Cell Transplantation 20(7) Abstracts

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Cell Transplantation, Vol. 20, pp. 983–1001, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X546599
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Strategies for the Development of Cell Lines for Ex Vivo Gene Therapy in the Central Nervous System

Jana Mejía-Toiber,*1 Claudia G. Castillo,†1 and Magda Giordano*

*Laboratorio de Plasticidad Neuronal, Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México
†Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México

Disorders of the central nervous system (CNS) as a result of trauma or ischemic or neurodegenerative processes still pose a challenge for modern medicine. Due to the complexity of the CNS, and in spite of the advances in the knowledge of its anatomy, pharmacology, and molecular and cellular biology, treatments for these diseases are still limited. The development of cell lines as a source for transplantation into the damaged CNS (cell therapy), and more recently their genetic modification to favor the expression and delivery of molecules with therapeutic potential (ex vivo gene therapy), are some of the techniques used in search of novel restorative strategies. This article reviews the different approaches that have been used and perfected during the last decade to generate cell lines and their use in experimental models of neuronal damage, and evaluates the prospects of applying these methods to treat CNS disorders.

Key words: Central nervous system disorders; Cell lines; Ex vivo gene therapy; Development strategies

1These authors provided equal contribution to this work.
Address correspondence to Magda Giordano, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, P.O. Box 1-1141, Querétaro, Qro., 76230, México. Tel: +52-442-238-1061; Fax: +52-442-238-1046; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1003–1013, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X539128
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Promising Cell-Based Therapy for Bone Regeneration Using Stem Cells From Deciduous Teeth, Dental Pulp, and Bone Marrow

Yoichi Yamada,* Kenji Ito,† Sayaka Nakamura,† Minoru Ueda,† and Tetsuro Nagasaka‡

*Center for Genetic and Regenerative Medicine, Nagoya University School of Medicine, Nagoya, Japan
†Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
‡Laboratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan

We attempted to regenerate bone in a significant osseous defect with various stem cells from deciduous teeth, extracted from puppies, and grafted them into a parent canine mandible as an allograft, parent dental pulp, and bone marrow by tissue engineering and regenerative medicine technology using platelet-rich plasma as an autologous scaffold and signal molecules. Initially, teeth were extracted from a child and parent hybrid canine mandible region and bone marrow (canine mesenchymal stem cells; cMSCs), and parent teeth (canine dental pulp stem cells; cDPSCs), and stem cells were extracted from deciduous teeth (puppy deciduous teeth stem cells; pDTSCs). After 4 weeks, bone defects were prepared on both sides of the mandible with a trephine bar. Graft materials were implanted into these defects: 1) control (defect only), 2) platelet-rich plasma (PRP), 3) cMSCs/PRP, 4) cDPSCs/PRP, and 5) pDTSCs/PRP to investigate the effect of stem cells. The newly formed bones were evaluated by histology and histomorphometric analysis in the defects at 2, 4, and 8 weeks. According to histological observations, the cMSCs/PRP, cDPSCs/PRP, and pDTSCs/PRP groups had well-formed mature bone and neovascularization compared with the control (defect only) and PRP groups at 4 and 8 weeks, respectively, and the mineralized tissues in cMSCs/PRP, cDPSCs/PRP, and pDTSCs/PRP specimens were positive for osteocalcin at 8 weeks. Histometrically, newly formed bone areas were 19.0 ± 2.9% (control), 19.7 ± 6.0% (PRP), 52.8 ± 3.5% (cMSCs/PRP), 61.6 ± 1.3% (cDPSCs/PRP), and 54.7 ± 2.2% (pDTSCs/PRP) at 8 weeks. There were significant differences between cMSCs, cDPSCs, pDTSCs/PRP, and control and PRP groups. These results demonstrate that stem cells from deciduous teeth, dental pulp, and bone marrow with PRP have the ability to form bone, and bone formation with DTSCs might have the potential to generate a graft between a child and parent. This preclinical study could pave the way for stem cell therapy in orthopedics and oral maxillofacial reconstruction for clinical application.

