Cell Transplantation 24(7) Abstracts

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Cell Transplantation, Vol. 24, pp. 1183-1194, 2015
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DOI: http://dx.doi.org/10.3727/096368914X681928
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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A Simple Method to Replace Islet Equivalents for Volume Quantification of Human Islets

Karthik Ramachandran,* Han-Hung Huang,† and Lisa Stehno-Bittel

*Likarda, LLC, Kansas City, KS, USA
†Physical Therapy Program, Angelo State University, Member, Texas Tech University System, San Angelo, TX, USA
‡Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS, USA

Human islets come in a variety of sizes and shapes, and the total volume of islets used for research or clinical transplants must be estimated in a manner that is simple and valid. Islet equivalent (IEQ) measurements are the standard estimate of islet volume. We published a new method (the Kansas method) for estimating rat islet volume using cell numbers that was reliable and valid. Here we modified the method for human islets. We measured the dimensions of isolated human islets showing that they are not spherical and became less so in larger islets, with an average smallest/largest diameter ratio of 0.73 in large islets and 0.85 in small islets. Human islets were individually loaded into 96-well plates, dissociated into single cells, and the total cell number per islet determined with computer-assisted cytometry. Based on the counted cell number per islet, a regression model was created to convert islet diameter to cell number with a high R2
value (0.99). Separate regression equations for male and female donors or young and old donors were not significantly different than the pooled data and did not improve the regression values. There was an inverse correlation between the cell number per IEQ and islet size. The Kansas method was validated with ATP/cell and cell viability data. Compared to the actual cell count, conventional IEQ measurements overestimated tissue volume of large islets by nearly double. Examples of differences in results obtained from the same data sets normalized to IEQ or the Kansas method included viability and insulin secretion concentrations. The implications of the error associated with the current IEQ method of volume estimation are discussed.

Key words: Islet; Islet equivalent (IEQ); Human; Insulin; ATP; Viability

Received January 4, 2014; final acceptance May 13, 2014. Online prepub date: May 15, 2014.
Address correspondence to Lisa Stehno-Bittel, Ph.D., Department of Physical Therapy and Rehabilitation Science, MS 2002, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA. Tel: +1-913-588-6733; Fax: +1-913-588-4568; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1195-1204, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X681612
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Application of Digital Image Analysis to Determine Pancreatic Islet Mass and Purity in Clinical Islet Isolation and Transplantation

Ling-jia Wang,*1 Hermann J. Kissler,†1 Xiaojun Wang,*‡ Olivia Cochet,* Adam Krzystyniak,*§ Ryosuke Misawa,* Karolina Golab,* Martin Tibudan,* Jakub Grzanka,* Omid Savari,* Dixon B. Kaufman,¶ Michael Millis,* and Piotr Witkowski*

*Department of Surgery, Division of Transplantation, University of Chicago, Chicago, IL, USA
†Department of General Visceral and Vascular Surgery, Friedrich-Schiller-University, Jena, Germany
‡Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
§Department of Clinical Immunology and Transplantology, Medical University of Gdansk and Intercollegiate Faculty of Biotechnology, University of Gdansk, Gdansk, Poland
¶Department of Surgery, Division of Transplantation, University of Wisconsin, Madison, WI, USA

Pancreatic islet mass, represented by islet equivalent (IEQ), is the most important parameter in decision making for clinical islet transplantation. To obtain IEQ, the sample of islets is routinely counted under a microscope and discarded thereafter. Islet purity, another parameter in islet processing, is routinely assessed by estimation only. In this study, we validated our digital image analysis (DIA) system by using the software of Image Pro Plus and a custom-designed Excel template to assess islet mass and purity to better comply with current good manufacturing practice (cGMP) standards. Human islet samples (60 collected from a single isolation and 24 collected from 12 isolations) were captured as calibrated digital images for the permanent record. Seven trained technicians participated in determination of IEQ and purity by the manual counting method (manual image counting, Manual I) and DIA. IEQ count showed statistically significant correlations between the Manual I and DIA in all sample comparisons (r > 0.819 and p < 0.0001). A statistically significant difference in IEQ between Manual I and DIA was not found in all sample groups (p > 0.05). In terms of purity determination, statistically significant differences between assessment and DIA measurement were found in high-purity 100-μl samples (p < 0.005) and low-purity 100-μl samples (p < 0.001) of the single isolation. In addition, islet particle number (IPN) and the IEQ/IPN ratio did not differ statistically between Manual I and DIA. In conclusion, the DIA used in this study is a reliable technique to determine IEQ and purity. Islet sample preserved as a digital image and results produced by DIA can be permanently stored for verification, technical training, and information exchange among islet centers. Therefore, DIA complies better with cGMP requirements than the manual counting method. We propose DIA as a quality control tool to supplement the established standard manual method for islet counting and purity estimation.

