Cell Medicine 6(3) Abstracts

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Cell Medicine, Vol. 6, pp. 99–109, 2014
2155-1790/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517913X672254
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Autologous Skeletal Myoblast Sheet Therapy for Porcine Myocardial Infarction Without Increasing Risk of Arrhythmia

Yutaka Terajima,*† Tatsuya Shimizu,* Shinpei Tsuruyama,* Hidekazu Sekine,* Hikaru Ishii,‡ Kenji Yamazaki,‡ Nobuhisa Hagiwara,† and Teruo Okano*

*Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, TWIns, Tokyo, Japan
†Department of Cardiology, Tokyo Women’s Medical University, Tokyo, Japan
‡Department of Cardiovascular Surgery, Tokyo Women’s Medical University, Tokyo, Japan

Safety concerns of ventricular tachyarrhythmia have arisen from some clinical trials of autologous skeletal myoblast (SkM) injection therapy. This study examined the effect and safety of SkM sheet therapy in a pig model of chronic myocardial infarction. Minipigs underwent LAD occlusion using a balloon catheter for 2 h, followed by reperfusion. After 28 days, 12 SkM sheets were transplanted onto the infarcted myocardium (sheet group n = 8); the same number of cells was also injected into the myocardium (injection group n = 7), and sham operations were performed as a control (sham group n = 7). Implantable ECG loop recorders (ILR) were placed subcutaneously on the left thorax. At 28 days after transplantation, we assessed cardiac function with MDCT, interrogated ILR, and performed programmed ventricular stimulation (PVS), after which organs were harvested for histopathology. To assess the inflammatory and injury response, inflammation factors and high-sensitive CRP and troponin I were measured at 1, 3, 7, and 28 days after transplantation by the cytokine array method and ELISA, respectively. The sheet group showed an improvement in cardiac function compared with both the injection and sham groups (LVEF change: 5.8 ± 2.7%, −1.0 ± 2.6%, and −3.8 ± 1.8% in the sheet, injection, and sham groups, respectively, p < 0.05). VF was not detected in any group using ILR, while VT was detected in one pig from the injection group. VF was induced in 25.0%, 71.4%, and 28.6% of animals in the sheet, injection, and sham groups, respectively. In the injection group, anti-macrophage-positive cells were observed around the injected cells within the myocardium. Transmission electron microscopic images showed differentiated myofilaments, collagen layers, and a characteristic extracellular matrix surrounding the SkMs in the sheet group. Toroponin I and IL-6 levels were higher in the injection group compared with both the sheet and sham groups. SkM sheets transplanted onto infarcted myocardium improved cardiac function over SkM injection without increasing arrhythmogenicity.

Key words: Cell sheet; Heart failure; Regeneration therapy; Tissue engineering

Received February 21, 2013; final acceptance September 29, 2013. Online prepub date: October 21, 2013.
Address correspondence to Teruo Okano, Ph.D., Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University (TWIns), 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Tel: +81-3-3353-8111, ext. 66201; Fax: +81-3-3359-6046; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 6, pp. 111–122, 2014
2155-1790/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517913X672263
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Estrogen Replacement Therapy for Stroke

Mibel Pabon, Cyrus Tamboli, Sarosh Tamboli, Sandra Acosta, Ike De La Pena, Paul R. Sanberg, Naoki Tajiri, Yuji Kaneko, and Cesar V. Borlongan

Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA

Stroke is the third most common cause of death and severe disability among Western populations. Overall, the incidence of stroke is uniformly higher in men than in women. Stroke is rare in women during the reproductive years and rapidly increases after menopause, strongly suggesting that estrogen (E2) plays an important role in the prevention of stroke. Ongoing studies are currently evaluating both the benefits and the risks associated with E2 replacement therapy and hormone replacement therapy in stroke. Equally important is the role of E2 receptor (ER), as studies indicate that ER populations in several tissue sites may significantly change during stress and aging. Such changes may affect the patient’s susceptibility to neurological disorders including stroke and greatly affect the response to selective E2 receptor modulators (SERMs). Replacement therapies may be inefficient with low ER levels. The goal of this review paper is to discuss an animal model that will allow investigations of the potential therapeutic effects of E2 and its derivatives in stroke. We hypothesize that E2 neuroprotection is, in part, receptor mediated. This hypothesis is a proof-of-principle approach to demonstrate a role for specific ER subtypes in E2 neuroprotection. To accomplish this, we use a retroviral-mediated gene transfer strategy that expresses subtypes of the ER gene in regions of the rat brain most susceptible to neuronal damage, namely, the striatum and the cortex. The animal model is exposed to experimental stroke conditions involving middle cerebral artery occlusion (MCAo) method, and eventually the extent of neuronal damage will be evaluated. A reduction in neuronal damage is expected when E2 is administered with specific ER subtypes. From this animal model, an optimal E2 dose and treatment regimen can be determined. The animal model can help identify potential E2-like therapeutics in stroke and screen for beneficial or toxic additives present in commercial E2 preparations that are currently available. Such studies will be informative in designing drug therapies for stroke.