Key words: Tissue engineering and regenerative medicine (TERM); Tissue-engineered bone (TEB); Dental pulp stem cells (DPSCs); Deciduous teeth stem cells (DTSCs); Mesenchymal stem cells (MSCs); Newly formed bone area

Address correspondence to Yoichi Yamada, Center for Genetic and Regenerative Medicine, Nagoya University School of Medicine, 65 Tsurumacho, Showa-ku, Nagoya 466-8550, Japan. Tel: 81-52-744-2348; Fax: 81-52-744-2352; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1015–1031, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X543402
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Autologous Transplantation of Amniotic Fluid-Derived Mesenchymal Stem Cells Into Sheep Fetuses

S. W. Steven Shaw,*†‡ Sveva Bollini,† Khalil Abi Nader,* Annalisa Gastadello,† Vedanta Mehta,* Elisa Filppi,* Mara Cananzi,† H. Bobby Gaspar,§ Waseem Qasim,§ Paolo De Coppi,†1 and Anna L. David*1


*Prenatal Cell and Gene Therapy Group, Institute for Women’s Health, University College London, London, UK
†Surgery Unit, Institute of Child Health, University College London, London, UK
‡Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan
§Department of Paediatric Immunology, Institute of Child Health, University College London, London, UK

Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep (n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3–96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.

Key words: Autologous stem cell transplantation; Amniotic fluid stem cell; Sheep; In utero

1These authors provided equal contribution to this work.
Address correspondence to Anna L. David, M.D., Ph.D., Institute for Women’s Health, University College London, 86-96 Chenies Mews, London, WC1E 6HX, UK. Tel: +44-20 7679-6651; Fax: +44-20 7383-7429; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Paolo de Coppi, M.D., Ph.D., Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK. Tel: +44-20 7905 2641; Fax: +44-20 7404 618; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1033–1047, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X545086
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Protect Against Neuronal Cell Death and Ameliorate Motor Deficits in Niemann Pick Type C1 Mice

Yoojin Seo,*†‡1 Se-Ran Yang,*†‡1 Min Ki Jee,§ Eun Kyung Joo,*†‡ Kyung-Hwan Roh,*†‡ Min-Soo Seo,*†‡ Tae Hee Han,¶ So Yeong Lee,¶ Pan Dong Ryu,¶ Ji-Won Jung,*†‡ Kwang-Won Seo,*†‡ Soo-Kyung Kang,§ and Kyung-Sun Kang*†‡

*Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
†Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
‡Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
§Department of Veterinary Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
¶Department of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea

Niemann Pick disease type C1 (NPC) is an autosomal recessive disease characterized by progressive neurological deterioration leading to premature death. In this study, we hypothesized that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have the multifunctional abilities to ameliorate NPC symptoms in the brain. To test this hypothesis, hUCB-MSCs were transplanted into the hippocampus of NPC mice in the early asymptomatic stage. This transplantation resulted in the recovery of motor function in the Rota Rod test and impaired cholesterol homeostasis leading to increased levels of cholesterol efflux-related genes such as LXRá, ABCA1, and ABCG5 while decreased levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase were observed in NPC mice. In the cerebrum, hUCB-MSCs enhanced neuronal cell survival and proliferation, where they directly differentiated into electrically active MAP2-positive neurons as demonstrated by whole-cell patch clamping. In addition, we observed that hUCB-MSCs reduced Purkinje neuronal loss by suppression of inflammatory and apoptotic signaling in the cerebellum as shown by immunohistochemistry. We further investigated how hUCB-MSCs enhance cellular survival and inhibit apoptosis in NPC mice. Neuronal cell survival was associated with increased PI3K/AKT and JAK2/STAT3 signaling; moreover, hUCB-MSCs modulated the levels of GABA/glutamate transporters such as GAT1, EAAT2, EAAT3, and GAD6 in NPC mice as assessed by Western blot analysis. Taken together, our findings suggest that hUCB-MSCs might play multifunctional roles in neuronal cell survival and ameliorating motor deficits of NPC mice.

