Cell Transplantation 22(S1) Abstracts

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Cell Transplantation, Vol. 22, Supplement 1, pp. S5-S10, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672082
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Review

Standard Recommendations for the Application of Chinese Clinical Cell Therapy for Neurorestoration (2012)

Chinese Branch of the International Association of Neurorestoratology (IANR) and the Preparatory Committee of Chinese Association of Neurorestoratology

Cell therapy has been shown to be a promising alternative therapy for neurorestoration, and more than 30 different types of cells have been shown to possess some capability to restore lost or damaged neurological functions. Chinese physicians have successfully applied cell therapy to many neurological diseases and damages in the clinic and contributed to establish a discipline of neurorestoratology. To standardize the clinical procedures of cell therapy as one of the strategies for treating neurological disorders, the Chinese Branch of the International Association of Neurorestoratology (IANR) and the Preparatory Committee of Chinese Association of Neurorestoratology recently completed the Standard Recommendations (2012) for the Application of Chinese Clinical Cell Therapy for Neurorestoration. We hope these recommendations will guide clinical practice in applying cell therapy for neurorestoration, which will therein offer a reference for both Chinese and other countries’ governments to make relevant official regulations. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Standard; Clinical application; Cell therapy; Neurorestoration; China

Received December 26, 2012; final acceptance August 13, 2013. Online prepub date: August 29, 2013.
Address correspondence to Hongyun Huang, Center of Neurorestoratology, Beijing Rehabilitation Hospital Affiliated Capital Medical University, Beijing 100144, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S11-S19, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672091
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Review

Cell Transplantation as a Pain Therapy Targets Both Analgesia and Neural Repair

Lin Chen,*†‡ Hongyun Huang,*‡ Hari Shanker Sharma,§ Huancong Zuo,† and Paul Sanberg¶

*Beijing Hongtianji Neuroscience Academy, Beijing, China
†Medical Center, Tsinghua University, Beijing, China
‡Department of Neurosurgery, Beijing Rehabilitation Hospital Affiliated Capital Medical University, Beijing, China
§Laboratory of Cerebrovascular Research, Department of Surgical Sciences Anaesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, Sweden
¶Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA

Cell transplantation is a potentially powerful approach for the alleviation of chronic pain. The strategy of cell transplantation for the treatment of pain is focused on cell-based analgesia and neural repair. (1) Adrenal medullary chromaffin cells and the PC12 cell line have been used to treat cancer pain and neuropathic pain in both animal models and human cases. As biological or living minipumps, these cells produce and secrete painreducing neuroactive substances if administered directly into the spinal subarachnoid space. (2) Cell implantation for pain neurorestorative therapy is a new concept and an emerging research field for pain control along with neural repair. Possible neurorestorative mechanisms include neuroprotective, neurotrophic, neuroreparative, neuroregenerative, neuromodulation, or neuroconstructive interventions, as well as immunomodulation and enhancing the microcirculation. These factors may ultimately restore the damaged or irritated condition of the lesioned nerves. The growing preclinical and clinical data show that neural stem/progenitor cells, olfactory ensheathing cells, mesenchymal stromal cells, and CD34+ cells have the capacity to manage intractable pain and improve neurological functions. Cell delivery routes include local, intrathecal, or intravascular implants. Although these strategies are still in their infancy phase for pain neurorestoratology, cell-based therapies could open up new avenues for the relief of pain. In this review, these aspects are critically analyzed based on our own investigations. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Cell transplantation; Pain; Analgesia; Neural repair; Neurorestorative therapy; Pain neurorestoratology

Received December 26, 2012; final acceptance August 13, 2013. Online prepub date: August 29, 2013.
Address correspondence to Hongyun Huang, Beijing Hongtianji Neuroscience Academy, Lingxiu Building, Shijingshan District, Beijing 100143, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Huancong Zuo, Medical Center, Tsinghua University, Beijing, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S21-S25, 2013
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DOI: http://dx.doi.org/10.3727/096368913X672127
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Long-Term Outcome of Olfactory Ensheathing Cell Transplantation in Six Patients With Chronic Complete Spinal Cord Injury

