Cell Transplantation 23(S1) Abstracts

Return to Cell Transplantation>

Cell Transplantation, Vol. 23,Supplement 1 pp. S5-S17, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684952
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Consensus of Clinical Neurorestorative Progress in Patients With Complete Chronic Spinal Cord Injury

Hongyun Huang,* Tiansheng Sun,† Lin Chen,‡ Gustavo Moviglia,§ Elena Chernykh,¶ Klaus von Wild,# Haluk Deda,** Kyung-Sun Kang,†† Anand Kumar,‡‡ Sang Ryong Jeon,§§ Shaocheng Zhang,¶¶ Giorgio Brunelli,## Albert Bohbot,*** Maria Dolors Soler,††† Jianjun Li,‡‡‡ Alexandre Fogaça Cristante,§§§ Haitao Xi,¶¶¶ Gelu Onose,### Helmut Kern,**** Ugo Carraro,†††† Hooshang Saberi,‡‡‡‡Hari Shanker Sharma,§§§§ Alok Sharma,¶¶¶¶ Xijing He,#### Dafin Muresanu,***** Shiqing Feng,††††† Ali Otom,‡‡‡‡‡ Dajue Wang,§§§§§ Koichi Iwatsu,¶¶¶¶¶ Jike Lu,##### and Adeeb Al-Zoubi******

*Center of Neurorestoratology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
†Department of Orthopedics, Beijing Army General Hospital, Beijing, China
‡Medical Center, Tsinghua University, Beijing, China
§Centro de Investigación en Ingeniería de TejidosTerapia Celular, Universidad Maimónides, Buenos Aires, Argentina
¶Institute of Clinical Immunology, Siberian Division of the Russian Academy of Medical Sciences, Institute of Traumatology and Orthopedics, Novosibirsk, Russia
#Medical Faculty, Westfälische Wilhelms University, Münster, North Rhine-Westphalia, Germany
**Department of Neurosurgery and Neurology, Akay Hospital, Ankara, Turkey
††Adult Stem Cell Research Center, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Korea
‡‡Department of Stem Cells, Lifeline Institute of Regenerative Medicine, Rajiv Gandhi SalaiPerungudi, Chennai, India
§§Department of Neurological Surgery, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, Korea
¶¶Department of Orthopedics, Changhai Hospital, Shanghai, China
##Fondazione Midollo Spinale, Brescia, Italy
***Laboratoire de Recherches sur le LASERPONCTURE, Espace Minerve, France
†††Hospital de NeurorehabilitacióInstitut Guttmann, Camí Can Ruti s/n. Barcelona, Spain
‡‡‡Department of Spinal and Neural Function Reconstruction, China Rehabilitation Research Center, Beijing, China
§§§Institute of Orthopedics and Traumatology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
¶¶¶Department of NeurorestoratologyJingdong Zhongmei Hospital, Yanjiao, Beijing East, China
###The Teaching Emergency Hospital Bagdasar-Arseni (TEHBA), Bucharest, Romania
****Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Department of Physical Medicine and Rehabilitation, Wilhelminenspital Wien, Austria
††††Laboratory of Translational Myology, Department of Biomedical Sciences, University of Padua, Italy
‡‡‡‡Department of Neurosurgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Iran
§§§§Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, Sweden
¶¶¶¶Department of Neurosurgery, LTMG Hospital and LTM Medical College, Mumbai, India
####Second Department of Orthopedics, The Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, China
*****Department of Neurosciences, University of Medicine and Pharmacy “Iuliu Hatieganu,” Cluj-Napoca, Romania
†††††Orthopaedic Department of General Hospital of Tianjin Medical University, Tianjin, China
‡‡‡‡‡Spinal Unit, King Hussein Medical Centre, Amman, Jordan
§§§§§Midlands Centre for Spinal Injuries, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK
¶¶¶¶¶Department of Neurosurgery, Osaka University Medical School, Japan
#####Department of Orthopaedic Surgery, Tarre Hospital, NSW, Australia
******Department of Surgery, University of Illinois College of Medicine, Peoria, IL, USA

Currently, there is a lack of effective therapeutic methods to restore neurological function for chronic complete spinal cord injury (SCI) by conventional treatment. Neurorestorative strategies with positive preclinical results have been translated to the clinic, and some patients have gotten benefits and their quality of life has improved. These strategies include cell therapy, neurostimulation or neuromodulationneuroprosthesisneurotization or nerve bridging, and neurorehabilitation. The aim of this consensus by 31 experts from 20 countries is to show the objective evidence of clinical neurorestoration for chronic complete SCI by the mentioned neurorestorative strategies. Complete chronic SCI patients are no longer told, “nothing can be done.” The clinical translation of more effective preclinical neurorestorative strategies should be encouraged as fast as possible in order to benefit patients with incurable CNS diseases. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Consensus; Clinical neurorestorationComplete chronic spinal cord injury; Translational neuroscience; Neurorestoratology

Received January 25, 2014; final acceptance August 21, 2014. Online prepub date October 9, 2014
Address correspondence to Hongyun Huang, Center of Neurorestoratology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China. Tel: +86-13910116608; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S19-S23, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684943
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Comparison of Neurological and Functional Outcomes After Administration of Granulocyte-Colony-Stimulating Factor in Motor-Complete Versus Motor-Incomplete Postrehabilitated, Chronic Spinal Cord Injuries: A Phase I/II Study