Key words: Niemann Pick disease type C1 (NPC); Neurodegeneration; Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs); Neuroprotection

1These authors provided equal contribution to this work.
Address correspondence to Kyung-Sun Kang, D.V.M., Ph.D., Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. Tel: +82-2-880-1246; Fax: +82-2-876-7610; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Soo-Kyung Kang, Ph.D., Department of Veterinary Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1049–1064, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X544915
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Striatal Stimulation Nurtures Endogenous Neurogenesis and Angiogenesis in Chronic-Phase Ischemic Stroke Rats

Takamasa Morimoto,* Takao Yasuhara,* Masahiro Kameda,* Tanefumi Baba,*† Satoshi Kuramoto,* Akihiko Kondo,* Kazuya Takahashi,* Naoki Tajiri,* Feifei Wang,* Jing Meng,* Yuan Wen Ji,* Tomohito Kadota,* Tomoko Maruo,*‡ Kazushi Kinugasa,‡ Yasuyuki Miyoshi,* Tetsuro Shingo,* Cesario V. Borlongan,§ and Isao Date*

*Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
†Department of Neurosurgery, Tokai University, Isehara, Japan
‡National Agency for Automotive Safety & Victims’ Aid Okayama Ryogo Center, Okayama, Japan
§Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, FL, USA

Deep brain stimulation (DBS) is used to treat a variety of neurological disorders including Parkinson’s disease. In this study, we explored the effects of striatal stimulation (SS) in a rat model of chronic-phase ischemic stroke. The stimulation electrode was implanted into the ischemic penumbra at 1 month after middle cerebral artery occlusion (MCAO) and thereafter continuously delivered SS over a period of 1 week. Rats were evaluated behaviorally coupled with neuroradiological assessment of the infarct volumes using magnetic resonance imaging (MRI) at pre- and post-SS. The rats with SS showed significant behavioral recovery in the spontaneous activity and limb placement test compared to those without SS. MRI visualized that SS also significantly reduced the infarct volumes compared to that at pre-SS or without SS. Immunohistochemical analyses revealed a robust neurogenic response in rats that received SS characterized by a stream of proliferating cells from the subventricular zone migrating to and subsequently differentiating into neurons in the ischemic penumbra, which exhibited a significant GDNF upregulation. In tandem with this SS-mediated neurogenesis, enhanced angiogenesis was also recognized as revealed by a significant increase in VEGF levels in the penumbra. These results provide evidence that SS affords neurorestoration at the chronic phase of stroke by stimulating endogenous neurogenesis and angiogenesis.

Key words: Angiogenesis; Chemoattractant; Electrical stimulation; Inflammation; Neural stem/progenitor cells; Neurogenesis

Address correspondence to Takao Yasuhara, M.D., Ph.D., Assistant Professor, Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. Tel: 81-86-235-7336; Fax: 81-86-227-0191; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1065–1086, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X544906
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Schwann Cell Coculture Improves the Therapeutic Effect of Bone Marrow Stromal Cells on Recovery in Spinal Cord-Injured Mice

Xiaoyun Xu,* Nicole Geremia,* Feng Bao,* Anna Pniak,* Melissa Rossoni,* and Arthur Brown*†

*The Spinal Cord Injury Team, BioTherapeutics Research Laboratories and Molecular Brain Research Group, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada
†Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada

Studies of bone marrow stromal cells (MSCs) transplanted into the spinal cord-injured rat give mixed results: some groups report improved locomotor recovery while others only demonstrate improved histological appearance of the lesion. These studies show no clear correlation between neurological improvements and MSC survival. We examined whether MSC survival in the injured spinal cord could be enhanced by closely matching donor and recipient mice for genetic background and marker gene expression and whether exposure of MSCs to a neural environment (Schwann cells) prior to transplantation would improve their survival or therapeutic effects. Mice underwent a clip compression spinal cord injury at the fourth thoracic level and cell transplantation 7 days later. Despite genetic matching of donors and recipients, MSC survival in the injured spinal cord was very poor (~1%). However, we noted improved locomotor recovery accompanied by improved histopathological appearance of the lesion in mice receiving MSC grafts. These mice had more white and gray matter sparing, laminin expression, Schwann cell infiltration, and preservation of neurofilament and 5-HT-positive fibers at and below the lesion. There was also decreased collagen and chondroitin sulphate proteoglycan deposition in the scar and macrophage activation in mice that received the MSC grafts. The Schwann cell cocultured MSCs had greater effects than untreated MSCs on all these indices of recovery. Analyses of chemokine and cytokine expression revealed that MSC/Schwann cell cocultures produced far less MCP-1 and IL-6 than MSCs or Schwann cells cultured alone. Thus, transplanted MSCs may improve recovery in spinal cord-injured mice through immunosuppressive effects that can be enhanced by a Schwann cell coculturing step. These results indicate that the temporary presence of MSCs in the injured cord is sufficient to alter the cascade of pathological events that normally occurs after spinal cord injury, generating a microenvironment that favors improved recovery.