Key words: Digital image analysis (DIA); Islet quantification; Islet purity; Islet transplantation

Received September 10, 2012; final acceptance April 27, 2014. Online prepub date: May 6, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Ling-jia Wang, Department of Surgery, Division of Transplantation, University of Chicago, 840 South Wood Street, 502 CSB, Chicago, IL 60612, USA. Tel: +1 312 996 0530; Fax: +1 312 996 0616; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Dixon B. Kaufman, Department of Surgery, Division of Transplantation, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792, USA. E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1205-1220, 2015
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DOI: http://dx.doi.org/10.3727/096368914X679363
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Characterization of Insulin-Secreting Porcine Bone Marrow Stromal Cells Ex Vivo and Autologous Cell Therapy In Vivo

Hai Van Thi Do,* Wan Ting Loke,* Irene Kee,† Vivienne Liang,† Sebastian J. David,† Shu Uin Gan,‡ Sze Sing Lee,* Wai Har Ng,* Heng Nung Koong,§ Hock Soo Ong,¶ Kok Onn Lee,# Roy Y. Calne,‡** and Oi Lian Kon*††

*Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Republic of Singapore
SingHealth Experimental Medicine Centre, The Academia, Singapore, Republic of Singapore
‡Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore
§Department of Surgical Oncology, National Cancer Centre, Singapore, Republic of Singapore
¶Department of General Surgery, Singapore General Hospital, Singapore, Republic of Singapore
#Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore
**Department of Surgery, University of Cambridge, Cambridge, UK
††Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore

Cell therapy could potentially meet the need for pancreas and islet transplantations in diabetes mellitus that far exceeds the number of available donors. Bone marrow stromal cells are widely used in clinical trials mainly for their immunomodulatory effects with a record of safety. However, less focus has been paid to developing these cells for insulin secretion by transfection. Although murine models of diabetes have been extensively used in gene and cell therapy research, few studies have shown efficacy in large preclinical animal models. Here we report optimized conditions for ex vivo expansion and characterization of porcine bone marrow stromal cells and their permissive expression of a transfected insulin gene. Our data show that these cells resemble human bone marrow stromal cells in surface antigen expression, are homogeneous, and can be reproducibly isolated from outbred Yorkshire–Landrace pigs. Porcine bone marrow stromal cells were efficiently expanded in vitro to >1010
cells from 20 ml of bone marrow and remained karyotypically normal during expansion. These cells were electroporated with an insulin expression plasmid vector with high efficiency and viability, and secreted human insulin and C-peptide indicating appropriate processing of proinsulin. We showed that autologous insulin-secreting bone marrow stromal cells implanted and engrafted in the liver of a streptozotocin-diabetic pig that modeled type 1 diabetes resulted in partial, but significant, improvement in hyperglycemia that could not be ascribed to regeneration of endogenous b-cells. Glucose-stimulated insulin secretion in vivo from implanted cells in the treated pig was documented by a rise in serum human C-peptide levels during intravenous glucose tolerance tests. Compared to a sham-treated control pig, this resulted in significantly reduced fasting hyperglycemia, a slower rise in serum fructosamine, and prevented weight loss. Taken together, this study suggests that bone marrow stromal cells merit further development as autologous cell therapy for diabetes.

Key words: Porcine bone marrow mesenchymal stromal cells; Autologous cell therapy; Large animal model; Type 1 diabetes

Received November 19, 2013; final acceptance February 25, 2014. Online prepub date: March 24, 2014.
Address correspondence to Oi Lian Kon, Division of Medical Sciences, National Cancer Centre, Humphrey Oei Institute of Cancer Research, 11 Hospital Drive, Singapore 169610, Republic of Singapore. Tel: (+65)-6436-8307; Fax: (+65)-6372-0161; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1221-1232, 2015
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DOI: http://dx.doi.org/10.3727/096368914X681937
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Human Infrapatellar Fat Pad-Derived Stromal Cells Have More Potent Differentiation Capacity Than Other Mesenchymal Cells and Can Be Enhanced by Hyaluronan

Dah-Ching Ding,*†‡ Kun-Chi Wu,§ Hsiang-Lan Chou,‡ Wei-Ting Hung,‡ Hwan-Wun Liu,†¶ and Tang-Yuan Chu*†

*Department of Obstetrics and Gynecology, Buddhist Tzu-Chi General Hospital, Tzu Chi University, Hualien, Taiwan
†Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
‡Stem Cell Laboratory, Department of Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
§Department of Orthopedics, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan
¶Department of Occupational Medicine, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan

The microenvironment plays an important role in the homing in and differentiation of stem cells to repair injured tissue. Infrapatellar fat pad stromal cells (IFPSCs) are a promising source of such cells for the repair of articular injury-induced degeneration. This study investigated the chemotaxis of IFPSCs to chondrocytes and the effect of hyaluronan (HA) on the biological and regenerative properties of IFPSCs. The IFPSCs were obtained from patients undergoing arthroscopy and cultured via a standard 2-week culture protocol that yielded more than 10 million cells on passage 3. The results showed that the IFPSCs had a higher capacity for chondrogenic differentiation than mesenchymal cells from body fat, bone marrow, and Wharton’s jelly of the umbilical cord. The IFPSCs cultured on 25% or 50% HA showed better osteogenic and adipogenic capabilities than those without HA or with 75% HA (p < 0.001). Cultures of the IFPSCs on 25% HA had a fourfold increase in chondrogenic differentiation compared to cultures without HA, which was better than with 50% and 75% HA (p < 0.05). Cell proliferation was not affected by the presence of HA. In conclusion, IFPSCs have a strong potential for chondrogenic regeneration, which can even be augmented in a 25% HA microenvironment.