Hooshang Saberi,*† Nazi Derakhshanrad,* and Mir Saeed Yekaninejad*‡

*Brain and Spinal Injuries Research Center (BASIR), 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 disease conditions over many years. The administration of the growth factors in spinal cord injury (SCI) has been reported elsewhere; here we have tried to see the effect of SCI severity on the neurological outcomes after neuroprotective treatment for SCI with G-CSF. Seventy-four consecutive patients with SCI of at least 6 months’ duration, with stable neurological status in the last 3 months, having informed consent for the treatment were included in the study. All the patients had undergone at least 3 months of standard rehabilitation. Patients were assessed by the American Spinal Injury Association (ASIA) scale, Spinal Cord Independence Measure (SCIM) III, and International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) just before intervention and periodically until 6 months after subcutaneous administration of 5 μg/kg per day of G-CSF for 7 consecutive days. Multiple linear regression models were performed for statistical evaluation of lesion completeness and level of injury on changes in ASIA motor, light touch, pinprick, IANR-SCIFRS, and SCIM III scores, as a phase I/II comparative study. The study consisted of 52 motor-complete and 22 motor-incomplete SCI patients. There was no significant difference regarding age and sex, chronicity, and level of SCI between the two groups. Motor-incomplete patients had significantly more improvement in ASIA motor score compared to the motor-complete patients (7.68 scores, p < 0.001); also they had significant improvement in light touch (6.42 scores, p = 0.003) and pinprick sensory scores (4.89 scores, p = 0.011). Therefore, G-CSF administration in motor-incomplete SCIs is associated with significantly higher motor improvement, and also the higher the initial ASIA Impairment Scale (AIS) grade, the less would be the final AIS change, and incomplete cases are more welcome into the future studies. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Spinal cord injury (SCI); Granulocyte-colony-stimulating factor (G-CSF); Neurological restoration

Received January 25, 2014; final acceptance August 5, 2014. Online prepub date: October 9, 2014.
Address correspondence to Hooshang Saberi, M.D., M.P.H., Brain and Spinal Injuries Research Center, Imam Khomeini Hospital Complex, Keshavarz Boulevard, Postal 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


Cell Transplantation, Vol. 23,Supplement 1 pp. S25-S34, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684899
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Transplantation of Purified Autologous Leukapheresis-Derived CD34+ and CD133+ Stem Cells for Patients With Chronic Spinal Cord Injuries: Long-Term Evaluation of Safety and Efficacy

Adeeb Al-Zoubi,*† Emad Jafar,‡ Mohammad Jamous,§ Feras Al-Twal,¶ Sameh Al-Bakheet,† Mahasen Zalloum,† Farah Khalifeh,† Samer Abu Radi,# Mohammed El-Khateeb,** and Ziad Al-Zoubi

*Department of Surgery, University of Illinois College of Medicine at Peoria, Peoria, IL, USA
†Stem Cells of Arabia, Amman, Jordan
‡Jordan Orthopedic and Spinal Center, Al-Saif Medical Center, Amman, Jordan
§Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
¶Department of Biology, College of Arts and Sciences, Bradley University, Peoria, IL, USA
#Bone Marrow Transplantation Unit, Al-Khaldi Medical Center, Amman, Jordan
**National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan

This study is aimed at describing a novel method for treating patients with chronic complete spinal cord injuries (SCIs) by utilizing autologous, purified CD34+
and CD133+ stem cells (SCs). The study focuses on the safety and efficacy of transplantingunmanipulatedautologous, purified stem cells in treated patients during a 5-year follow-up period. In this report, 19 patients were included (16 males and 3 females) who presented with a complete SCI (ASIA-A) in the thoracic region. The patients’ endogenous cells were mobilized with subcutaneous granulocyte-colony-stimulating factor (G-CSF) for 5 days. We utilized the CliniMACS magnetic separation system to purify leukapheresis-derived CD34+ and CD133+ SCs. Purified SCs were directly transplanted into the SCI site. Patients were then monitored and followed for up to 5 years. On average, 76 × 106 purified SCs were obtained from each patient, with 95.2% purity and >98% viability. SC transplantation into the cyst cavity or the subarachnoid space was successful and well tolerated in all 19 patients and did not cause any allergic or inflammatory reactions within the CNS in the early or late periods after transplantation. Ten patients (53%) showed no improvement after 42–60 months (ASIA-A), while seven patients (37%) demonstrated segmental sensory improvement (ASIA-B), and the remaining two patients (10%) had motor improvement (ASIA-C). This study presents a safe method for transplanting specific populations of purified autologous SCs that can be used to treat SCIs in a clinical setting. The results may be utilized as a stepping-stone for future investigations in the field of regenerative medicine for treatment of SCIs and other neurological diseases. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: CD133; CD34; Stem cell transplantation; Leukapheresis; Spinal cord injury (SCI); CliniMACS

Received January 25, 2014; final acceptance August 29, 2014. Online prepub date: November 4, 2014.
Address correspondence to Adeeb Al-Zoubi, 246 Al-Medina Al-Munawara St., Amman, Jordan (11953). Tel: +9625692111; Fax: +9625692114; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S35-S44, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X685014
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

A Prospective Randomized Double-Blind Clinical Trial Using a Combination of Olfactory Ensheathing Cells and Schwann Cells for the Treatment of Chronic Complete Spinal Cord Injuries