Yaojian Rao,*1 Wenxiao Zhu,*1 Yanxing Guo,* Chunxia Jia,* Ran Qi,* Ruofei Qiao,* Danna Cao,* Hongxing Zhang,* Zesheng Cui,* Lei Yang,* and Yongjun Wang†

*Department of Spine Surgery, Luoyang Orthopedic Hospital of Henan Province, Luoyang, P.R. China
†Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China

The aim of the study was to analyze the clinical efficacy and safety of olfactory ensheathing cell (OEC) transplantation for treating patients with chronic, complete spinal cord injury (SCI). Six patients with six chronic complete spinal cord injuries were recruited and treated with autologous OEC transplantation and followed for 24 months. The scores from before and after transplantation were analyzed. This was a self-control experiment. There was significant amelioration in the scores of the standard neurological classification of spinal cord injury made by the America Spinal Cord Injury Association (ASIA) and the International Association of Neurorestoratology–Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) following OEC transplantation with 24 months of follow-up. No clinical complications were observed. OEC transplantation would appear to be clinically safe and may promote the neurofunctional recovery of SCI based on data from six patients. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Olfactory ensheathing cells (OECs); Cell transplantation; Spinal cord injuries; Clinical effect; Safety

Received December 26, 2012; final acceptance August 20, 2013. Online prepub date: August 29, 2013.
1These authors provided equal contribution to this work.
Address correspondence to Yaojian Rao, Department of Spine Surgery, Luoyang Orthopedic Hospital of Henan Province, Luoyang, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S27-S38, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672118
E-ISSN 1555-3892
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Cotransplantation of Olfactory Ensheathing Cells and Schwann Cells Combined With Treadmill Training Promotes Functional Recovery in Rats With Contused Spinal Cords

Tiansheng Sun,* Chaoqun Ye,* Zhicheng Zhang,* Jun Wu,* and Hongyun Huang†

*Orthopaedic Department, The Beijing Army General Hospital, Beijing, China
†Beijing Hongtianji Neuroscience Academy, Beijing, China

The present study investigated the ability of cotransplantation of Schwann cells (SCs) and olfactory ensheathing cells (OECs) combined with treadmill training in facilitating neuronal plasticity and promoting hindlimb function recovery of subacute moderate thoracic (T10) spinal cord contusion in rats. Two weeks postinjury, SCs were injected directly into the lesion, while OECs were injected into the adjacent tissues. The treadmill training with the rats began postinjury on day 7, with each session lasting 20 ± 10 min per day, 5 days per week, for 10 weeks. At the 11th week postinjury, OECs were found migrating longitudinally and laterally from the injection site to the injury site through the gray and white matter, while some traveled along the central canal or pia. The SCs remained densely packed and concentrated at the transplant site. The transplanted SCs supported ingrowth of numerous, densely populated neurofilament-positive (NF+), MBP+ axons. The OECs promoted elongation of moderate NF+, GAP-43+ axons and a few MBP+ axons in parallel with OEC processes. The GFAP immunoreactivity in the spared tissue surrounding the graft of SCs and OECs at the lesion site was less intense than that in the DMEM group. Treadmill training had no effect on GFAP immunoreactivity. Treadmill training increased the number of TH-immunoreactive neurons in the gray matter of L2 spinal cord. Moreover, cotransplantation of OECs and SCs significantly increased the BBB score during 5–8 weeks postinjury alongside treadmill training between 5 and 11 weeks. Cotransplantation of OECs and SCs combined with treadmill training resulted in the highest BBB score at 4 and 11 weeks. The study details the differential mechanisms of neuronal plasticity: (1) axon growth and remyelination induced by cotransplantation of OECs and SCs and (2) neuron plasticity below the lesion enhanced by treadmill training. The synergistic effects of the combined strategy enhance functional recovery. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Olfactory ensheathing cell and Schwann cell cotransplantation; Treadmill training; Spinal cord contusion; Neuronal plasticity; Functional recovery