Key words: Infrapatellar fat pad; Stem cells; ChondrogenesisHyaluronan

Received July 19, 2013; final acceptance May 6, 2014. Online prepub date: May 21, 2014.
Address correspondence to Tang-Yuan Chu, M.D, Ph.D., Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan. Tel: +886-3-8561825; Fax: +886-3-8577161; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1233-1252, 2015
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DOI: http://dx.doi.org/10.3727/096368914X681603
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Characteristics and Properties of Mesenchymal Stem Cells Derived From Microfragmented Adipose Tissue

Stephana Carelli,*1 Fanuel Messaggio,*1 Alessandra Canazza,† Danuta Maria Hebda,* Filippo Caremoli,* Elisa Latorre,* Maria Grazia Grimoldi,‡ Mattia Colli,* Gaetano Bulfamante,‡ Carlo Tremolada,§ Anna Maria Di Giulio,* and Alfredo Gorio*

*Department of Health Sciences, Faculty of Medicine and Surgery, University of Milan, Milan, Italy
†Cellular Biology Laboratory, Cerebrovascular Diseases Unit, IRCCS Foundation Neurological Institute “C. Besta,” Milan, Italy
‡Department of Health Sciences, Pathology Unit, University of Milan, Milan, Italy
§Image Institute, Milan, Italy

The subcutaneous adipose tissue provides a clear advantage over other mesenchymal stem cell sources due to the ease with which it can be accessed, as well as the ease of isolating the residing stem cells. Human adipose-derived stem cells (hADSCs), localized in the stromal–vascular portion, can be isolated ex vivo using a combination of washing steps and enzymatic digestion. In this study, we report that microfragmented human lipoaspirated adipose tissue is a better stem cell source compared to normallipoaspirated tissue. The structural composition of microfragments is comparable to the original tissue. Differently, however, this procedure activates the expression of antigens, such as β-tubulin III. The hADSCs derived from microfragmented lipoaspiratetissue were systematically characterized for growth features, phenotype, and multipotent differentiation potential. They fulfill the definition of mesenchymal stem cells, although with a higher neural phenotype profile. These cells also express genes that constitute the core circuitry of self-renewal such as OCT4, SOX2, and NANOG, and neurogenic lineage genes such as NEUROD1, PAX6, and SOX3. Such findings suggest further studies by evaluating Microfrag-AT hADSC action in animal models of neurodegenerative conditions.

Key words: Mechanical fragmentation; Gene activation; Neurospheres; Neural phenotype; Fat particles; Mesenchymal stem cells

Received November 8, 2013; final acceptance April 29, 2014. Online prepub date: May 6, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Alfredo Gorio, Professor of Pharmacology and Clinical Pharmacology, Chief, Doctorate in Physiopathology, Pharmacology, and Clinical and Therapeutic Approaches to Metabolic Disorders, Department of Health Sciences, Faculty of Medicine, University of Milan, Via A. di Rudini 8, 20142 Milano, Italy. Tel: +39-02-50323032; Fax: +39-02-50323033; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1253-1263, 2015
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DOI: http://dx.doi.org/10.3727/096368914X682125
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Improvement in Spinal Cord Injury-Induced Bladder Fibrosis Using Mesenchymal Stem Cell Transplantation Into the Bladder Wall

Hong Jun Lee,*1 Jin An,*1 Seung Whan Doo,† Jae Heon Kim,† Sung Sik Choi,* Sang-Rae Lee,‡ Seung Won Park,§ Yun Seob Song,† and Seung U. Kim*¶

*Biomedical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea
†Department of Urology, Soonchunhyang University School of Medicine, Seoul, Korea
‡National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Korea
§Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea
¶Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada

Experiments on spinal cord injury (SCI) have largely focused on the transplantation of stem cells into injured spinal cords for motor recovery while neglecting to investigate bladder dysfunction. The present study was performed to investigate the effect of B10 human mesenchymal stem cells (hMSCs) directly transplanted into the bladder wall of SCI rats and to determine whether they are capable of inhibiting collagen deposition and improving cystometric parameters in SCI rats. Forty 6-week-old female Sprague–Dawley rats were divided into four groups (group 1: control, group 2: sham operated, group 3: SCI, group 4: SCI rats that received B10 cells). B10 cells were labeled with fluorescent magnetic nanoparticles (MNPs). Four weeks after the onset of SCI, MNP-labeled B10 cells were injected to the bladder wall. Serial magnetic resonance (MR) images were taken immediately after MNP-B10 injection and at 4 weeks posttransplantation. Voiding function was assessed at 4 weeks posttransplantation, and the bladder was harvested. Improvements in bladder fibrosis and bladder function were monitored by molecular MR imaging. Transplantation of B10 cells into the SCI rats markedly reduced their weights and collagen deposition. MR images showed a clear hypointensesignal induced by the MNP-labeled B10 cells at 4 weeks posttransplantation. Transplanted B10 cells were found to differentiate into smooth muscle cells. The intercontraction interval decreased, and the maximal voiding pressure increased after SCI but recovered after B10 cell transplantation. Survival of B10 cells was found at 4 weeks posttransplantation using anti-human mitochondria antibody staining and MR imaging. The transplanted B10 cells inhibited bladder fibrosis and ameliorated bladder dysfunction in the rat SCI model. MSC-based cell transplantation may be a novel therapeutic strategy for bladder dysfunction in patients with SCI.

