Cell Transplantation 23(3) Abstracts

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Cell Transplantation, Vol. 23, pp. 263-272, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368912X662372
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

In Vitro Maturation of Viable Islets From Partially Digested Young Pig Pancreas

Morgan Lamb,*† Kelly Laugenour,* Ouwen Liang,* Michael Alexander,*† Clarence E. Foster III,* and Jonathan R. T. Lakey*†‡

*Department of Surgery, University of California Irvine, Orange, CA, USA
†Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA
‡Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA

Isolation of islets from market-sized pigs is costly, with considerable islet losses from fragmentation occurring during isolation and tissue culture. Fetal and neonatal pigs yield insulin unresponsive islet-like cell clusters that become glucose-responsive after extended periods of time. Both issues impact clinical applicability and commercial scale-up. We have focused our efforts on a cost-effective scalable method of isolating viable insulin-responsive islets. Young Yorkshire pigs (mean age 20 days, range 4–30 days) underwent rapid pancreatectomy (<5 min) and partial digestion using low-dose collagenase, followed by in vitro culture at 37°C and 5% CO2 for up to 14 days. Islet viability was assessed using FDA/PI or Newport Green, and function was assessed using a glucose-stimulated insulin release (GSIR) assay. Islet yield was performed using enumeration of dithizone-stained aliquots. The young porcine (YP) islet yield at dissociation was 12.6 ± 2.1 × 103 IEQ (mean ± SEM) per organ and increased to 33.3 ± 6.4 × 103 IEQ after 7 days of in vitro culture. Viability was 97.3 ± 7% at dissociation and remained over 90% viable after 11 days in tissue culture (n = ns). Glucose responsiveness increased throughout maturation in culture. The stimulation index (SI) of the islets increased from 1.7 ± 2 on culture day 3 to 2.58 ± 0.5 on culture day 7. These results suggest that this method is both efficient and scalable for isolating and maturing insulin-responsive porcine islets in culture.

Key Words: Diabetes mellitus; Islet transplantation; Xenotransplantation; Porcine islets

Received September 7, 2012; final acceptance December 21, 2012. Online prepub date: February 7, 2013.
Address correspondence to Jonathan R. T. Lakey, Ph.D., Associate Professor of Surgery and Biomedical Engineering, Department of Surgery, University of California Irvine, 333 The City Blvd. West, Suite 700, Orange, CA 92868, USA. Tel: +1 (714) 456-5386; Fax: +1 (714) 938-0324; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 273-283, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368912X661364
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Potential of Endothelial Colony-Forming Cells to Improve Early Graft Loss After Intraportal Islet Transplantation

Hye Seung Jung,*† Min Joo Kim,* Shin Hee Hong,† Ye Jin Lee,† Shiane Kang,* Hakmo Lee,† Sung Soo Chung,† Joong Shin Park,‡ and Kyong Soo Park*†

*Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
†Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea
‡Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea

Early graft loss in islet transplantation means that a large amount of donor islets is required. Endothelial cells and endothelial colony-forming cells (ECFCs) have been reported to improve instant blood-mediated inflammatory reaction (IBMIR) in vitro. In this study, we examined if ECFC-coated porcine islets would prevent early graft loss in vivo. Human ECFCs were prepared from cord blood and cocultured with islets to make composite grafts. Diabetic nude mice underwent intraportal transplantation. Blood glucose levels were monitored, and morphological examination of the grafts along with analysis of the components of IBMIR and inflammatory reaction were performed with the liver tissues. The ECFC-coated islets significantly decreased blood glucose levels immediately after transplantation compared to the uncoated islets. Composite ECFC islet grafts were observed in the liver sections, associated with a more insulin+ area compared to that of the uncoated group within 48 h after transplantation. Deposition of CD41a, C5b-9, and CD11b+ cells was also decreased in the ECFC-coated group. Expression of porcine HMGB1 and mouse TNF-α was increased in the transplantated groups compared to the sham operation group, with a trend of a decreasing trend across the uncoated group, the ECFC-coated group, and the sham group. We demonstrated that the composite ECFC porcine islets transplanted into the portal vein of nude mice improved early graft loss and IBMIR in vivo.