Received December 26, 2012; final acceptance August 13, 2013. Online prepub date: August 29, 2013.
Address correspondence to Professor Tiansheng Sun, Orthopaedic Department, The Beijing Army General Hospital, Beijing 100700, China. Tel: +86 10 66721207; Fax: +86 10 84042490; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S39-S50, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672190
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Control of Olfactory Ensheathing Cell Behaviors by Electrospun Silk Fibroin Fibers

Zhihai Fan,*1 Yixin Shen,*1 Feng Zhang,†1 Baoqi Zuo,‡ Qiang Lu,‡ Peng Wu,* Zonggang Xie,* Qirong Dong,* and Huanxiang Zhang†

*Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou Jiangsu, People’s Republic of China
†Department of Cell Biology, Medical College of Soochow University, Jiangsu Province Key Laboratory of Stem Cell Research, Suzhou, People’s Republic of China
‡College of Textile and Clothing Engineering, National Engineering Laboratory for Modern Silk, Soochow University, Suzhou, People’s Republic of China

Olfactory ensheathing cells (OECs), the only glial cell type that normally penetrates the transition zone between the peripheral and central nervous systems, are one of the most promising candidates for cell transplantation in repairing spinal cord injury (SCI). However, we must manipulate and regulate OECs’ behavior to make these cells effective in cell transplantation. In the present study, we assessed the response of rat OECs to different variants of nanofibrous silk fibroin mats with regard to cell morphology, adhesion, proliferation, and migration and the related gene and protein expression. Results showed that OECs adhere and spread more easily on Tussah silk fibroin (TSF) fibers than Bombyx mori silk fibroin fibers, resulting in a higher rate of cell proliferation and gene and protein expression, examined by RT-PCR and ELISA. In addition, the morphology of OECs on microfibers is mainly polygonal with short protrusions, whereas the OECs on nanofibers exhibit a bipolar shape with long protrusions that align along the fibers, especially when aligned fibers are employed. Moreover, OECs on silk fibroin nanofibers migrate more efficiently than those on poly-l-lysine (PLL). Based on the experimental results, the morphology, adhesion, spread, gene and protein expression, and migration of OECs could be modulated and regulated by adjusting the contents and structure of silk fibroin nanofibers, shedding light on the control of OECs’ behavior in nerve tissue engineering and thus the future therapeutic intervention for nerve repair after injury. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Olfactory ensheathing cells (OECs); Electrospun fibers; Tussah silk fibroin (TSF); Bombyx mori silk fibroin (BSF); Fiber diameter; Alignment

Received December 26, 2012; final acceptance September 24, 2013. Online prepub date: October 22, 2013.
1These authors provided equal contribution to this work.
Address correspondence to Qirong Dong, Department of Orthopedics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou Jiangsu 215006, People’s Republic of China. Tel: +86-512-67784115; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Huanxiang Zhang, Department of Cell Biology, Medical College of Soochow University, Jiangsu Province Key Laboratory of Stem Cell Research, Suzhou 215123, People’s Republic of China. Tel: +86 512-65880277; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S51-S65, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672208
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Intracranial Transplant of Olfactory Ensheathing Cells Can Protect Both Upper and Lower Motor Neurons in Amyotrophic Lateral Sclerosis

Ying Li,*† Lin Chen,*‡ Yanxiu Zhao,*§ Jianling Bao,* Juan Xiao,* Jingyuan Liu,* Xiaorong Jiang,* Changman Zhou,*¶ Hongmei Wang,* and Hongyun Huang*‡

*Beijing Hongtianji Neuroscience Academy, Lingxiu Building, Shijingshan District, Beijing, China
†Reproductive and Genetic Center of National Research Institute for Family Planning, Peking Union Medical College, Beijing, China
‡Division of Neurorestoratology, Yuquan Hospital, Tsinghua University, Beijing, China
§Department of Neurobiology, Taishan University, Taishan, Shandong, China
¶Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China