Key words: Spinal cord injury (SCI); Bladder fibrosis; Human mesenchymal stem cells (hMSCs)

Received February 5, 2014; final acceptance June 3, 2014. Online prepub date: June 6, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Yun Seob Song, M.D., Ph.D., Department of Urology, Soonchunhyang University School of Medicine, Seoul 140-743, Korea. Tel: +82-2-709-9114; Fax: +82-2-709-9378; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Seung U. Kim, M.D., Ph.D., Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC V6T2B5, Canada. Tel: +1-604-822-7145; Fax: +1-604-822-7897; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1265-1281, 2015
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DOI: http://dx.doi.org/10.3727/096368914X682099
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Electroacupuncture Promotes the Differentiation of Transplanted Bone Marrow Mesenchymal Stem Cells Preinduced With Neurotrophin-3 and Retinoic Acid Into Oligodendrocyte-Like Cells in Demyelinated Spinal Cord of Rats

Zhou Liu,* Bing He,* Rong-Yi Zhang,* Ke Zhang,* Ying Ding,* Jing-Wen Ruan,† Eng-Ang Ling,‡ Jin-Lang Wu,§ and Yuan-Shan Zeng*¶#**

*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 Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
§Department of Electron Microscope, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
¶Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou, China
#Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, China
**Co-innovation Center of Neuroregeneration, Nantong, Jiangsu, China

Transplantation of bone marrow mesenchymal stem cells (MSCs) promotes functional recovery in multiple sclerosis (MS) patients and in a murine model of MS. However, there is only a modicum of information on differentiation of grafted MSCs into oligodendrocyte-like cells in MS. The purpose of this study was to transplant neurotrophin-3 (NT-3) and retinoic acid (RA) preinduced MSCs (NR-MSCs) into a demyelinated spinal cord induced by ethidium bromide and to investigate whether EA treatment could promote NT-3 secretion in the demyelinated spinal cord. We also sought to determine whether increased NT-3 could further enhance NRMSCs overexpressing the tyrosine receptor kinase C (TrkC) to differentiate into more oligodendrocyte-like cells, resulting in increased remyelination and nerve conduction in the spinal cord. Our results showed that NT-3 and RA increased transcription of TrkC mRNA in cultured MSCs. EA increased NT-3 levels and promoted differentiation of oligodendrocyte-like cells from grafted NR-MSCs in the demyelinated spinal cord. There was evidence of myelin formation by grafted NR-MSCs. In addition, NR-MSC transplantation combined with EA treatment (the NR-MSCs + EA group) reduced demyelination and promotedremyelination. Furthermore, the conduction of cortical motor-evoked potentials has improved compared to controls. Together, our data suggest that preinduced MSC transplantation combined with EA treatment not only increased MSC differentiation into oligodendrocyte-like cells forming myelin sheaths, but also promoted remyelination and functional improvement of nerve conduction in the demyelinated spinal cord.

Key words: Multiple sclerosis (MS); Bone marrow mesenchymal stem cells (MSCs); Electroacupuncture; Tyrosine receptor kinase C (TrkC); Differentiation

Received September 29, 2013; final acceptance May 21, 2014. Online prepub date: May 22, 2014.
Address correspondence to Yuan-Shan Zeng, M.D., Ph.D., Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, 74# Zhongshan 2nd Road, Guangzhou 510080, China. Tel: +86-20-87332698; Fax: +86-20-87332698; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1283-1297, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X682134
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Bone Marrow Stromal Cells Combined With a Honeycomb Collagen Sponge Facilitate Neurite Elongation In Vitro and Neural Restoration in the Hemisected Rat Spinal Cord

Madoka Onuma-Ukegawa,* Kush Bhatt,† Takashi Hirai,* Hidetoshi Kaburagi,* Shinichi Sotome,‡ Yoshiaki Wakabayashi,* Shizuko Ichinose,§ Kenichi Shinomiya,* Atsushi Okawa,* and MitsuhiroEnomoto

*Department of Orthopaedic and Spinal Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
†Imperial College, Tokyo Medical and Dental University Exchange Program, Tokyo, Japan
‡Department of Orthopaedic Research and Development, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
§Instrumental Analysis Research Center, Tokyo Medical and Dental University, Tokyo, Japan
¶Hyperbaric Medical Center, Tokyo Medical and Dental University, Tokyo, Japan