Key words: Islet transplantation (ITx); Instant blood-mediated inflammatory reaction (IBMIR); Endothelial colony-forming cells (ECFCs); Endothelial progenitor cell; Early graft loss; High-mobility group box 1 (HMGB1)

Received December 27, 2011; final acceptance December 6, 2012. Online prepub date: January 2, 2013.
Address correspondence to Kyong Soo Park, M.D., Ph.D., Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Republic Korea. Tel: +82-2-2072-1789; Fax: +82-2-3676-8309; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 285-301, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368912X663541
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Transplantation of Cyclic Stretched Fibroblasts Accelerates the Wound-Healing Process in Streptozotocin-Induced Diabetic Mice

Eunkyung Lee,*1 Do Yeon Kim,*†1 Eunkyung Chung,* Eun Ah Lee,* Ki-Sook Park,‡§2 and Youngsook Son*§2

*Department of Genetic Engineering, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yongin, Korea
†St. Peter’s Hospital and R&D Center, Cell & Bio, Inc., Seoul, Korea
‡East-West Medical Research Institute, Kyung Hee University, Seoul, Korea
§College of Medicine, Kyung Hee University, Seoul, Korea

Mechanical stimulation is a known modulator of survival and proliferation for many cells, including endothelial cells, smooth muscle cells, and bone marrow-derived mesenchymal stem cells. In this study, we found that mechanical strain prevents apoptosis and increases the adhesive ability of dermal fibroblasts in vitro and thus confers the survival advantage in vivo after transplantation of fibroblasts into the full-thickness wound of diabetic mice. Cyclic stretch at a frequency of 0.5 Hz and maximum elongation of 20% stimulates cellular survival mediated by the activation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and the serine/threonine kinase Akt (AKT). Stretching of the fibroblasts increases the synthesis of extracellular matrix proteins and the formation of denser focal adhesion structures, both of which are required for fibroblast adhesion. The stretched fibroblasts also upregulate the expression of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α), which enhanced wound healing in vivo. Indeed, preconditioning with mechanical stretch allows better survival of the transplanted fibroblasts, when compared to unstretched control cells, in the wound environment of mice with streptozotocin-induced diabetes and thus accelerates the wound-healing process in these mice.

Keywords: Cell survival; Cyclic stretch; Mechanical stimulus; Angiogenesis; Wound healing

Received July 19, 2012; final acceptance January 4, 2013. Online prepub date: February 4, 2013.
1These authors provided equal contribution to this work and are co-first authors.
2These authors provided equal contribution to this work as co-corresponding authors.
Address correspondence to Youngsook Son, Ph.D., Department of Genetic Engineering, Kyung Hee University, Seocheondong, Kiheung-gu, Yongin, 446-701, Republic of Korea. Tel: +82-31-201-3822; Fax: +82-31-206-3829; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Ki-Sook Park, Ph.D., East-West Medical Research Institute/College of Medicine, 25 Kyungheedae-ro, Dongdaemun-gu, Seoul, 130-701, Republic of Korea. Tel:+82-2-958-9368; Fax:+82-2-958-9083; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 303-317, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X663569
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Human Cord Blood-Derived Unrestricted Somatic Stem Cells Promote Wound Healing and Have Therapeutic Potential for Patients With Recessive Dystrophic Epidermolysis Bullosa

Yanling Liao,* Munenari Itoh,† Albert Yang,* Hongwen Zhu,* Samantha Roberts,* Alexandra M. Highet,* Shaun Latshaw,* Kelly Mitchell,* Carmella van de Ven,* Angela Christiano,‡ and Mitchell S. Cairo*§¶#**

*Department of Pediatrics, New York Medical College, Valhalla, NY, USA
†Department of Dermatology, Jikei University School of Medicine, Tokyo, Japan
‡Department of Dermatology, Columbia University Medical Center, New York, NY, USA
§Department of Medicine, New York Medical College, Valhalla, NY, USA
¶Department of Pathology, New York Medical College, Valhalla, NY, USA
#Immunology and Microbiology, New York Medical College, Valhalla, NY, USA
**Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA

Human umbilical cord blood (CB)-derived unrestricted somatic stem cells (USSCs) have previously been demonstrated to have a broad differentiation potential and regenerative beneficial effects when administered in animal models of multiple degenerative diseases. Here we demonstrated that USSCs could be induced to express genes that hallmark keratinocyte differentiation. We also demonstrated that USSCs express type VII collagen (C7), a protein that is absent or defective in patients with an inherited skin disease, recessive dystrophic epidermolysis bullosa (RDEB). In mice with full-thickness excisional wounds, a single intradermal injection of USSCs at a 1-cm distance to the wound edge resulted in significantly accelerated wound healing. USSC-treated wounds displayed a higher density of CD31+ cells, and the wounds healed with a significant increase in skin appendages. These beneficial effects were demonstrated without apparent differentiation of the injected USSCs into keratinocytes or endothelial cells. In vivo bioluminescent imaging (BLI) revealed specific migration of USSCs modified with a luciferase reporter gene, from a distant intradermal injection site to the wound, as well as following systemic injection of USSCs. These data suggest that CB-derived USSCs could significantly contribute to wound repair and be potentially used in cell therapy for patients with RDEB.

Key words: Skin; Stem cell transplantation; Human stem cells; Dermatology; Stem cells; Transplantation

Received August 12, 2012; final acceptance January 11, 2013. Online prepub date: February 4, 2013.
Address correspondence to Mitchell S. Cairo, Associate Chairman, Department of Pediatrics, Professor of Pediatrics, Medicine, Pathology, Microbiology & Immunology and Cell Biology & Anatomy Maria Fareri Children’s Hospital at Westchester Medical Center, New York Medical College Munger Pavilion, Room 110A, Valhalla, NY 10595, USA. Tel: +1-914-594-3650; Fax: +1-914-594-3803; Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 319-328, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368912X661409
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Human Amnion Epithelial Cells Mediate Lung Repair by Directly Modulating Macrophage Recruitment and Polarization

Jean L. Tan,* Siow Teng Chan,* Euan M. Wallace,*† and Rebecca Lim*†

*The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia
†Department of Obstetrics and Gynecology, Monash Medical Centre, Clayton, Victoria, Australia

Human amnion epithelial cells (hAECs) have been shown to modulate inflammation and restore normal lung structure and respiratory function following bleomycin challenge in immune-competent mice. These effects are exerted despite a lack of significant engraftment of hAECs, suggesting that immunomodulatory effect mechanisms are at play. In this study, using the bleomycin model of injury, we explored the interactions between hAECs and macrophages. We administered 4 million hAECs intraperitoneally to C57Bl6 mice 24 h following a bleomycin challenge. Using FACS analysis and qPCR, we showed that hAEC administration significantly reduced macrophage infiltration into the lungs and that the majority of the pulmonary macrophages were of the M2 phenotype. Using bone marrow-derived macrophages, we then showed that hAEC-conditioned media could alter macrophage polarization, migration, and phagocytosis, without affecting macrophage survival or proliferation in vitro. This study provides the first evidence that hAECs directly influence macrophage behavior in a proreparative manner and suggests that hAECs are able to mediate these effects independently of other immune cell types.

Key words: Immune modulation; Macrophages; Lung inflammation; Human amnion epithelial cells (hAECs); Placenta

Received June 5, 2012; final acceptance December 7, 2012. Online prepub date: January 2, 2013.
Address correspondence to Dr. Rebecca Lim, The Ritchie Centre, Monash Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia. Tel: +613-95947410; Fax: +613-95945003; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 329-343, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X663569
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Ex Vivo Magnetic Resonance Imaging of Transplanted Hepatocytes in a Rat Model of Acute Liver Failure

Juliana Puppi,* Michel Modo,† Anil Dhawan,*‡ Sharon C. Lehec,* Ragai R. Mitry,*1 and Robin D. Hughes*1

*Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, London, UK
†Department of Neuroscience, Institute of Psychiatry, King’s College London, London, UK
‡Paediatric Liver Centre, King’s College Hospital, London, UK

Hepatocyte transplantation is being evaluated as an alternative to liver transplantation. However, the fate of hepatocytes after transplantation is not well defined. The aims of the study were to improve hepatocyte labeling in vitro using superparamagnetic iron oxide nanoparticles (SPIOs) and to perform in vivo experiments on tracking labeled cells by magnetic resonance imaging (MRI). Human and rat hepatocytes were labeled in vitro for 16 h with clinically approved SPIOs (12.5 μg Fe/ml) and protamine sulfate (3 μg/ml) as a transfection agent. Increased cellular iron uptake was obtained, and cell viability and function were shown not to be affected by labeling. Labeled cells (2,000/μl) could be detected on T2-weighted images in vitro using a 7T MR scanner. In a rat model of acute liver failure (ALF), female recipients received intrasplenic transplantation of 2 × 107 male rat hepatocytes 28–30 h after intraperitoneal injection of D-galactosamine (1.2 g/kg). There were four groups (n = 4 each): vehicle injection, injection of freshly isolated cells labeled with CM-DiI, injection of cultured cells labeled with CM-DiI, and injection of cultured cells labeled with both SPIOs and CM-DiI. Ex vivo T2*-weighted gradientecho images at 7T MRI were acquired at day 7 post-ALF induction. Six days after transplantation, SPIOs were detected in the rat liver as a decrease in the MRI signal intensity in the surviving animals. Histologically, most of the SPIOs were located in Kupffer cells, indicating clearance of labeled hepatocytes. Furthermore, labeled cells could not be detected in the liver by the fluorescent dye or by PCR for the Y-chromosome (Sry-2 gene). In conclusion, optimum conditions to label human hepatocytes with SPIOs were established and did not affect cell viability or metabolic function and were sufficient for in vitro MRI detection. However, the clearance of hepatocytes after transplantation limits the value of MRI for assessing long-term hepatocyte engraftment.

Key words: Acute liver failure; Hepatocyte transplantation; Cell labeling; Superparamagnetic iron oxide nanoparticles (SPIOs); Contrast agents; Cytotoxicity; Magnetic resonance imaging (MRI)

Received July 3, 2012; final acceptance January 28, 2013. Online prepub date: February 5, 2013.
1These authors provided equal contribution to this work.
Address correspondence to Dr. Robin D. Hughes, Institute of Liver Studies, King’s College London School of Medicine, Bessemer Road, London SE5 9PJ, UK. Tel: +44-(0)-20-3299-3137; Fax: +44-(0)-20-3299-3760; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 345-354, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X663604
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Lack of CD47 on Donor Hepatocytes Promotes Innate Immune Cell Activation and Graft Loss: A Potential Barrier to Hepatocyte Xenotransplantation

Nalu Navarro-Alvarez*† and Yong-Guang Yang*†

*Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA
†Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

We have previously shown that interspecies incompatibility of CD47 plays an important role in triggering rejection of xenogeneic hematopoietic cells by macrophages. However, whether CD47 incompatibility also induces rejection of nonhematopoietic cellular xenografts remains unknown. Herein, we have addressed this question in a mouse model of hepatocyte transplantation in which CD47−/− hepatocytes were used to resemble xenografts for CD47 incompatibility. We show that intrasplenic transplantation of CD47−/−, but not wild-type (WT) hepatocytes, into partially hepatectomized syngeneic WT mice resulted in a rapid increase in Mac-1+ cells with an activation phenotype (i.e., Mac-1+CD14+ and Mac-1+CD16/32high), compared to nontransplant controls. In addition, CD47−/− hepatocytes were more severely damaged than WT hepatocytes as indicated by the greater AST and ALT serum levels in these mice. Furthermore, long-term donor hepatocyte survival and liver repopulation were observed in mice receiving WT hepatocytes, whereas CD47−/− hepatocytes were completely rejected within 2 weeks. These results suggest that CD47 on donor hepatocytes prevents recipient myeloid innate immune cell activation, hence aiding in graft survival after hepatocyte transplantation. Thus, CD47 incompatibility is likely to present an additional barrier to hepatocyte xenotransplantation.