Amyotrophic lateral sclerosis (ALS) is a fatal disease that involves the degeneration of cortical and spinal motor neurons. Mutant SOD1G93A rats constitute a good animal model for this pathological condition. We have previously demonstrated that transplantation of neonatal olfactory ensheathing cells (OECs) into the dorsal funiculus of the spinal cord of mutant SOD1G93A transgenic rats increases the survival of spinal motor neurons and remyelinates the impaired axons through the pyramidal tract. In the present study, we examine whether intracranial cell implantation could also exert a similar effect on cortical motor neurons and on the lower motor neurons in the spinal cord. We injected OECs from the bulb of 7-day-old GFP green rats into the corona radiate of adult SOD1 mutant rats stereotaxically to observe any changes of the upper motor neurons as well as the lower motor neurons. We found that more motor neurons at both the motor cortices and ventral horns of the spinal cord survived in grafted ALS rats than in control rats. Prolonged survival and behavioral tests including a screen test, hind limb extension, rotarod, and gait control showed that the treated animals were better than the control group. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Olfactory ensheathing cells (OECs); Amyotrophic lateral sclerosis (ALS); Cu/Zn superoxide dismutase 1 mutant (SOD1G93A); Behavior; Motor neurons

Received December 26, 2012; final acceptance August 15, 2013. Online prepub date: August 29, 2013.
Address correspondence to Hongyun Huang, Beijing Hongtianji Neuroscience Academy, Lingxiu Building, Shijingshan District, Beijing 100143, China. Tel: +86-13910116608; Fax: +86-10-58411195; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S67-S82, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672172
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Encapsulation of Mesenchymal Stem Cells by Bioscaffolds Protects Cell Survival and Attenuates Neuroinflammatory Reaction in Injured Brain Tissue After Transplantation

Anna Sarnowska,* Anna Jablonska,* Marcin Jurga,† Maria Dainiak,‡ Lukasz Strojek,* Katarzyna Drela,* Kathleen Wright,† Anuj Tripathi,§ Ashok Kumar,§ Hans Jungvid,‡ Barbara Lukomska,* Nico Forraz,† Colin McGuckin,† and Krystyna Domanska-Janik*

*NeuroRepair Department, Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
†Cell Therapy Research Institute, Meyzieu-Lyon, France
‡Protista Biotechnology AB, IDEON, Lund, Sweden
§Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, India

Since the brain is naturally inefficient in regenerating functional tissue after injury or disease, novel restorative strategies including stem cell transplantation and tissue engineering have to be considered. We have investigated the use of such strategies in order to achieve better functional repair outcomes. One of the fundamental challenges of successful transplantation is the delivery of cells to the injured site while maintaining cell viability. Classical cell delivery methods of intravenous or intraparenchymal injections are plagued by low engraftment and poor survival of transplanted stem cells. Novel implantable devices such as 3D bioactive scaffolds can provide the physical and metabolic support required for successful progenitor cell engraftment, proliferation, and maturation. In this study, we performed in situ analysis of laminin-linked dextran and gelatin macroporous scaffolds. We revealed the protective action of gelatin–laminin (GL) scaffolds seeded with mesenchymal stem cells derived from donated human Wharton’s jelly (hUCMSCs) against neuroinflammatory reactions of injured mammalian brain tissue. These bioscaffolds have been implanted into (i) intact and (ii) ischemic rat hippocampal organotypic slices and into the striatum of (iii) normal and (iv) focally injured brains of adult Wistar rats. We found that transplantation of hUCMSCs encapsulated in GL scaffolds had a significant impact on the prevention of glial scar formation (low glial acidic fibrillary protein) and in the reduction of neuroinflammation (low interleukin-6 and the microglial markers ED1 and Iba1) in the recipient tissue. Moreover, implantation of hUCMSCs encapsulated within GL scaffolds induced matrix metalloproteinase-2 and -9 proteolytic activities in the surrounding brain tissue. This facilitated scaffold biodegradation while leaving the remaining grafted hUCMSCs untouched. In conclusion, transplanting GL scaffolds preseeded with hUCMSCs into mammalian brain tissue escaped the host’s immune system and protected neural tissue from neuroinflammatory injury. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Human mesenchymal stem cells (hMSCs); Bioactive scaffolds; Tissue engineering; Brain injury; Stem cell niche