Key words: Bone marrow stromal cells (MSCs); Transplantation; Spinal cord injury; Anti-inflammatory; Stem cells

Address correspondence to Arthur Brown, Spinal Cord Injury Team, Robarts Research Institute, 100 Perth Drive, London, ON N6A 5K8, Canada. Tel: 519-931-5777, ext. 24308; Fax: 519-663-3789; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1087–1097, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X544924
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Presence of Apoptotic Bone Marrow Cells Impairs the Efficacy of Cardiac Cell Therapy

Frederic Mouquet,*† Gilles Lemesle,*† Cedric Delhaye,*† Clement Charbonnel,*† Alexandre Ung,*‡ Delphine Corseaux,*‡ Olivier Fabre,*§ Francis Juthier,*§ Philippe Marchetti,¶ Remi Neviere,*# Eric Van Belle,*† Brigitte Jude,*‡ and Sophie Susen*§

*Université Lille Nord de France, EA 2693, Lille, France
†CHU Lille, Pôle de Cardiologie, Lille, France
‡Pôle d’Hématologie-Transfusion, Lille, France
§Póle de Chirurgie Cardiovasculaire, Lille, France
¶Inserm U8146, Lille, France
#Université Lille Norde de France, EA 44842, Lille, France

Injection of autologous bone marrow cells into infarcted myocardium has been proposed to limit the deterioration of cardiac function following myocardial infarction (MI); unfortunately, the beneficial effects observed have been modest. One of the limiting factors is believed to be poor local survival of the injected cells, but the potential impact of apoptosis among the injected cells has yet to be assessed. Therefore, this study aimed to quantify the apoptosis rate in bone marrow mononuclear cells (BMMCs) prepared for cardiac therapy, and to analyze their effects in vitro on cardiomyoblast apoptosis and in vivo on cardiac function recovery following MI. Using rabbit BMMCs prepared by Ficoll gradient, apoptotic cells were detected via Annexin V (AnV) staining. The effects of depleting the apoptotic cell population by means of AnV magnetic beads was tested in vitro after coculture with cardiomyoblasts (H9c2 cells) and in vivo after cell injection into the infarcted area. Left ventricular ejection fraction and scar extent were assessed by echography and histology 2 months later. After Ficoll gradient isolation, 37.3% (33.4–37.9%) of BMMCs were found to be apoptotic (ApoBase BMMCs). AnV depletion decreased the proportion of apoptotic cells to 20% (17.6–32%) (ApoLow BMMCs). Rabbits treated in vivo with ApoLow BMMCs after MI presented with significantly improved left ventricular ejection fraction [41.4% (41.0–43.6%) vs. 34.6% (34.6–35.9%), p = 0.03), reduced scar extent [20.4% (17.9–24.3%) vs. 25.6% (17.9–27.9%), p = 0.057], and reduced rate of cardiomyocyte apoptosis compared to those treated with ApoBase BMMCs. H9c2 apoptosis was found to be higher after coculture with ApoBase than with ApoLow BMMCs [25.6% (22.6–29.6%) vs. 10.1% (6.6–12.6%), p = 0.03], a result partially reproduced by cocultures with microparticle-rich supernatants from BMMCs. The presence of apoptotic cells among BMMCs impairs the efficacy of cardiac cell therapy after MI, an effect possibly mediated by apoptotic microparticles.