In the last decade, researchers and clinicians have reported that transplantation of bone marrow stromal cells (BMSCs) promotes functional recovery after brain or spinal cord injury (SCI). However, an appropriate scaffold designed for the injured spinal cord is needed to enhance the survival of transplanted BMSCs and to promote nerve regeneration. We previously tested a honeycomb collagen sponge (HC), which when applied to the transected spinal cord allowed bridging of the gap with nerve fibers. In this study, we examined whether the HC implant combined with rat BMSCs increases nerve regeneration in vitro and enhances functional recovery in vivo. We first evaluated the neurite outgrowth of rat dorsal root ganglion (DRG) explants cultured on HC with or without BMSCs in vitro. Regeneration of neurites from the DRGs was increased by BMSCs combined with HC scaffolds. In the in vivo study, 3-mm-long HC scaffolds with or without BMSCs were implanted into the hemisected rat thoracic spinal cord. Four weeks after the procedure, rats implanted with HC scaffolds containing BMSCs displayed better motor and sensory recovery than those implanted with HC scaffolds only. Histologically, more CGRP-positive sensory fibers at the implanted site and 5-HT-positive serotonergic fibers contralateral to the implanted site were observed in spinal cords receiving BMSCs. Furthermore, more rubrospinal neurons projected distally to the HC implant containing BMSCs. Our study indicates that the application of BMSCs in a HC scaffold in the injured spinal cord directly promoted sensory nerve and rubrospinal tract regeneration, thus resulting in functional recovery.

Key words: Spinal cord injury (SCI); Bone marrow stromal cells (BMSCs); Scaffold; Transplantation; Regeneration

Received September 4, 2013; final acceptance June 4, 2014. Online prepub date: June 6, 2014.
Address correspondence to Mitsuhiro Enomoto, Department of Orthopaedic Surgery and Hyperbaric Medical Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan. Tel: +81-3-5803-5279; Fax: +81-3-5803-5281; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1299-1311, 2015
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DOI: http://dx.doi.org/10.3727/096368914X681711
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Control of the Survival and Growth of Human Glioblastoma Grafted Into the Spinal Cord of Mice by Taking Advantage of Immunorejection

Go Itakura,*† Yoshiomi Kobayashi,* Soraya Nishimura,*† Hiroki Iwai,*† Morito Takano,* Akio Iwanami,* Yoshiaki Toyama,* Hideyuki Okano,† and Masaya Nakamura*

*Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan
†Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan

Recent studies have demonstrated that transplantation of induced pluripotent stem cell-derived neurospheres can promote functional recovery after spinal cord injury in rodents, as well as in nonhuman primates. However, the potential tumorigenicity of the transplanted cells remains a matter of apprehension prior to clinical applications. As a first step to overcome this concern, this study established a glioblastoma multiforme xenograft model mouse. The feasibility of controlling immune suppression to ablate the grafted cells was then investigated. The human glioblastoma multiforme cell line U251 MG was transplanted into the intact spinal cords of immunodeficient NOD/SCID mice or into those of immunocompetent C57BL/6J H-2kb mice treated with or withoutimmunosuppressants [FK506 plus anticluster of differentiation (CD) 4 antibody (Ab), or FK506 alone]. In vivo bioluminescent imaging was used to evaluate the chronological survival of the transplanted cells. The graft survival rate was 100% (n = 9/9) in NOD/SCID mice, 0% (n = 6/6) in C57BL/6J mice without immunosuppressant treatment, and 100% (n = 37/37) in C57BL6/J mice with immunosuppressant treatment. After confirming the growth of the grafted cells in the C57/BL6J mice treated withimmunosuppressants, immune suppression was discontinued. The grafted cells were subsequently rejected within 3 days in C57BL/6J mice treated with FK506 alone, as opposed to 26 days in C57BL/6J mice treated with FK506 plus anti-CD4 Ab. Histological evaluation confirmed the ablation of the grafted cells. Although this work describes a xenograft setting, the results suggest that this immunomodulatory strategy could provide a safety lock against tumor formation stemming from transplanted cells.

Key words: Spinal cord injury; Cell transplantation; Spinal glioblastoma; Xenograft model

Received October 12, 2013; final acceptance May 6, 2014. Online prepub date: May 9, 2014.
Address correspondence to Masaya Nakamura, Department of Orthopaedic Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Tel: +81-3-5363-3812; Fax: +81-3-3353-6597; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Hideyuki Okano, Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Tel: +81-3-5363-3747; Fax: +81-3-3357-5445; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1313-1328, 2015
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DOI: http://dx.doi.org/10.3727/096368914X681739
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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CXCR4 Antagonist TG-0054 Mobilizes Mesenchymal Stem Cells, Attenuates Inflammation, and Preserves Cardiac Systolic Function in a Porcine Model of Myocardial Infarction

Wan-Tseng Hsu,*† Hsiang-Yiang Jui,‡ Ying-Huey Huang,§ Mao-Yuan M. Su,¶ Yen-Wen Wu,‡ Wen-Yih I. Tseng,# Ming-Chu Hsu,§ Bor-Luen Chiang,* Kenneth K. Wu,†** and Chii-Ming Lee†‡

*Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
†Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan
‡Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
§TaiGen Biotechnology Co., Ltd., Taipei, Taiwan
¶Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
#Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan
**Metabolomic Medicine Research Center, China Medical University, Taichung, Taiwan

