone plugs to allow bone–ligament–bone surgical engraftment. The bACLs were seeded with autologous living dermal fibroblasts, and grafted for 6 months in goat knee joints. Histological and ultrastructural observations ex vivo demonstrated a highly organized ligamentous structure, rich in type I collagen fibers and cells. Grafts’ vascularization and innervation were observed in all bACLs that were entirely reconstructed in vitro. Organized Sharpey’s fibers and fibrocartilage, including chondrocytes, were present at the osseous insertion sites of the grafts. They showed remodeling and matrix synthesis postimplantation. Our tissue engineering approach may eventually provide a new solution to replace torn ACL in humans.

Key words: Tissue engineering; Ligament substitute; Dermal fibroblasts; Collagen; Implant

Address correspondence to Francine Goulet, Ph.D., Laboratory of tissue engineering/LOEX, Hôpital de l’Enfant-Jésus, 1401 18e rue, Quebec, QC, Canada, G1J 1Z4. Tel: (418) 649-0252, #4344; Fax: (418) 649-5969; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it