Key words: Cell therapy; Bone marrow; Apoptosis; Myocardial infarction; Annexin V; Cell sorting

Address correspondence to Sophie Susen, M.D., Ph.D., Université Lille Nord de France EA 2693, Hémostase et Pathologie Cardiovasculaire, 1 place de Verdun. 59037 Lille cedex, France. Tel: +33 3.20.44.53.99; Fax: +33 3.20.44.69.89; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1099–1108, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X545068
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

NUP98-HOXA10hd-Expanded Hematopoietic Stem Cells Efficiently Reconstitute Bone Marrow of Mismatched Recipients and Induce Tolerance

Y. Even,* J. L. Bennett,* S. Sekulovic,† L. So,* L. Yi,* K. McNagny,‡ R. K. Humphries,*‡ and F. M. V. Rossi*

*Department of Medicine, The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada
†The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
‡Department of Medical Genetics, The Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada

Gene therapy as well as methods capable of returning cells to a pluripotent state (iPS) have enabled the correction of genetic deficiencies in syngenic adult progenitors, reducing the need for immunosuppression in cell therapy approaches. However, in diseases involving mutations that lead to the complete lack of a protein, such as Duchenne muscular dystrophy, the main immunogens leading to rejection of transplanted cells are the therapeutic proteins themselves. In these cases even iPS cells would not circumvent the need for immunosuppression, and alternative strategies must be developed. One such potential strategy seeks to induce immune tolerance using hematopoietic stem cells originated from the same donor or iPS line from which the therapeutic progenitors are derived. However, donor hematopoietic stem cells (HSCs) are available in limiting numbers and embryonic stem (ES) cell-derived HSCs engraft poorly in adults. While these limitations have been circumvented by ectopic expression of HOXB4, overexpression of this protein is associated with inefficient lymphoid reconstitution. Here we show that adult HSCs expanded with a NUP98-HOXA10hd fusion protein sustain long-term engraftment in immunologically mismatched recipients and generate normal numbers of lymphoid cells. In addition, NUP98-HOXA10hd-expanded cells induce functional immune tolerance to a subsequent transplant of myogenic progenitors immunologically matched with the transplanted HSCs.

Key words: HOXA10; Chimerism; Hematopoietic stem cell (HSC) and myoblast transplantation; Tolerance

Address correspondence to Fabio M. V. Rossi, The Biomedical Research Centre, University of British Columbia, Vancouver, BC, V6T1Z3, Canada, Tel: 604-822-7138; Fax: 604-822-7815; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1109–1115, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X544951E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
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Effect of Splenectomy on Pancytopenia After a Peripheral Blood Stem Cell Transplantation

Jiahua Ding, Wen Bao, Jun Wang, Gang Zhao, Jian Chen, and Huihui Song

Department of Hematology, Zhong Da Hospital, Southeast University, Nanjing, China