Interaction between chemokine stromal cell-derived factor 1 and the CXC chemokine receptor 4 (CXCR4) governs the sequestration and mobilization of bone marrow stem cells. We investigated the therapeutic potential of TG-0054, a novel CXCR4 antagonist, in attenuating cardiac dysfunction after myocardial infarction (MI). In miniature pigs (minipigs), TG-0054 mobilized CD34+CXCR4+, CD133+CXCR4+, and CD271+CXCR4+
cells into peripheral circulation. After isolation and expansion, TG-0054-mobilized CD271+ cells were proved to be mesenchymal stem cells (designated CD271-MSCs) since they had trilineage differentiation potential, surface markers of MSCs, and immunosuppressive effects on allogeneic lymphocyte proliferation. MI was induced in 22 minipigs using balloon occlusion of the left anterior descending coronary artery, followed by intravenous injections of 2.85 mg/kg of TG-0054 or saline at 3 days and 7 days post-MI. Serial MRI analyses revealed that TG-0054 treatment prevented left ventricular (LV) dysfunction at 12 weeks after MI (change of LV ejection fraction from baseline, −1.0 ± 6.2% in the TG-0054 group versus −7.9 ± 5.8% in the controls). The preserved cardiac function was accompanied by a significant decrease in the myocardial expression of TNF-α, IL-1β, and IL-6 at 7 days post-MI. Moreover, the plasma levels of TNF-α, IL-1β, and IL-6 were persistently suppressed by the TG-0054 treatment. Infusion of TG-0054-mobilized CD271-MSCs reduced both myocardial and plasma cytokine levels in a pattern, which is temporally correlated with TG-0054 treatment. This study demonstrated that TG-0054 improves the impaired LV contractility following MI, at least in part, by mobilizing MSCs to attenuate the postinfarctioninflammation. This insight may facilitate exploring novel stem cell-based therapy for treating post-MI heart failure.

Key words: Myocardial infarction (MI); CXC chemokine receptor 4 (CXCR4) antagonist; Mesenchymal stem cells (MSCs); Inflammation; Immunomodulation

Received November 27, 2013; final acceptance May 9, 2014. Online prepub date: May 12, 2014.
Address correspondence to Chii-Ming Lee, M.D., Ph.D., Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei City 10002, Taiwan. Tel: +886 972651087; Fax: +886 2 23934176; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1329-1341, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X681748
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Modulation of FasFas Ligand Interaction Rehabilitates Hypoxia-Induced Apoptosis of Mesenchymal Stem Cells in Ischemic Myocardium Niche

Onju Ham,*1 Se-Yeon Lee,*1 Byeong-Wook Song,†‡ Min-Ji Cha,†‡ Chang Youn Lee,§ Jun-Hee Park,§ Il-Kwon Kim,†‡ Jiyun Lee,* Hyang-Hee Seo,* Min-Ji Seung,* Eunhyun Choi,†‡ Yangsoo Jang,*¶ and Ki-Chul Hwang†‡

*Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
†Institute of Catholic Integrative Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Incheon, Republic of Korea
‡Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-siGangwon-do, Republic of Korea
§Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul, Republic of Korea
¶Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea

Mesenchymal stem cells (MSCs) have the potential to repair and regenerate ischemic heart tissue; however, the poor viability of transplanted MSCs in the ischemic region is a major obstacle to their therapeutic use. This cell death is caused by Fas and Fasligand (FasL) interactions under harsh conditions. To investigate improving the survival and therapeutic effects of MSCs, we focused our research on FasFasL-mediated cell death. In this study, we found that the poor viability of transplanted MSCs was caused by FasFasL interactions between host ischemic myocardial cells and implanted MSCs. In addition, we found that increased Fas expression and the corresponding decrease of cell survival were in close relation to hypoxic MSCs treated with FasL and H2O2. When MSCs were treated with a recombinant Fas/Fc chimera (Fas/Fc) inhibiting FasFasL interactions, the expressions of proapoptotic proteins including caspase-8, caspase-3, Bax, and cytochrome-c were attenuated, and the survival of MSCs was recovered. In ischemia–reperfusion injury models, the interaction between FasL in ischemic heart and Fas in implanted MSCs caused a loss of transplanted MSCs, whereas the inhibition of this interaction by Fas/Fc treatment improved cell survival and restored heart function. Thus, our study suggests that FasFasL interactions are responsible for activating cell death signaling in implanted stem cells and could be a potential target for improving therapeutic efficacy of stem cells in treating ischemic heart diseases.

Key words: FasFas ligand (FasL); Ishcemic heart; Transplantation; Mesenchymal stem cells (MSCs)

Received November 26, 2013; final acceptance May 9, 2014. Online prepub date: May 12, 2014
1These authors provided equal contribution to this work.
Address correspondence to Ki-Chul Hwang, Ph.D., Institute of Catholic Integrative Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Incheon 403-720, Republic of Korea. Tel: +82-32-290-3883; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1343-1361, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672064
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Strategies to Enhance the Efficiency of Endothelial Progenitor Cell Therapy by Ephrin B2 Pretreatment and Coadministration with Smooth Muscle Progenitor Cells on Vascular Function During the Wound-Healing Process in Irradiated or Nonirradiated Condition

Philippe Foubert,* Claire Squiban,† Valérie Holler,† Valérie Buard,† Carole Dean,* Bernard I. Levy,* Marc Benderitter,† Jean Sébastien Silvestre,‡ Gérard Tobelem,* and Radia Tamarat

*IVS Institut des Vaisseaux et du Sang, Paris, France
†Institute of Radioprotection and Nuclear Safety (IRSN), DRPH/SRBE/LRTE, France FAR, France
‡INSERM 970, Cardiovascular Research Center, Paris, France