Received December 26, 2012; final acceptance August 23, 2013. Online prepub date: September 10, 2013. Address correspondence to Anna Sarnowska, NeuroRepair Department, Medical Research Institute, Po


Cell Transplantation, Vol. 22, Supplement 1, pp. S83-S91, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672154
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Multiple Cell Transplantation Based on an Intraparenchymal Approach for Patients With Chronic Phase Stroke

Lin Chen,*†‡1 Haitao Xi,†§1 Hongyun Huang,*†§ Feng Zhang,†§ Yancheng Liu,*† Di Chen,† and Juan Xiao†

*Center of Neurorestoratology, Beijing Rehabilitation Hospital Affiliated Capital Medical University, Beijing, China
†Beijing Hongtianji Neuroscience Academy, Lingxiu Building, Beijing, China
‡Medical Center, Tsinghua University, Beijing, China
§Department of Neurorestoratology, Jingdong Zhongmei Hospital, Hebei, China

Stroke is the third leading cause of death worldwide and a huge perpetrator in adult disability. This pilot clinical study investigates the possible benefits of transplanting multiple cells in chronic stroke. A total of 10 consecutive stroke patients were treated by combination cell transplantation on the basis of an intraparenchymal approach from November 2003 to April 2011. There were six males and four females. Their age ranged from 42 to 87 years, and the course of disease varied from 6 months to 20 years. Six patients suffered cerebral infarction, and four patients suffered a brain hemorrhage. The olfactory ensheathing cells, neural progenitor cells, umbilical cord mesenchymal cells, and Schwann cells were injected through selected routes including intracranial parenchymal implantation, intrathecal implantation, and intravenous administration, respectively. The clinical neurological function was assessed carefully and independently before treatment and during a long-term follow-up using the Clinic Neurologic Impairment Scale and the Barthel index. All patients were followed up successfully from 6 months to 2 years after cell transplantation. Every subject achieved neurological function amelioration including improved speech, muscle strength, muscular tension, balance, pain, and breathing; most patients had an increased Barthel index score and Clinic Neurologic Impairment Scale score. These preliminary results demonstrate the novel strategy of combined multiple cell therapy based on intraparenchymal delivery: it appears to be relatively clinically safe and at least initially beneficial for chronic stroke patients. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Chronic stroke; Multiple cells; Transplantation; Intraparenchymal approach; Human; Clinical study

Received December 26, 2012; final acceptance August 20, 2013. Online prepub date: August 29, 2013.
1These authors are coauthors.
Address correspondence to Hongyun Huang, Center of Neurorestoratology, Beijing Rehabilitation Hospital Affiliated Capital Medical University, Beijing 100144, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S93-S99, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672145
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Preliminary Report of Multiple Cell Therapy for Patients With Multiple System Atrophy

Haitao Xi,*† Lin Chen,*‡§ Hongyun Huang,*‡ Feng Zhang,*† Yancheng Liu,*‡ Di Chen,* and Juan Xiao*

*Beijing Hongtianji Neuroscience Academy, Beijing, China
†Department of Neurorestoratology, Jingdong Zhongmei Hospital, Hebei Province, China
‡Center of Neurorestoratology, Beijing Rehabilitation Hospital Affiliated Capital Medical University, Beijing, China
§Medical Center, Tsinghua University, Beijing, China