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

*Center of Neurorestoratology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
†Beijing Hongtianji Neuroscience Academy, Beijing, China
‡Medical Center, Tshinghua University, Beijing, China

The aim of this prospective randomized double-blind clinical study is to examine the benefits of using olfactory ensheathing cells (OECs) combined with or without Schwann cells (SCs) in treating chronic complete spinal cord injuries (SCIs). This would offer patients a better alternative for neurological functional recovery. According to the initial design, 28 eligible participants with cervical chronic complete SCI were recruited and randomly allocated into four groups of seven participants each. The neurological assessments were to be performed according to the American Spinal Injury Association (ASIA) and International Association of Neurorestoratology (IANR) Functional Rating Scales, in combination with electrophysiological tests, for example, electromyography (EMG) and paraspinal somatosensory evoked potentials (PSSEPs). Here we have summarized the data from seven patients; three patients received an OEC intraspinal transplantation, one underwent SC implantation, and one received a combination of OECs and SCs. The remaining two patients were used as controls. The scores were evaluated independently by at least two neurologists in a blinded fashion for comparing the neurological functional changes during pre- and post-cell transplantation (6-month follow-up). All patients who received OECs, SCs alone, and a combination of them showed functional improvement. Mild fever occurred in one of the patients with OEC transplant that subsided after symptomatic treatments. All treated patients except one showed improvement in the electrophysiological tests. The functional improvement rate comprises 5/5 (100%) in the treated group, but 0/2 (0%) in the control group (p = 0.008). These preliminary findings show that transplanting OECs, SCs, or a combination of them is well tolerated and that they have beneficial effects in patients. Thus, further studies in larger patient cohorts are warranted to assess the benefits and risks of these intervention strategies. This manuscript is published as part of the IANR special issue of Cell Transplantation.

Key words: Olfactory ensheathing cells (OECs); Schwann cells (SCs); Spinal cord injury (SCI); Transplantation; Clinical trial

Received March 12, 2014; final acceptance October 9, 2014. Online prepub date: October 20, 2014.
Address correspondence to Hongyun Huang, M.D., Ph.D., Center of Neurorestoratology, Beijing Rehabilitation Hospital, 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. 23,Supplement 1 pp. S45-S56, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684989
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Neural Stem Cell-Conditioned Medium Protects Neurons and Promotes Propriospinal Neurons Relay Neural Circuit Reconnection After Spinal Cord Injury

Peng Liang,* Jiaren Liu,† Jinsheng Xiong,* Qing Liu,* Jiaxin Zhao,* Hongsheng Liang,* Liwei Zhao,* and Haitao Tang*

*Harbin Medical University Cancer Hospital, Harbin, China
†Children’s Hospital Boston, Harvard Medical University, Boston, MA, USA

Human fetal neural stem cells (hNSCs) are used to treat a variety of neurological disorders involving spinal cord injury (SCI). Although their mechanism of action has been attributed to cell substitution, we examined the possibility that NSCs may haveneuroprotective activities. The present article studied the action of hNSCs on protecting neurons and promoting corticospinal tract (CST) axon regeneration after SCI. hNSCs were isolated from the cortical tissue of spontaneously aborted human fetuses. The cells were removed from the NSC culture medium to acquire NSCM, thus excluding the effect of cell substitution. Continuous administration of the NSCM after the SCI resulted in extensive growth of the CST in the cervical region and more than tripled the formation of synaptic contacts between CST collaterals and propriospinal interneurons that project from the cervical level of the spinal cord to the lumbar level. NSCM reduced the number of caspase 3-positive apoptotic profiles at 7 days and protected against loss of the neurons 6 weeks after injury. NSCM promoted locomotor recovery with a five-point improvement on the BBB scale in adult rats. Thus, hNSCs help to set up a contour neural circuit via secretory factors, which may be the mechanism for their action in SCI rats. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Spinal cord injury (SCI); Neural stem cells (NSCs); Neuron; Transplantation

Received January 25, 2014; final acceptance October 12, 2014. Online prepub date: October 20, 2014.
Address correspondence to Dr. Peng Liang, M.D., Ph.D., Department of Neurosurgery, Harbin Medical University Cancer Hospital, No. 154 Heping Road, Harbin 150086, China. Tel: +86-13936620157; Fax: +86-451-86298836; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S57-S64, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684934
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Intra-Arterial Bone Marrow Mononuclear Cell Transplantation Correlates With GM-CSF, PDGF-BB, and MMP-2 Serum Levels in Stroke Patients: Results From a Clinical Trial

Francisco Moniche,* Joan Montaner,†‡ Jose-Ramon Gonzalez-Marcos,* Magdalena Carmona,§ Pilar Piñero,¶ Ildefonso Espigado,§ Aurelio Cayuela,# Irene Escudero,* Francisco-Javier de la Torre-Laviana,* Cristina Boada,‡ Anna Rosell,‡ Antonio Mayol,¶ Maria-Dolores Jimenez,* Alberto Gil-Peralta,* and Alejandro Gonzalez¶

*Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain
Instituto de Biomedicina de Sevilla-IBiS, Hospital Universitario Virgen del Rocío, Seville, Spain
‡Neurovascular Research Laboratory, Institut de Recerca Valld’Hebron, Hospital Valld’Hebron, Barcelona, Spain
§Department of Hematology, Hospital Universitario Virgen del Rocío, Seville, Spain
¶Department of Radiology, Hospital Universitario Virgen del Rocío, Seville, Spain
#Clinical Research Services, Hospital Universitario Virgen del Rocío, Seville, Spain

Bone marrow mononuclear cell (BM-MNC) intra-arterial transplantation improves recovery in experimental models of ischemic stroke through secretion of cytokines and growth factors (GFs), enhancing neoangiogenesis, and enhancing neuroplasticity. In this study, we tested whether BM-MNC transplantation in stroke patients induces changes in serum levels of cytokines and GFs. A phase I/II trial was conducted in middle cerebral artery (MCA) stroke patients with autologous intra-arterial BM-MNC transplantation between 5 and 9 days after stroke. Follow-up was done for up to 6 months. Eight cases and nine controls were included, and the serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), β nerve growth factor (β-NGF), and matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) were measured before and 4, 8, and 90 days after transplantation. The correlation of these serum levels with dose of cells and clinical outcomes was studied. A total of 1.59 × 108
(±1.21 × 108) BM-MNCs were injected in cases; of them 3.38 × 106 (±2.33 × 106) were CD34+ cells. There was a positive correlation between total BM-MNCs injected and levels of GM-CSF and PDGF-BB at 90 days after transplantation (r = 0.929, p = 0.001 and r = 0.714, p = 0.047, respectively), and a negative correlation between total CD34+ cells injected and MMP-2 levels at 4 days after transplantation (r = −0.786, p = 0.036). Lower plasma levels of MMP-2 at 4 days and higher levels of PDGF-BB at 90 days were associated with better functional outcomes during follow-up (p = 0.019 and p = 0.037, respectively). When administered intra-arterially in subacute MCA stroke patients, BM-MNCs seem to induce changes in serum levels of GM-CSF, PDGF-BB, and MMP-2, even 3 months after transplantation, which could be associated with better functional outcomes. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue ofCell Transplantation.

Key words: Stroke; Stem cells; Growth factors (GFs); Cell transplantation

Received January 25, 2014; final acceptance October 8, 2014. Online prepub date: October 20, 2014.
Address correspondence to Francisco Moniche, M.D., Ph.D., Neurology Department, Hospital Universitario Virgen del RocíoAvda. Manuel Siurot s/n. Seville 41013, Spain. Tel: +34 955012593; Fax: +34 955012597; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S65-S72, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684961
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

A Two-Year Follow-Up Study of Cotransplantation With Neural Stem/Progenitor Cells and Mesenchymal Stromal Cells in Ischemic Stroke Patients

Li-yan Qiao,* Fang-jie Huang,* Mangsuo Zhao,* Jing-hui Xie,* Jie Shi,* Jing Wang,* Xian-zhong Lin,* Huancong Zuo,† Yun-liang Wang,‡ and Tong-chao Geng*

*Department of Neurology, Yuquan Hospital of Tsinghua University, Beijing, China
†Department of Neurosurgery, Yuquan Hospital of Tsinghua University, Beijing, China
‡Department of Neurology, 148 Hospital of PLA, Zibo, Shandong Province, China

Stem cell therapy is an emerging therapeutic modality in the treatment of stroke. We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells (NSPCs) and mesenchymal stromal cells (MSCs) in patients with ischemic stroke. Eight patients were enrolled in this study. All patients had a hemisphere with infarct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging (MRI). The patients received one of the following two types of treatment: the first treatment involved four intravenous injections of MSCs at 0.5 × 106/kg body weight; the second treatment involved one intravenous injection of MSCs at 0.5 × 106/kg weight followed by three injections of MSCs at 5 × 106/patient and NSPCs at 6 × 106/patient through the cerebellomedullary cistern. The patients’ clinical statuses were evaluated with the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel index (BI). Six patients were given four cell transplantations. The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2–4 days after each therapy. One patient exhibited minor dizziness. All side effects appeared within the first 2–24 h of cell transplantation, and they resolved without special treatment. There was no evidence of neurological deterioration or neurological infection. Most importantly, no tumorigenesis was found at a 2-year follow-up. The neurological functions, disability levels, and daily living abilities of the patients in this study were improved. While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function, further studies that include larger samples, longer follow-ups, and control groups are still needed. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Neural stem/progenitor cells (NSPCs); Mesenchymal stromal cells (MSCs); Ischemic stroke; Cell transplantation

Received January 25, 2014; final acceptance October 8, 2014. Online prepub date: October 20, 2014.
Address correspondence to Tong-chao Geng, Department of Neurology, Yuquan Hospital of Tsinghua University, Beijing, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Yunliang Wang, Department of Neurology, 148 Hospital of PLA, Zibo, Shandong Province, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S73-S82, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X685023
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Intra-Arterial Delivery of Human Bone Marrow Mesenchymal Stem Cells Is a Safe and Effective Way to Treat Cerebral Ischemia in Rats

Shiwei Du,*1 Jian Guan,*1 Gengsheng Mao,†1 Yang Liu,* Sihai Ma,* Xinjie Bao,* Jun Gao,* Ming Feng,* Guilin Li,* Wenbin Ma,* Yi Yang,* Robert Chunhua Zhao,‡ and Renzhi Wang*

*Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
†Department of Neurovascular Surgery, General Hospital of Armed Police Forces, Beijing, P. R. China
‡Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China

Cerebral ischemic stroke is a very common condition that can cause death and disability. Studies have confirmed that stem cells have therapeutic effects if administered after a stroke. There is still a great deal of debate regarding the best route for cell transplantation. Intravascular delivery is the most commonly used one. In this study, the therapeutic effects of bone marrow stem cells (BMSCs) delivered by intra-arterial (IA) and intravenous (IV) injection in a rat transient middle cerebral artery occlusion model (MCAO) are compared. Histological analysis demonstrated that the IA route bypasses the pulmonary system and directs the cells to the ischemic parts of the brain more efficiently. The BMSCs delivered via the IA route promoted angiogenesis and improved functional recovery. The cerebral blood flow (CBF) of the rats was monitored during the IA injection process. No reduction in CBF or microstrokes was detected. Brain perfusion and metabolism, as evaluated by SPECT and PET, were better in rats treated with cells delivered via IA. Results showed that the IA route is a safe and effective way to transplant hBMSCs. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Transplantation; Bone marrow; Mesenchymal stem cells; Stroke; Intra-arterial (IA) route

Received March 12, 2014; final acceptance October 3, 2014. Online prepub date: November 4, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Renzhi Wang, Department of Neurosurgery, Peking Union Medical College Hospital, Dongdan, Dong Cheng District, Beijing 100005, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S83-S95, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684998
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Experimental Therapy on Brain Ischemia by Improvement of Local Angiogenesis With Tissue Engineering in the Mouse

Rongkai JuYujun WenRongbin Gou, Ying Wang, and Qunyuan Xu

Department of Neurobiology, Beijing Institute for Brain Disorders, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Capital Medical University, Beijing, China

Neural restoration has proven to be difficult after brain stroke, especially in its chronic stage. This is mainly due to the generation of an unpropitious niche in the injured area, including loss of vascular support but production of numerous inhibitors against neuronal regeneration. Reconstruction of a proper niche for promoting local angiogenesis, therefore, should be a key approach for neural restoration after stroke. In the present study, a new biomaterial composite that could be implanted in the injured area of the brain was created for experimental therapy of brain ischemia in the mouse. This composite was made using a hyaluronic acid (HA)-based biodegradable hydrogel scaffold, mixed with poly(lactic-co-glycolic acid) (PLGA) microspheres containing vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), two factors that stimulate angiogenesis. In addition, the antibody of Nogo receptor (NgR-Ab), which can bind to multiple inhibitory myelin proteins and promote neural regeneration, was covalently attached to the hydrogel, making the hydrogel more bioactive and suitable for neural survival. This composite (HA–PLGA) was implanted into the mouse model with middle cerebral artery occlusion (MCAO) to explore a new approach for restoration of brain function after ischemia. A good survival and proliferation of human umbilical artery endothelial cells (HUAECs) and neural stem cells (NSCs) were seen on the HA hydrogel with PLGA microspheres in vitro. This new material was shown to have good compatibility with the brain tissue and inhibition to gliosis and inflammation after its implantation in the normal or ischemic brain of mice. Particularly, good angiogenesis was found around the implanted HA–PLGA hydrogel, and the mouse models clearly showed a behavioral improvement. The results in this present study indicate, therefore, that the HA–PLGA hydrogel is a promising material, which is able to induce angiogenesis in the ischemic region by releasing VEGF and Ang1, thus creating a suitable niche for neural restoration in later stages of stroke. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Hyaluronic acid (HA) hydrogelPoly(lactic-co-glycolic acid) (PLGA); Neural stem cells (NSCs); Angiogenesis; Ischemic stroke

Received January 25, 2014; final acceptance August 31, 2014. Online prepub date: October 9, 2014.
Address correspondence to Qunyuan Xu, M.D., Ph.D., Department of Neurobiology, Beijing Institute for Brain Disorders, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Capital Medical University, 10 XitoutiaoYouanmen, Beijing 100069, China. Tel and Fax: +86-10-8391-1464; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S97-S104, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684925
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Clinical Experience With Autologous M2 Macrophages in Children With Severe Cerebral Palsy

Elena R. Chernykh, Marina Yu. Kafanova, Ekaterina Ya. Shevela, Sergei I. Sirota, Elena I. Adonina, Lyudmila V. Sakhno, Alexander A. Ostanin, and Vladimir V. Kozlov

Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology of Russian Academy on Medical Sciences, Siberian Branch, Novosibirsk, Russia