Endothelial progenitor cell (EPC) transplantation has beneficial effects for therapeutic neovascularization. We therefore assessed the effect of a therapeutic strategy based on EPC administration in the healing of radiation-induced damage. To improve cell therapy for clinical use, we used pretreatment with ephrin B2-Fc (Eph-B2-Fc) and/or coadministration with smooth muscle progenitor cells. At day 3, EPCs promoted dermal wound healing in both nonirradiated and irradiated mice by 1.2- and 1.15-fold, respectively, compared with animals injected with phosphate-buffered saline. In addition, EPCs also improved skin–blood perfusion and capillary density in both irradiated and nonirradiated mice compared with PBS-injected animals. We also demonstrated that activation with Eph-B2-Fc increased wound closure by 1.6-fold compared with unstimulated EPCs in nonirradiated mice. Interestingly, the beneficial effect of Eph-B2-Fc was abolished in irradiated animals. In addition, we found that Eph-B2-Fc stimulation did not improve EPC-induced vascular permeability or adhesiveness compared to unstimulated EPCs. We hypothesized that this effect was due to high oxidative stress during irradiation, leading to inhibition of EPCs’ beneficial effect on vascular function. In this line, we demonstrated that, in irradiated conditions, N-acetyl-
L-cysteine treatment restored the beneficial effect of EPC stimulation with Eph-B2-Fc in the wound healing process. In conclusion, stimulation by Eph-B2-Fc improved the beneficial effect of EPCs in physiological conditions and irradiated conditions only in association with antioxidant treatment. Additionally, cotherapy was beneficial in pathological conditions.

Key words: Wound healing; Endothelial progenitors cells (EPCs); Ephrin B; Progenitors of smooth muscle cells; Radiation

Received October 22, 2012; final acceptance August 29, 2013. Online prepub date: September 10, 2013.
Address correspondence to Dr. Radia Tamarat, Institute of Radioprotection and Nuclear Safety (IRSN), DRPH/SRBE/LRTE, BP 17, 92262 Fontenay-aux-Roses Cedex, France. Tel: +33 1 58 35 82 80; Fax: +33 1 58 35 84 67; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1363-1377, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X681720
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Endothelial Progenitor Cells Derived From Wharton’s Jelly of Human Umbilical Cord Attenuate Ischemic Acute Kidney Injury by Increasing Vascularization and Decreasing Apoptosis, Inflammation, and Fibrosis

Chan-Jung Liang,*† Wen-Ching Shen,* Fu-Bin Chang,* Vin-Cent Wu,‡ Shu-Huei Wang,* Guang-Huar Young,§ Jaw-Shiun Tsai,¶ Ying-Chin Tseng,# Yu-Sen Peng,** and Yuh-Lien Chen*

*Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
†Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
‡Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
§Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
¶Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
#Department of Obstetrics and Gynecology, Hsinchu Cathay General Hospital, Hsinchu, Taiwan
**Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan

Ischemia–reperfusion (I/R) injury to the kidney, a major cause of acute renal failure in humans, is associated with a high mortality, and the development of a new therapeutic strategy is therefore highly desirable. In this study, we examined the therapeutic potential of implantation of endothelial progenitor cells (EPCs) isolated from Wharton’s jelly of human umbilical cords in the treatment of renal I/R injury in mice. To visualize the localization of the transplanted EPCs, the cells were labeled with Q-tracker before injection into the renal capsule. Mice with renal I/R injury showed a significant increase in blood urea nitrogen and creatinine levels, and these effects were decreased by EPC transplantation. The kidney injury score in the mice with I/R injury was also significantly decreased by EPC transplantation. EPC transplantation increased the microvascular density, and some of the EPCs surrounded and were incorporated into microvessels. In addition, EPC transplantation inhibited the I/R-induced cell apoptosis of endothelial, glomerular, and renal tubular cells, as demonstrated by TUNEL staining, and significantly reduced reactive oxygen species production and the expression of the inflammatory chemokines macrophage inflammatory protein-2 and keratinocyte-derived cytokine, as shown by immunostaining and ELISA. Moreover, EPC transplantation reduced I/R-induced fibrosis, as demonstrated by immunostaining for S100A4, a fibroblast marker, and by Jones silver staining. To our knowledge, this is the first report that transplantation of EPCs from Wharton’s jelly of human umbilical cords might provide a novel therapy for ischemic acute kidney injury by promoting angiogenesis and inhibiting apoptosis, inflammation, and fibrosis.