Key words: Hepatocyte; Hepatocyte transplantation (HTx); Innate immune cell activation; Graft rejection; Xenotransplantation

Received March 29, 2012; final acceptance January 29, 2013. Online prepub date: February 7, 2013.
Address correspondence to Yong-Guang Yang, M.D., Ph.D., Columbia Center for Translational Immunology, Columbia University, Black Building, 650 W 168th St., New York, NY 10032, USA. Tel: +1-(212)-304-5586; Fax: +1-(646)-426-0036; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 355-363, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368912X661346
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Rapid Dendritic Cell Activation and Resistance to Allotolerance Induction in Anti-CD154-Treated Mice Receiving CD47-Deficient Donor-Specific Transfusion

Yuantao Wang,*1 Hui Wang,†1 Roderick Bronson,‡ Yaowen Fu,* and Yong-Guang Yang*†

*First Hospital of Jilin University, Changchun, China
†Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA
‡Department of Pathology, Harvard Medical School, Boston, MA, USA

CD47–SIRPα signaling plays an important role in regulating macrophage and dendritic cell (DC) activation. Here we investigated the role of CD47 expression on donor cells in tolerance induction by combined treatment with donor-specific transfusion (DST) plus anti-CD154 mAb in a mouse model of fully MHC-mismatched heart allotransplantation. The majority of BALB/c recipient mice that received anti-CD154 and CD47+/+ B6 splenocytes (DST) showed indefinite donor heart survival (median survival time, MST > 150 days). Donor heart survival was improved in anti-CD154-treated BALB/c mice that received CD47+/− (MST = 90 days) or CD47−/− B6 DST (MST = 42 days) when compared to the nontreated (MST = 7 days) and anti-CD154 alone-treated (MST = 15 days) controls, but significantly reduced when compared to mice receiving anti-CD154 plus CD47+/+ B6 DST. Recipient mice treated with anti-CD154 plus CD47−/− or CD47+/− DST also showed significantly increased antidonor, but not anti-third-party, MLR responses compared to those receiving anti-CD154 and CD47+/+ DST. Furthermore, CD47−/− DST induced rapid activation of CD11chiSIRPαhiCD8α− DCs via a mechanism independent of donor alloantigens. These results demonstrated that CD47 expression on donor cells is essential to the success of tolerance induction by combined therapy with DST and CD40/CD154 blockade.

Key words: CD47; Costimulatory blockade; Dendritic cells (DC); Donor-specific transfusion (DST); Signal regulatory protein-α (SIRPα); Transplantation

Received September 30, 2011; final acceptance December 4, 2012. Online prepub date: January 2, 2013.
1These authors provided equal contribution to this work.
Address correspondence to Yong-Guang Yang, M.D., Ph.D., Columbia University College of Physicians and Surgeons, 650 West 168th St., New York, NY 10032, USA. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Yaowen Fu, M.D., Ph.D., First Hospital of Jilin University, 71 Xinmin St., Changchun, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 365-380, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368912X662408
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

An Examination of the Mechanisms by Which Neural Precursors Augment Recovery Following Spinal Cord Injury: A Key Role for Remyelination

Gregory W. J. Hawryluk,*†‡ Stefania Spano,*† Derek Chew,*† Shelly Wang,† Mark Erwin,*‡§ Mahmood Chamankhah,† Nicole Forgione,† and Michael G. Fehlings*†‡¶

*Division of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada
†Institute of Medical Science, University of Toronto, Toronto, ON, Canada
‡Department of Surgery, Division of Neurosurgery, University of Toronto, Toronto, ON, Canada
§Department of Surgery, Division of Orthopedic Surgery, University of Toronto, Toronto, ON, Canada
¶Gerald and Tootsie Halbert Chair, Neural Repair and Regeneration, Toronto Western Hospital, Toronto, ON, Canada