Stem cell-based therapy is considered to be a new approach for the treatment of cerebral palsy (CP). Given the potent anti-inflammatory activity and high regenerative potential of M2 macrophages, these cells may be an alternative source for cell transplantation. To evaluate the safety and efficacy of autologous M2 macrophages, we conducted a pilot clinical trial in 21 children with severe CP. The primary outcome measure was safety, which included assessment of mortality of any cause, immediate adverse reactions, and serious adverse effects and comorbidities during 5-year follow-up. The secondary outcome measure was functional improvement in Gross Motor Function Measure (66-item GMFM) test, Peabody Developmental Motor Scale-Fine Motor (PDMS-FM) test, Ashworth scale, MRC scale, and an easy-to-understand questionnaire for evaluation of cognitive functions in our modification. Intradural injection of M2 cells (in mean dose of 0.8 × 106/kg) into the lumbar spinal area did not induce any serious adverse events. No cases of mortality, psychomotor worsening, exacerbation of seizures, and long-term comorbidities, including tumors, were observed during a 5-year follow-up. After 3 months, GMFM score increased from 13.7 ± 7.8 to 58.6 ± 14.6, PDMS-FM score improved from 0.76 ± 0.42 to 5.05 ± 0.97, and the Ashworth score decreased from 3.8 ± 0.21 to 3.3 ± 0.24. Along with gross and fine motor function enhancement, an improvement of cognitive activity (from 1.62 ± 0.41 to 4.05 ± 0.64, according to questionnaire assessment) and reduction of seizure syndrome were registered as well. The neurological improvements did not diminish during the 5-year follow-up period. The data obtained suggest that cell therapy based on M2 macrophages is safe, does not induce early adverse effects and long-term comorbidities, and is accompanied with a significant improvement of motor and cognitive activities in severe CP patients. This manuscript is published as part of the International Association ofNeurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Cerebral palsy (CP); Cell-based therapy; M2 macrophages

Received January 25, 2014; final acceptance August 12, 2014. Online prepub date: October 9, 2014.
Address correspondence to Elena Chernykh, Professor, Head of Laboratory of Cellular Immunotherapy, Institute of Clinical Immunology RAMS SB, Yadrintsevskaya str., 14, Novosibirsk 630099, Russia. Tel: +7(383)2360329; Fax: +7(383)2227028; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S105-S112, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684916
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Efficacy of Fetal Stem Cell Transplantation in Autism Spectrum Disorders: An Open-Labeled Pilot Study

James Jeffrey Bradstreet,* Nataliia Sych,† Nicola Antonucci,‡ Mariya Klunnik,† Olena Ivankova,† Irina Matyashchuk,† Mariya Demchuk,† and Dario Siniscalco‡§¶

*International Child Development Resource Center, Chateau Elan, GA, USA
†Clinical Department, Cell Therapy Center – EmCell, Kyiv, Ukraine
‡Biomedical Centre for Autism Research and Treatment, Bari, Italy
§Centre for Autism – La Forza del Silenzio, Caserta, Italy
Cancellautismo – Nonprofit Association for Autism Care, Florence, Italy

Autism spectrum disorders (ASDs) are heterogeneous complex neurodevelopmental pathologies defined by behavioral symptoms, but which have well-characterized genetic, immunological, and physiological comorbidities. Despite extensive research efforts, there are presently no agreed upon therapeutic approaches for either the core behaviors or the associated comorbidities. In particular, the known autoimmune disorders associated with autism are appealing targets for potential stem cell therapeutics. Of the various stem cell populations, fetal stem cells (FSCs) offer the potent immunoregulatory functions found in primordial mesenchymal stem cells, while exhibiting rapid expansion capacity and recognized plasticity. These properties enhance their potential for clinical use. Furthermore, FSCs are potent and implantable “biopharmacies” capable of delivering trophic signals to the host, which could influence brain development. This study investigated the safety and efficacy of FSC transplantations in treating children diagnosed with ASDs. Subjects were monitored at pre, and then 6 and 12 months following the transplantations, which consisted of two doses of intravenously and subcutaneously administered FSCs. The Autism Treatment Evaluation Checklist (ATEC) test and Aberrant Behavior Checklist (ABC) scores were performed. Laboratory examinations and clinical assessment of adverse effects were performed in order to evaluate treatment safety. No adverse events of significance were observed in ASD children treated with FSCs, including no transmitted infections or immunological complications. Statistically significant differences (p < 0.05) were shown on ATEC/ABC scores for the domains of speech, sociability, sensory, and overall health, as well as reductions in the total scores when compared to pretreatment values. We recognize that the use of FSCs remains controversial for the present. The results of this study, however, warrant additional investigations into the mechanisms of cell therapies for ASDs, while prompting the exploration of FSCs as “biopharmacies” capable of manufacturing the full array of cell-signaling chemistry. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key Words: Autism; Fetal stem cells; Transplantation; Cell therapy; Biopharmacy

Received January 25, 2014; final acceptance September 8, 2014. Online prepub date: October 9, 2014.
Address correspondence to Dario SiniscalcoChem.D., Ph.D., Department of Experimental Medicine, Second University of Naples via S. Maria di Costantinopoli 16 80138 Naples, Italy. Tel: +39 (0)81 5667532 (lab), +39 (0)81 5665880 (office); Fax: +39 (0)81 5667503; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S113-S122, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X685005
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Potential of Human Umbilical Cord-Derived Mesenchymal Stem Cells as a Novel Cellular Therapy for Multiple Sclerosis

Jin-Feng Li,*†1 Da-Jin Zhang,‡1 Tongchao Geng,§ Lin Chen,§ Hongyun Huang,¶ Hong-Lei Yin,* Yu-zhen Zhang,* Ji-Yu Lou,# Bingzhen Cao,† and Yun-Liang Wang*#

*The Neurology Department of the 148th Hospital, Zibo, P. R. China
†General Hospital of Jinan Military Region, Jinan, P. R. China
‡Medical Research Center of Naval General Hospital, Beijing, P. R. China
§Second Affiliated Hospital of Tsinghua University, Beijing, P. R. China
¶Beijing Hongtianji Neuroscience Academy, Beijing, P. R. China
#The Neurology Department of The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China