The aim of this study is to explore the safety and therapeutic effect of multiple cell transplantations on patients with multiple system atrophy. Ten patients suffering from multiple system atrophy were treated by multiple cell transplantations from August 2005 to March 2011. They were six males and four females, with an average age of 51.90 ± 12.92 years (23–66 years). Multiple cell types were transplanted by intravenous, intrathecal, and intracranial routes; for example, 0.4–0.5 × 106/kg umbilical cord mesenchymal cells by intravenous drip, intrathecal implantation of 2.0 × 106 Schwann cells and 2.0–5.0 × 106 neural progenitor cells through cerebellar cistern puncture, or 2 × 106 olfactory ensheathing cells and 4 × 106 neural progenitor cells injected into key points for neural network restoration (KPNNR). The neurological function was assessed before and after treatment with the International Cooperative Ataxia Rating Scale (ICARS) by the World Federation of Neurology and the Unified Multiple System Atrophy Rating Scale (UMSARS). The patients achieved neurological function amelioration after treatment, which included improvements in walking ability, gaits, standing, speech, and muscular tension; the ICARS score decreased from a preoperative 46.30 ± 14.50 points to postoperative 41.90 ± 18.40 points (p = 0.049). The UMSARS score decreased from preoperative 50.00 ± 20.65 points to postoperative 46.56 ± 23.05 points (p = 0.037). Among them, two patients remained stable and underwent a second treatment 0.5–1 year after the first therapy. After treatment, five patients were followed up for more than 6 months. Balance and walking ability improved further in four patients, while one patient remained stable for over 6 months. In conclusion, a strategy of comprehensive cell-based neurorestorative therapy for patients with multiple system atrophy is safe and appears to be beneficial. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Multiple system atrophy; Multiple cells; Comprehensive neurorestoration; Transplantation

Received December 26, 2012; final acceptance August 20, 2013. Online prepub date: August 29, 2013.
Address correspondence to Hongyun Huang, Center of Neurorestoratology, Beijing Rehabilitation Hospital Affiliated Capital Medical University, Beijing 100144, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S101-S112, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672163
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Neural Stem/Progenitor Cell Transplantation for Cortical Visual Impairment in Neonatal Brain Injured Patients

Zuo Luan,1 Suqing Qu,1 Kan Du, Weipeng Liu, Yinxiang Yang, Zhaoyan Wang, Ying Cui, and Qingan Du

Department of Pediatrics, Navy General Hospital, Beijing, China

The purpose of this study was to investigate the clinical efficacy of neural stem/progenitor cell (NS/PC) transplantation to treat severe cortical visual impairment (CVI), a sequela of neonatal brain injury. Fifty-two patients with cerebral injury and CVI were randomly divided into two groups: the treatment group (n = 25, with the median age of 18 months) and the control group (n = 27, with the median age of 19.5 months). The treatment group received intracerebroventricular transplantation of human NS/PCs and rehabilitation training. The control group received rehabilitation only. The visual function was assessed by Holt’s method at various time points after transplantation. One in five patients with fundus abnormalities accompanied by blindness regained light perception. The visual functions of 75% of the patients with normal fundus were improved by one level or more in a 2-year follow-up. The median efficacy appeared 60 days posttransplantation. The total effective rate of cell transplantation on visual improvement was 64% (16 patients of 25), among which one blind patient regained light perception, five (31.2%) CVI patients improved by one level, and 10 (62.5%) improved by more than one level. Functional magnetic resonance imaging (fMRI) in a subpopulation of patients showed enhanced signals in the occipital lobe, visual pathway, and apical lobe after transplantation. In the control group, four patients with fundus abnormalities showed no improvement. Nine of 23 CVI patients with normal fundus improved visual function by more than one level. At the 2-year follow-up, no blind patients showed visual improvement. The total effective rate was 33.33% (9 of 27 patients). Among those showing visual improvement in the control group, six patients (66.67%) improved by one level, and three (33.33%) by more than one level. The median efficacy occurred in 365 days. Human NS/PC transplantation is effective to treat patients with severe CVI after neonatal brain injury. Compared with the traditional rehabilitation training, cell transplantation showed not only earlier visual improvement but also higher improvement rates and degrees. This article is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Brain injury; Visual impairment; Neural stem/progenitor cells; Transplantation; Children