Key words: Estrogen; Stroke; Replacement therapy; Estrogen receptor; Neuroprotection; Selective estrogen receptor modulators (SERMs)

Received November 9, 2013; final acceptance November 26, 2013. Online prepub date: December 10, 2013.
Address correspondence to Cesar V. Borlongan, Professor and Director, Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel: +1-813-974-3154; Fax: +1-813-974-3078; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 6, pp. 123–127, 2014
2155-1790/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517913X674144
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Oligodendrocytes Engineered With Migratory Proteins as Effective Graft Source for Cell Transplantation in Multiple Sclerosis

Ike De La Pena, Mibel Pabon, Sandra Acosta, Paul R. Sanberg, Naoki Tajiri, Yuji Kaneko, and Cesar V. Borlongan

Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA

Multiple sclerosis (MS) is characterized by widespread immunomodulatory demyelination of the central nervous system (CNS), resulting in nerve cell dysfunction. Accordingly, treatment strategies have been centered on immunodulation and remyelination, with the former primarily focused on reducing the pathology rather than enhancing myelin repair, which the latter targets. While conceding to the emerging view of heterogeneity in the pathology of MS, which precludes variations in degree of immune response (i.e., inflammation) and demyelination, the concept of enhancing myelin repair is appealing since it is likely to provide both disease-reducing and disease-inhibiting therapeutic approaches to MS. In this regard, we and several others have proposed that cell replacement therapy is an effective strategy to repair the myelin in MS. Here we hypothesize that transplantation of mouse bone marrow-derived oligodendrocytes (BMDOs) and BMDOs transfected with ephrin proteins (BMDO + ephrin), which are known to enhance cell and axonal migratory capacity, may produce therapeutic benefits in animal models of MS.

Key words: Multiple sclerosis (MS); Cell transplantation; Bone marrow-derived oligodendrocytes (BMDOs); BMDO + ephrin

Received November 9, 2013; final acceptance November 22, 2013. Online prepub date: December 10, 2013.
Address correspondence to Cesar V. Borlongan, Professor and Director, Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel: +1-813-974-3154; Fax: +1-813-974-3078; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 6, pp. 129–133, 2014
2155-1790/14 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517913X674153
Copyright © 2014 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Disease and Stem Cell-Based Analysis of the 2013 ASNTR Meeting

David J. Eve

Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA

A wide diversity of subjects are presented at the annual American Society of Neural Therapy and Repair meeting every year, and 2013 was no exception. An insight into the current research trends in regenerative medicine was provided, including studies to elucidate disease mechanisms and the means to treat them. Different methods featured in 2013 included stem cell and tissue transplantation, gene therapy, dietary supplementation, and hydrogels as scaffold systems for the growth of stem cells. Diseases ranged from Parkinson’s disease, spinal cord injury, and stroke to traumatic brain injury, pain, and epilepsy. Traumatic brain injury was an increasingly popular topic, highlighting the concerns of soldiers returning from duty overseas. A number of studies looked at ways to treat or elucidate mechanisms for more than one disorder. The studies including stem cells predominantly involved human-derived cells being transplanted, and the most common recipient of stem cells were rodents. Only one autologous transplant study, which featured mouse bone marrow cells being transplanted into mice for the treatment of stroke, was presented this year. The most popular stem cell studied was the neural stem cell, which in some instances was predifferentiated from induced pluripotent stem cells or embryonic stem cells. Other stem cells included the mesenchymal stem cell and adipose, amniotic fluid, and umbilical cord blood-derived cells. Many studies also looked at more than one stem cell type. Combinational studies, such as gene therapy and transplantation, were also commonly explored as well as studies using fetal ventral mesencephalon or spinal cord tissue rather than stem cells. Numerous studies also featured the use of “drugs”—some naturally derived or naturally occurring as well as drug cocktails. A number of possible treatments, including physical therapy and socialization, were explored for a number of different diseases, as well as reports on the current status of four gene therapy clinical trials for the treatment of Parkinson’s disease. Other studies assessed possible causes of specific disorders. In this way, the ASNTR provides an important snapshot of developments in the field of regenerative medicine.

Key words: Regenerative medicine; Neurodegenerative diseases; Stem cell therapies; Combinational studies/therapies

Received November 9, 2013; final acceptance November 30, 2013. Online prepub date: December 10, 2013.
Address correspondence to David John Eve, Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Tel: +1-813-974-6169; Fax: +1-813-974-3078; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it