Multiple sclerosis (MS) is a complex disease of neurological disability, affecting more than 300 out of every 1 million people in the world. The purpose of the study was to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation in MS patients. Twenty-three patients were enrolled in this study, and 13 of them were given hUC-MSC therapy at the same time as anti-inflammatory treatment, whereas the control patients received the anti-inflammatory treatment only. Treatment schedule included 1,000 mg/kg of methylprednisolone intravenously (IV) daily for 3 days and then 500 mg/kg for 2 days, followed by oral prednisone 1 mg/kg/day for 10 days. The dosage of prednisone was then reduced by 5 mg every 2 weeks until reaching a 5-mg/day maintenance dosage. Intravenous infusion of hUC-MSCs was applied three times in a 6-week period for each patient. The overall symptoms of the hUC-MSC-treated patients improved compared to patients in the control group. Both the EDSS scores and relapse occurrence were significantly lower than those of the control patients. Inflammatory cytokines were assessed, and the data demonstrated a shift from Th1 to Th2 immunity in hUC-MSC-treated patients. Our data demonstrated a high potential for hUC-MSC treatment of MS. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Multiple sclerosis (MS); Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs); Stem cell transplantation; Cytokine; Th1 immunity: Th2 immunity

Received January 25, 2014; final acceptance October 31, 2014. Online prepub date: November 5, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Bingzhen Cao, General Hospital of Jinan Military Region, 25 Shifan Road, Jinan 250031, P. R. China. Tel: +86 533-6552100; Fax: +86 533-6552137; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Yun-Liang Wang, The Neurology Department of the 148th Hospital, 20 Zhanbei Road, Zibo 255300, P. R. China. Tel: +86 533-6552100; Fax: +86 533-6552137; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S123-S139, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684970
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Intranasal Delivery of Bone Marrow-Derived Mesenchymal Stem Cells, Macrophages, and Microglia to the Brain in Mouse Models of Alzheimer’s and Parkinson’s Disease

Lusine Danielyan,* Sandra Beer-Hammer,† Alexandra Stolzing,‡ Richard Schäfer,§¶ Georg Siegel,¶ Claire Fabian,‡ Philipp Kahle,# Tilo Biedermann,** Ali Lourhmati,* Marine Buadze,* Ana Novakovic,† Barbara Proksch,* Christoph H. Gleiter,* William H. Frey II,†† and Matthias Schwab*‡‡

*Department of Clinical Pharmacology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, University of TübingenTübingen, Germany
†Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, University ofTübingenTübingen, Germany
‡Department of Cell Therapy Stem Cell Biology and Regeneration Unit, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
§Department Cell Therapeutics and Cell Processing, Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hesse gGmbH, Johann Wolfgang Goethe University Hospital, Frankfurt, Germany
¶Institute for Clinical and Experimental Transfusion Medicine (IKET,) University Hospital of TübingenTübingen, Germany
#Department of NeurodegenerationHertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Faculty of Medicine, University of TübingenTübingen, Germany
**Department of Dermatology, Eberhard Karls University TübingenTübingen, Germany
††Alzheimer’s Research Center, HealthPartners Center for Memory and Aging, Regions Hospital, St. Paul, MN, USA
‡‡Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany

In view of the rapid preclinical development of cell-based therapies for neurodegenerative disorders, traumatic brain injury, and tumors, the safe and efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSCs) to the brain in the rat 6-hydroxydopamine model of Parkinson’s disease (PD). The present study examined delivery of bone marrow-derived MSCs, macrophages, and microglia to the brain in a transgenic model of PD [(Thy1)-h[A30P] αS] and an APP/PS1 model of Alzheimer’s disease (AD) via intranasal application (INA). INA of microglia in naive BL/6 mice led to targeted and effective delivery of cells to the brain. Quantitative PCR analysis of eGFP DNA showed that the brain contained the highest amount of eGFP-microglia (up to 2.1 × 104) after INA of 1 × 106
cells, while the total amount of cells detected in peripheral organs did not exceed 3.4 × 103. Seven days after INA, MSCs expressing eGFP were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem of (Thy1)-h[A30P] αStransgenic mice, showing predominant distribution within the OB and brainstem. INA of eGFP-expressing macrophages in 13-month-old APP/PS1 mice led to delivery of cells to the OB, hippocampus, cortex, and cerebellum. Both MSCs and macrophages contained Iba-1-positive population of small microglia-like cells and Iba-1-negative large rounded cells showing either intracellular amyloid β (macrophages in APP/PS1 model) or α-synuclein [MSCs in (Thy1)-h[A30P] αS model] immunoreactivity. Here, we show, for the first time, intranasal delivery of cells to the brain of transgenic PD and AD mouse models. Additional work is needed to determine the optimal dosage (single treatment regimen or repeated administrations) to achieve functional improvement in these mouse models with intranasal microglia/macrophages and MSCs. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Intranasal; Mesenchymal stem cells (MSCs); Macrophages; Alzheimer’s disease; Parkinson’s disease; Amyloid beta ()

Received January 25, 2014; final acceptance September 24, 2014. Online prepub date: October 9, 2014.
Address correspondence to Lusine Danielyan, Department of Clinical Pharmacology, Eberhard Karls University Hospitals and Clinics and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany. Tel: +49 (0) 70712974926; Fax: +49 (0) 7071295035; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 23,Supplement 1 pp. S141-S150, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X685032
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