Received December 26, 2012; final acceptance August 29, 2013. Online prepub date: September 10, 2013.
1These authors provided equal contribution to this work.
Address correspondence to Zuo Luan, Department of Pediatrics, Navy General Hospital, No. 6, Fucheng Road, 100048, Beijing, China. Tel: +86 10 66958303; Fax: +86 10 66958303; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S113-S126, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672181
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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Intracerebral Transplantation of Adipose-Derived Mesenchymal Stem Cells Alternatively Activates Microglia and Ameliorates Neuropathological Deficits in Alzheimer’s Disease Mice

Tuo Ma,*1 Kai Gong,*1 Qiang Ao,†1 Yufang Yan,* Bo Song,* Hongyun Huang,† Xiufang Zhang,* and Yandao Gong*

*State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing, China
†Institute of Neurological Disorders, Yuquan Hospital, Tsinghua University, Beijing, China

Recent studies suggest that transplantation of mesenchymal stem cells might have therapeutic effects in preventing pathogenesis of several neurodegenerative disorders. Adipose-derived mesenchymal stem cells (ADSCs) are a promising new cell source for regenerative therapy. However, whether transplantation of ADSCs could actually ameliorate the neuropathological deficits in Alzheimer’s disease (AD) and the mechanisms involved has not yet been established. Here, we evaluated the therapeutic effects of intracerebral ADSC transplantation on AD pathology and spatial learning/memory of APP/PS1 double transgenic AD model mice. Results showed that ADSC transplantation dramatically reduced β-amyloid (Aβ) peptide deposition and significantly restored the learning/memory function in APP/PS1 transgenic mice. It was observed that in both regions of the hippocampus and the cortex there were more activated microglia, which preferentially surrounded and infiltrated into plaques after ADSC transplantation. The activated microglia exhibited an alternatively activated phenotype, as indicated by their decreased expression levels of proinflammatory factors and elevated expression levels of alternative activation markers, as well as Aβ-degrading enzymes. In conclusion, ADSC transplantation could modulate microglial activation in AD mice, mitigate AD symptoms, and alleviate cognitive decline, all of which suggest ADSC transplantation as a promising choice for AD therapy. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Alzheimer’s disease (AD); Adipose-derived mesenchymal stem cells (ADSCs); Transplantation; Microglia

Received December 26, 2012; final acceptance August 26, 2013. Online prepub date: September 18, 2013.
1These authors provided equal contribution to this work.
Address correspondence to Yandao Gong, School of Life Sciences, Tsinghua University, Beijing 100084, China. Tel: +86-10-62785049; Fax: +86-10-62794214; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S127-S138, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672136
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
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A Clinical Study Shows Safety and Efficacy of Autologous Bone Marrow Mononuclear Cell Therapy to Improve Quality of Life in
Muscular Dystrophy Patients

Alok Sharma,* Hemangi Sane,† Prerna Badhe,* Nandini Gokulchandran,* Pooja Kulkarni,† Mamta Lohiya,‡ Hema Biju,‡ and V. C. Jacob‡

*Department of Medical Services and Clinical Research, NeuroGen Brain and Spine Institute, Surana Sethia Hospital and Research Centre, Suman Nagar, Sion-Trombay Road, Chembur, Mumbai, India
†Department of Research & Development, NeuroGen Brain and Spine Institute, Surana Sethia Hospital and Research Centre, Suman Nagar, Sion-Trombay Road, Chembur, Mumbai, India
‡Department of NeuroRehabilitation, NeuroGen Brain and Spine Institute, Surana Sethia Hospital and Research Centre, Suman Nagar, Sion-Trombay Road, Chembur, Mumbai, India