Key words: Endothelial progenitor cells (EPCs); Acute kidney injury (AKI); Ischemia; Angiogenesis; Apoptosis

Received December 13, 2013; final acceptance May 8, 2014. Online prepub date: May 9, 2014.
Address correspondence to Dr. Yuh-Lien Chen, Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Ren-Ai Rd, Taipei 100, Taiwan. Tel: +(886)-2-23123456-88176; Fax: +(886)-2-33931713; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  orDr. Yu-Sen Peng, Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, No. 21, Nan-Ya South Road, Section 2, Banciao District, New Taipei City, Taiwan. E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1379-1393, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X681586
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Superior Potential of CD34-Positive Cells Compared to Total Mononuclear Cells for Healing of Nonunion Following Bone Fracture

Tomoaki Fukui,*†1 Yutaka Mifune,*†1 Tomoyuki Matsumoto,*† Taro Shoji,*† Yohei Kawakami,*† Atsuhiko Kawamoto,* Masaaki Ii,‡ Hiroshi Akimaru,* Tomoya Kuroda,*† Miki Horii,* AyumiYokoyama,* Cantas Alev,* Ryosuke Kuroda,† Masahiro Kurosaka,† and Takayuki Asahara

*Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation, Kobe, Hyogo, Japan
†Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
‡Group of Translational Stem Cell Research, Department of Pharmacology, Osaka Medical College, Takatsuki, Osaka, Japan
§Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan

We recently demonstrated that the local transplantation of human peripheral blood (PB) CD34+
cells, an endothelial/hematopoietic progenitor cell-rich population, contributes to fracture repair via vasculogenesis/angiogenesis and osteogenesis. Human PB mononuclear cells (MNCs) are also considered a potential cell fraction for neovascularization. We have previously shown the feasibility of human PB MNCs to enhance fracture healing. However, there is no report directly comparing the efficacy for fracture repair between CD34+ cells and MNCs. In addition, an unhealing fracture model, which does not accurately resemble a clinical setting, was used in our previous studies. To overcome these issues, we compared the capacity of human granulocyte colony-stimulating factor-mobilized PB (GM-PB) CD34+ cells and human GM-PB MNCs in a nonunion model, which more closely resembles a clinical setting. First, the effect of local transplantation of 1 × 105 GM-PB CD34+ cells (CD34+ group), 1 × 107 GM-PB MNCs (containing approximately 1 × 105 GM-PB CD34+ cells) (MNC group), and phosphate-buffered saline (PBS) (PBS group) on nonunion healing was compared. Similar augmentation of blood flow recovery at perinonunion sites was observed in the CD34+ and MNC groups. Meanwhile, a superior effect on nonunion repair was revealed by radiological, histological, and functional assessment in the CD34+ group compared with the other groups. Moreover, through in vivo and in vitro experiments, excessive inflammation induced by GM-PB MNCs was confirmed and believed to be one of the mechanisms underlying this potency difference. These results strongly suggest that local transplantation of GM-PB CD34+ cells is a practical and effective strategy for treatment of nonunion after fracture.

Key words: Bone fracture; CD34+
cells; Cell transplantation; Mononuclear cells (MNCs); Nonunion

Received August 14, 2011; final acceptance April 19, 2014. Online prepub date: May 2, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Takayuki Asahara, M.D., Ph.D., Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation, 2-2 Minatojimaminami-machi, Chuo-ku, Kobe 650-0047, Japan. Tel: +81-78-304-5772; Fax: +81-78-304-5263; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1395-1404, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X682116
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Involvement of Caveolin-1 in CD83 Internalization in Mouse Dendritic Cells

Yuejing Yang,* Zhongcheng Xin,† Jingjia Chu,‡ Na Li,‡ and Tao Sun‡§

*The 2nd Affiliated Hospital, Zhengzhou University, Zhengzhou, China
Andrology Center, Urology Department, Peking University First Hospital, Peking University, Beijing, China
‡Western Science Centre, Western University, London, Ontario, Canada
§Critical Illness Research, Lawson Health Research Institute, Western University, London, Ontario, Canada

To become potent T-cell stimulators, DCs need to mature. Treatment with soluble CD83 (sCD83) induces immune tolerance and protects against transplant rejection by maintaining dendritic cells in an immature, tolerogenic state. Until now, the mechanism through which sCD83 keeps DCs immature has not been investigated. The internalizing pathway of CD83 was screened by Western blot, and the direct interactions between internalized proteins were verified through coimmunoprecipitation (co-IP) and transmission electron microscopy (TEM). CD83 plasma membrane levels were detected by Western blot using a plasma membrane protein extraction protocol. The changes in CD83 surface levels in DCs were detected by flow cytometry. Caveolin-1 function was detected in a kidney transplant model. In this study, we demonstrated that caveolin-1 could affect CD83 level during endocytosis in mouse DCs. Caveolin-1 coprecipitates with CD83, as demonstrated by co-IP analysis. TEM morphometric analysis of the entire CD83 distribution associated with internalized caveolin-1 demonstrated a significant interaction in cellular vesicles. sCD83 reduces endogenous CD83 plasma membrane levels, and caveolin-1 knockdown reverts CD83 levels in plasma membrane.sCD83 treatment decreases CD83 surface levels in DCs. siRNA to caveolin-1 in DCs inhibits this effect of sCD83. The effects of sCD83-treated DCs were proved in CD1 mice. Knocking down caveolin-1 in DCs obstructs the effects of sCD83 on kidney transplant. In conclusion, our data indicated that a caveolin-dependent endocytic pathway is involved in CD83 internalization in DCs and that caveolin-1 is involved in the activity of DCs.

Key words: CD83; Caveolin; Dendritic cells; Endocytosis; Transplantation

Received January 17, 2014; final acceptance May 30, 2014. Online prepub date: June 3, 2014.
Address correspondence to Tao Sun, M.D., Ph.D., Critical Illness Research, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada N6A 4G5. Tel: +1 226 973 5339; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it