To analyze the effect of a splenectomy on pancytopenia after a peripheral blood stem cell transplantation (PBSCT) in chronic myeloid leukemia (CML) patients. Three CML patients diagnosed with splenomegaly in our department from 2002 to 2006 received a splenectomy after PBSCT. Patient 1, a 42-year-old male in chronic phase (CP), received an HLA-identical sibling allo-PBSCT. Patient 2, a 28-year-old female in aggressive phase (AP), received a PBSCT from her twin. Patient 3, a 26-year-old male in chronic phase (CP), received a PBSCT from an unrelated donor. The conditioning regimen included busulfan and cyclophosphamide (BU/CY2). Patients 1, 2, and 3 received splenectomies on days 168, 51, and 114, respectively. Bcrabl transcripts were detected using the polymerase chain reaction (PCR). Chimerism was documented by PCR amplification of a variable number of tandem repeat (VNTR) polymorphrisms. Neither metrisone (2 mg/kg/day for 7 days), mycophenolic acid (MMF) (0.5 g twice daily for 1 month), high-dose γ-globulin (0.4 g/kg/day for 5 days), granulocyte colony-stimulating factor (G-CSF) therapy, nor erythropoietin (EPO) therapy had produced post-PBSCT hematopoiesis recovery. Patients 1 and 2 had 5% Ph-positive chromosomes while patient 3 exhibited graft-versus-host disease (GVHD). After receiving the splenectomy, all three had a rapid hematopoeitic recovery with no evidence of Ph-positive chromosomes, and patients 1 and 3 showed complete donor chimerism (CDC). Patient 1 developed chronic GVHD (cGVHD) on day 210 postsplenectomy that was treated successfully with prednisone. Patient 2 had acute GVHD on day 55 that was treated successfully with dexamethasone (10 mg), administered intravenously once a day for 3 days with good clinical response. To date, patients 1, 2, and 3 have survived postprocedure for 85, 49, and 25 months, respectively. Splenectomy is an effective option for the patients who have pancytopenia after PBSCT and the patients recovered a good graft function after splenectomy without procedure-related complication and with long-time survival. GVHD can develop in both allo-PBSCT and syngeneic PBSCT. A splenectomy after PBSCT may increase the risk of GVHD, enhance the effect of graft versus leukemia (GVL), promote CDC formation.

Key words: Splenectomy; Graft-versus-host disease (GVHD); Allogeneic peripheral blood stem cell transplantation (allo-PBCT)

Address correspondence to Jiahua Ding, Department of Hematology, Zhong Da Hospital, Southeast University, Nanjing, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1117–1126, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X544933
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Bioreactor for the Long-Term Culture of Lung Tissue

Thomas H. Petersen,*† Elizabeth A. Calle,‡ Maegen B. Colehour,‡ and Laura E. Niklason†‡

*Department of Biomedical Engineering, Duke University, Durham, NC, USA
†Department of Anesthesia, Yale University, New Haven, CT, USA
‡Department of Biomedical Engineering, Yale University, New Haven, CT, USA

In this article we describe the design and validation of a bioreactor for the in vitro culture of whole rodent lung tissue. Many current systems only enable large segments of lung tissue to be studied ex vivo for up to a few hours in the laboratory. This limitation restricts the study of pulmonary biology in controlled laboratory settings, and also impacts the ability to reliably culture engineered lung tissues in the laboratory. Therefore, we designed, built, and validated a bioreactor intended to provide sufficient nutrient supply and mechanical stimulation to support cell survival and differentiation in cultured lung tissue. We also studied the effects of perfusion and ventilation on pulmonary cell survival and maintenance of cell differentiation state. The final bioreactor design described herein is capable of supporting the culture of whole native lung tissue for up to 1 week in the laboratory, and offers promise in the study of pulmonary biology and the development of engineered lung tissues in the laboratory.

Key words: Bioreactor; Lung culture; Tissue engineering

Address correspondence to Laura E. Niklason, M.D., Ph.D., Departments of Biomedical Engineering and Anesthesia, Yale University, Room 301D Amistad Building, 10 Amistad Street, New Haven, CT 06520, USA. Tel: 203-737-1422; Fax: 203-737-1484; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1127–1137, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X544942
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
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A Meta-Analysis for Comparison of the Two-Layer and University of Wisconsin Pancreas Preservation Methods in Islet Transplantation

Huanying Qin,* Shinichi Matsumoto,† Goran B. Klintmalm,‡ and Edward B. De Vol*

*Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, TX, USA
†Baylor Institute for Immunology Research, Baylor Health Care System, Dallas, TX, USA
‡Baylor Regional Transplant Institute, Baylor Health Care System, Dallas, TX, USA