Muscular dystrophy is a genetic disorder with no definite cure. A study was carried out on 150 patients diagnosed with muscular dystrophy. These included Duchenne muscular dystrophy, limb-girdle muscular dystrophy, and Becker muscular dystrophy variants. They were administered autologous bone marrow-derived mononuclear cells intrathecally and intramuscularly at the motor points of the antigravity weak muscles followed by vigorous rehabilitation therapy. No significant adverse events were noted. Assessment after transplantation showed neurological improvements in trunk muscle strength, limb strength on manual muscle testing, gait improvements, and a favorable shift on assessment scales such as the Functional Independence Measure and the Brooke and Vignos Scales. Furthermore, imaging and electrophysiological studies also showed significant changes in selective cases. On a mean follow-up of 12 ± 1 months, overall 86.67% cases showed symptomatic and functional improvements, with six patients showing changes with respect to muscle regeneration and a decrease in fatty infiltration on musculoskeletal magnetic resonance imaging and nine showing improved muscle electrical activity on electromyography. Fifty-three percent of the cases showed an increase in trunk muscle strength, 48% showed an increase in upper limb strength, 59% showed an increase in lower limb strength, and approximately 10% showed improved gait. These data were statistically analyzed using Student’s paired t test and found to be significant. The results show that this treatment is safe and efficacious and also improves the quality of life of patients having muscular dystrophy. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Muscular dystrophy; Autologous; Bone marrow; Mononuclear cells; Quality of life

Received December 26, 2012; final acceptance September 4, 2013. Online prepub date: September 10, 2013.
Address correspondence to Alok Sharma, M.S., M.Ch., Consultant Neurosurgeon, NeuroGen Brain and Spine Institute, Surana Sethia Hospital and Research Centre, Suman Nagar, Sion-Trombay Road, Chembur, Mumbai 400071, India. Tel: +91-022-25283706/+91-022-25281610; Fax: +91-022-25292250; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 22, Supplement 1, pp. S139-S146, 2013
0963-6897/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368913X672109
E-ISSN 1555-3892
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Safety of Granulocyte Colony-Stimulating Factor (G-CSF) Administration for Postrehabilitated Motor Complete Spinal Cord Injury Patients: An Open-Label, Phase I Study

Nazi Derakhshanrad,* Hooshang Saberi,*† Mir Saeed Yekaninejad,*‡ Ghazale Eskandari,* Azam Mardani,* Fereshte Rahdari,* and Keyvan Tayebi Meybodi†

*Brain and Spinal Injuries Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
†Department of Neurosurgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
‡Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Granulocyte colony-stimulating factor (G-CSF) is a major growth factor in the activation and differentiation of granulocytes. This cytokine has been widely and safely employed in different conditions over many years. In this translational study, G-CSF is administered to 19 patients with chronic motor complete spinal cord injury, and outcomes are reported. All 19 patients received subcutaneous G-CSF (5 μg/kg per day) for 5 days and were followed for at least 6 months. The American Spinal Injury Association (ASIA) scale was used for motor and sensory assessment, and the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) and the Spinal Cord Independence Measure (SCIM) III were used to assess improvements in the ability to perform basic daily tasks. At the 6-month follow-up, upper extremity motor scores improved by 10, which was statistically significant (p = 0.007), whereas there were no significant changes in lower extremity motor scores. Also, the median of light touch sensory scores improved by 5 (p = 0.001). Pinprick sensory scores significantly improved (p = 0.002). The median increment in SCIM III total score was 7 (p = 0.001). The improvements in bladder and bowel management as well as moderate distance mobility subscales were also significant (p < 0.05). Total IANR-SCIFRS scores changed from 17 to 32, which was statistically significant (p = 0.001); again the bladder and bowel management subscale improvements were statistically significant (p < 0.05). Mild side effects of the G-CSF treatment such as bone pain, rash, fever, neuropathic pain, and spasticity were noted in a few patients; all of them resolved after 1 week. Our results indicate that G-CSF administration is a safe process and is associated with neurological as well as functional improvement. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Key words: Granulocyte colony-stimulating factor (G-CSF); Neuroprotective therapy; Spinal cord injury (SCI); Rehabilitation

Received December 26, 2012; final acceptance August 13, 2013. Online prepub date: August 29, 2013.
Address correspondence to Hooshang Saberi, M.D., M.P.H., Brain and Spinal Injury Research Center (BASIR), Imam Khomeini Hospital Complex, Keshavarz Boulevard, P.O. Box 14185-61, Tehran, Iran. Tel: +98 21 66581560; Fax: +98 21 66938885; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it