The mechanisms by which neural precursor cells (NPCs) enhance functional recovery from spinal cord injury (SCI) remain unclear. Spinal cord injured rats were transplanted with wild-type mouse NPCs, shiverer NPCs unable to produce myelin, dead NPCs, or media. Most animals also received minocycline, cyclosporine, and perilesional infusion of trophins. Motor function was graded according to the BBB scale. H&E/LFB staining was used to assess gray and white matter, cyst, and lesional tissue. Mature oligodendrocytes and ED1+ inflammatory cells were quantitated. Confocal and electron microscopy were used to assess the relationship between the transplanted cells and axons. Pharmacotherapy and trophin infusion preserved gray matter, white matter, and oligodendrocytes. Trophin infusion also significantly increased cyst and lesional tissue volume as well as inflammatory infiltrate, and functional recovery was reduced. Animals transplanted with wild-type NPCs showed greatest functional recovery; animals transplanted with shiverer NPCs performed the worst. Wild-type NPCs remyelinated host axons. Shiverer NPCs ensheathed axons but did not produce MBP. These results suggest that remyelination by NPCs is an important contribution to functional recovery following SCI. Shiverer NPCs may prevent remyelination by endogenous cells capable of myelin formation. These findings suggest that remyelination is an important therapeutic target following SCI.

Key words: Neural precursor cells (NPCs); Spinal cord injury (SCI); Transplantation; Mechanism; Remyelination

Received August 7, 2011; final acceptance December 15, 2012. Online prepub date: January 28, 2013.
Address correspondence to Michael G. Fehlings, M.D., Ph.D., FRCSC, FACS, Gerald and Tootsie Halbert Chair, Neural Repair and Regeneration, Co-Chairman, Spinal Program, University Health Network, Toronto Western Hospital, McLaughlin Pavilion, 12th Floor Rm. 407, 399 Bathurst St., Toronto, ON, Canada, M5T 2S8. Tel: +1 416 603 5627; Fax: +1 416 603 5298; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23, pp. 381-394, 2014
0963-6897/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X663578
E-ISSN 1555-3892
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Performance and Mechanism of Neuroleukin in the Growth and Survival of Sertoli Cell-Induced Neurons in a Coculture System

Lei Deng,* Bingyang Shi,† Yingping Zhuang,* Ju Chu,* Xiaolin Shi,‡ Siliang Zhang,* and Meijin Guo*

*State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, P.R. China
†School of Chemical Engineering, University of Adelaide, South Australia, Australia
‡Reproductive Medical Center of Capital Medical University, Beijing, P.R. China

Sertoli cells (SCs), which are recognized as the “nurse cells” of the testis due to their important biofunctions, have been used in cotransplantation with neurons in cell therapy. However, it is not clear whether SCs influence neuronal communication and survival. In this study, we showed that approximately 60% of cortical neural stem cells (NSCs) cocultured with SCs differentiated into mature neurons. In addition, the neurite outgrowth and neuronal survival rates were significantly enhanced in the coculture system compared with differentiated neurons induced by a differentiation medium. The neuroleukin (NLK) secretion of SCs was also identified at the RNA and protein level, and the roles of NLK in neuromorphology and physiological regulation were systematically investigated for the first time. These results not only highlight the significance of paracrine regulation of NSCs by SCs but also confirm the role NLK plays in the differentiation and survival of NSCs. Finally, we proposed a possible hypothesis for the mechanism of NLK in the growth and survival of SC-induced neurons based on Western blotting results, which is that NLK secreted by SCs activates the Ras/Raf/MEK/Erk, Jak/Stat, and PI3K/Akt pathways, but not the NF-kB pathway, in neurons resulting in their growth and survival.

Key words: Neuroleukin (NLK); Cortical neural stem cells (NSCs); Sertoli cells (SCs); Coculture; Neuron differentiation; Neurite outgrowth

Received March 15, 2012; final acceptance January 15, 2013. Online prepub date: February 4, 2013.
Address correspondence to Meijin Guo, East China University of Science and Technology, P.O. Box #329, 130 Meilong Road, Shanghai 200237, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Bingyang Shi, School of Chemical Engineering, The University of Adelaide, SA 5005, Australia. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it