First Study of Intra-Arterial Delivery of Myogenic Mononuclear Cells to Skeletal Muscles in Primates

Daniel Skuk and Jacques P. Tremblay

Neurosciences Division–Human Genetics, CHUQ Research Center–CHUL, Quebec, QC, Canada

The main challenge of cell transplantation as a treatment of myopathies is the large amount of tissue to treat. Intravascular delivery of cells may be an ideal route if proven to be effective and safe. Given the importance of nonhuman primates for preclinical research in transplantation, we tested the intra-arterial injection of β-galactosidase (β-Gal)-labeled myoblasts in macaques. Cells were injected into one of the femoral arteries in seven monkeys. Some muscle sites were damaged concomitantly in three monkeys. Various organs and muscles were sampled 1 h, 1 day, 12 days, 3 weeks, and 5 weeks after transplantation. Samples were analyzed by histology. Most β-Gal+
cells were observed in the capillaries and arterioles of muscles and other tissues of the leghomolateral to the cell injection. Groups of necrotic myofibers in the proximity of an arteriole plugged by a β-Gal+ embolus were interpreted as microinfarcts. Scarce β-Gal+ cells were observed in the lungs 1 h and 1 day posttransplantation. No β-Gal+ cells were observed in other organs or muscles. β-Gal+ myofibers were observed 12 days, 3 weeks, and 5 weeks after transplantation in muscles of the leg after the cell injection, in sites that were damaged at the time of cell injection. In conclusion, most intra-arterially injected myoblasts were retained in vessels of the leg homolateral to the cell injection site, and they fused with myofibers in regions in which there was a process of myofiber regeneration. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Intra-arterial injection; Myogenic cell transplantation; Myoblast; Nonhuman primate; Skeletal muscle

Received March 12, 2014; final acceptance September 2, 2014. Online prepub date: October 9, 2014.
Address correspondence to Daniel Skuk, M.D., Unité de recherche en Génétique humaine, P-09300, CHUL, 2705 boulevard Laurier, Québec (QC), G1V 4G2, Canada. Tel: +1 (418) 654-2186; Fax: +1 (418) 654-2207; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it



Cell Transplantation, Vol. 23,Supplement 1 pp. S151-S170, 2014
0963-6897/14 $90.00
+ .00
DOI: http://dx.doi.org/10.3727/096368914X684907
E-ISSN 1555-3892
Copyright ©
2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

To the Novel Paradigm of Proteome-Based Cell Therapy of Tumors: Through Comparative Proteome Mapping of Tumor Stem Cells and Tissue-Specific Stem Cells of Humans

Andrey Bryukhovetskiy,*† Valeriy Shevchenko,‡ Sergey Kovalev,‡ Vladimir Chekhonin,§ Vladimir Baklaushev,§ Igor Bryukhovetskiy,¶ and Maria Zhukova

*Federal Research Center for Specialized Types of Medical Assistance and Medical Technologies of FMBA of Russia, Moscow, Russia
NeuroVita Clinic of Restorative and Interventional Neurology and Therapy, Moscow, Russia
‡FGBU Blokhin Russian Cancer Research Center of RAMN, Moscow, Russia
§FGBU Serbski State Research Center of Social and Forensic Psychiatry, Moscow, Russia
¶School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation

We performed proteome mapping (PM), cataloging, and bioinformation analysis of protein lysates of human neural (CD133
+) progenitor and stem cells (NPSCs) isolated from the olfactory sheath of a nose, multipotent mesenchymal (CD29+, CD44+, CD73+, CD90+, CD34stromal cells (MMSCs) isolated from human bone marrow, and tumor (CD133+) stem cells (TSCs) isolated from the human U87 glioblastoma (GB) cell line. We identified 1,664 proteins in the examined lysates of stem cells (SCs), 1,052 (63.2%) of which are identical in NPSCs and TSCs and 607 proteins (36.47%) of which are identical in MMSCs and TSCs. Other proteins in U87 GB TSCs are oncospecific or carcinogenesis associated. The biological processes, molecular functions, cell localization, and protein signal pathways of the proteins available in all three proteomes were annotated by PubMed (http://www.ncbi.nlm.nih.gov/pubmed/), PANTHER (http://www.pantherdb.org/), GeneOntology (http://www.geneontology.org/), and KEGG (http://www.genome.jp/kegg/) databases. It was shown that gliomaspheres of U87 GB had only 10 intracellular signal transduction pathways (ISTP) that were not modified by the neoplastic process, but only two of them (integrin and focal adhesion pathways) were accessible for regulatory action on gene candidates in the TSC nucleus. Carcinogenesis-free membrane proteins, IPST, and genes expressing proteins of these pathways in U87 GB TSCs can be viewed as main targets for regulatory effects on TSCs. We offer a novel concept of proteome-based complex therapy of tumors. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Key words: Neural stem cells; Mesenchymal stem cells; Tumor stem cells (TSCs); U87 glioblastoma; Proteome mapping (PM); Proteome-based therapy of tumors

Received January 25, 2014; final acceptance September 24, 2014. Online prepub date: October 9, 2014.
Address correspondence to Maria V. ZhukovaNeuroVita Clinic of Restorative and Interventional Neurology and Therapy, 23 Kashirskoe shosse, 115478 Moscow, Russia. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it