Conflicting results have been reported on the effectiveness of the two-layer method (TLM) compared with the University of Wisconsin (UW) method for preserving pancreata. The objective of this study was to compile the evidence for or against any difference in human islet yield and viability between these two. PubMed (January 2000 to May 2008) and Cochran Library searches were performed and 17 studies were included for the meta-analysis. Data on donor characteristics, preservation time, and outcomes were abstracted. Studies were subgrouped based on how TLM was used (UW + TLM or TLM alone), on mean cold ischemic time (CIT) (>20 h or <20 h), and on whether special chemical was used (yes or no). Meta-analysis of all studies and subgroups was performed and the pooled standardized mean differences (SMD) with 95% confidence intervals (CI) were reported. Overall, the use of TLM significantly increased islet yield [SMD, 0.74 (0.44–1.04)] and viability [SMD, 0.63 (0.14–1.12)]. The beneficial effects of TLM on islet yield were more evident when TLM was used following UW storage or when prolonged CIT was used. TLM used alone, shorter CIT, and no chemical use all resulted in similar islet viability between TLM and UW groups. Beneficial effects of TLM on islet viability were demonstrated only when TLM was used following UW storage, or with prolonged CIT, or with chemical use. In conclusion, the TLM was beneficial for prolonged pancreas preservation before human islet isolation; however, benefit of the TLM for short-term preservation was not clear.

Key words: Meta-analysis; Pancreas preservation; University of Wisconsin solution; Two-layer method

Address correspondence to Huanying Qin, M.S., Baylor Health Care System, 8080 North Central Expressway, Suite 500, Dallas, TX 75206, USA. Tel: (214) 820-9064; Fax: (214) 265-3628; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 20, pp. 1139–1151, 2011
0963-6897/11 $90.00 + .00
DOI: 10.3727/096368910X550170
E-ISSN 1555-3892
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Sequential Combination of a JNK Inhibitor and Simvastatin Protects Porcine Islets From Peritransplant Apoptosis and Inflammation

Sang-Man Jin,*†‡ Kang Seok Kim,*†‡ Song-Yi Lee,*†‡ Chang-Hoon Gong,*†‡ Su Kyoung Park,*†‡ Jun Seop Shin,*†‡ Chung-Gyu Park,*†‡§¶ and Sang-Joon Kim*¶#

*Xenotransplantation Research Center, Seoul National University Hospital, Seoul, Republic of Korea
†Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
‡Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
§Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
¶Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
#Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea

Intraductal administration of a c-Jun NH2-terminal kinase (JNK) inhibitor enhances islet viability. However, its role in reducing the inflammatory response in islets is unknown. It is also unknown whether a JNK inhibitor could act in synergy with statins. We examined if the sequential combination of a JNK inhibitor and simvastatin would reduce islet inflammation and improve islet viability. We performed porcine islet isolation with or without intraductal administration of SP600125, a JNK inhibitor. This was followed by culture medium supplementation with either nicotinamide alone or nicotinamide plus simvastatin. We assessed the viability of islets by flow cytometry, islet loss during overnight culture, graft function in NOD/SCID mice, and expression of inflammation-related genes in islets. The sequential combination of a JNK inhibitor and simvastatin increased the β-cell viability index of porcine islets cultured overnight (p = 0.015) as well as islet viability as assessed by a DNA binding dye staining (p = 0.011). The combination of a JNK inhibitor and simvastatin significantly increased the islet survival rate (p = 0.027) when the histomorphometry of donor pancreas indicated a large islet proportion of greater than 50.55%. When we transplanted the same islet mass per recipient for each group, there was no difference in overall islet graft function. Intraductal administration of JNK inhibitor significantly suppressed mRNA expression levels of interleukin-1β (IL-1β), interferon-γ, tumor necrosis factor-α, IL-6, IL-8, and macrophage chemoattractant protein-1. It also decreased the concentration of IL-1β (p = 0.040) and IL-8 (p = 0.023) in the culture supernatant. In conclusion, the sequential combination of a JNK inhibitor and simvastatin protected porcine islets from peritransplant apoptosis. Inhibition of JNK reduced the inflammatory response and could be considered an alternative target for suppression of porcine islet inflammation.

Key words: Porcine; Islet; Inflammation; Apoptosis

Address correspondence to Chung-Gyu Park, M.D., Ph.D., Department of Microbiology and Immunology, Xenotransplantation Research Center, Seoul National University College of Medicine, 103 Daehak-ro Jongno-gu, Seoul 110-799, Republic of Korea. Tel: +82-2-740-8308; Fax: +82-2-743-0881; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it