Cell Medicine 1(2-3) Abstracts

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Volume 1, Number 3

Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 115–122, 2010
2155-1790/10 $90.00 + .00
DOI: 10.3727/215517910X551044
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Autografting of Renal Progenitor Cells Ameliorates Kidney Damage in Experimental Model of Pyelonephritis

Abdol-Mohammad Kajbafzadeh,* Azadeh Elmi,* Saman Shafaat Talab,* Zhina Sadeghi,* Hamed Emami,* and Masoud Sotoudeh†

*Pediatric Urology Research Center, Children’s Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran
†Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Current therapies for pyelonephritic renal damage have severe limitations; stem cells may offer an exciting potential in regenerating nephrology. We aimed to investigate the feasibility of direct intrarenal injection of autologous renal progenitor cells (RPCs; originated from epithelial cells in Bowman’s capsule) in chronic pyelonephritis rat model. Twenty-seven rats were divided into three groups. The control group (GI, n = 3) underwent sham subcapsular injection of isotonic saline. Pyelonephritis was induced in the right kidney of the remaining 24 rats and isotonic saline (GII, n = 12) or labeled autologous RPCs, obtained from a biopsy of left kidney (GIII, n = 12), were injected into the subcapsular space 6 weeks later. At 7, 14, 28, and 60 days, dimercaptosuccinic acid scan was performed in three animals of each group at every interval and subsequently renal sections were obtained for the evaluation of tubular and glomerular regeneration and proliferation. Cell transplantation resulted in the reduction of tubular and glomerular atrophy after 2 weeks. The transplanted cells were observed in the reconstructed region of the kidneys as evidenced by the presence of fluorescently labeled cells both in tubules and glomeruli. We also observed significant decrease in interstitial fibrosis in the fourth week and there were higher amount of Ki-67-positive cells in GIII. Notably, the right renal tissue integrity was significantly improved in this group and revealed normal cortical function on day 60. Transplanting RPCs showed the potential for partial augmentation of kidney structure and function in pyelonephritis. Cellular repair was seen predominantly in the proximal tubule, the major site of injury in pyelonephritis. Our findings may pave the way toward the future regeneration of renal scarring of pyelonephritis in children.

Key words: Pyelonephritis; Renal stem cell; Transplantation

Address correspondence to Abdol-Mohammad Kajbafzadeh, M.D., No. 36, 2nd Floor, 7th Street, Saadat-Abad, Ave. Tehran 1998714616, Iran. Tel: +98 21 2208 9946; Fax: +98 21 2206 9451; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 123–135, 2010
2155-1790/10 $90.00 + .00
DOI: 10.3727/215517910X551053
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Monitoring of Liver Cell Transplantation in a Preclinical Swine Model Using Magnetic Resonance Imaging

Nathanael Raschzok,* Ulf Teichgräber,† Nils Billecke,* Anja Zielinski,* Kirsten Steinz,* Nora N. Kammer,* Mehmet H. Morgul,*‡ Sarah Schmeisser,* Michaela K. Adonopoulou,* Lars Morawietz,§ Bernhard Hiebl,¶ Ruth Schwartlander,# Wolfgang Rüdinger,** Bernd Hamm,† Peter Neuhaus,* and Igor M. Sauer*

*General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin, Berlin, Germany
†Radiology, Charité-Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany
‡Visceral, Transplantation, Thorax, and Vascular Surgery, Universitätsklinikum Leipzig, Leipzig, Germany
§Institute of Pathology, Charité-Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany
¶Centre for Biomaterial Development and Berlin-Brandenburg Centre for Regenerative Therapies (BCRT), Institute for Polymer Research, GKSS Research Centre Geesthacht GmbH, Teltow, Germany
#Department of Materials, ETH Zurich, Zurich, Switzerland
**Cytonet GmbH, Weinheim, Germany

Liver cell transplantation (LCT) is a promising treatment approach for certain liver diseases, but clinical implementation requires methods for noninvasive follow-up. Labeling with superparamagnetic iron oxide particles can enable the detection of cells with magnetic resonance imaging (MRI). We investigated the feasibility of monitoring transplanted liver cells by MRI in a preclinical swine model and used this approach to evaluate different routes for cell application. Liver cells were isolated from landrace piglets and labeled with micron-sized iron oxide particles (MPIO) in adhesion. Labeled cells (n = 10), native cells (n = 3), or pure particles (n = 4) were transplanted to minipigs via intraportal infusion into the liver, direct injection into the splenic parenchyma, or intra-arterial infusion to the spleen. Recipients were investigated by repeated 3.0 Tesla MRI and computed tomography angiography up to 8 weeks after transplantation. Labeling with MPIO, which are known to have a strong effect on the magnetic field, enabled noninvasive detection of cell aggregates by MRI. Following intraportal application, which is commonly applied for clinical LCT, MRI was able to visualize the microembolization of transplanted cells in the liver that were not detected by conventional imaging modalities. Cells directly injected into the spleen were retained, whereas cell infusions intra-arterially into the spleen led to translocation and engraftment of transplanted cells in the liver, with significantly fewer microembolisms compared to intraportal application. These findings demonstrate that MRI can be a valuable tool for noninvasive elucidation of cellular processes of LCT and—if clinically applicable MPIO are available—for monitoring of LCT under clinical conditions. Moreover, the results clarify mechanisms relevant for clinical practice of LCT, suggesting that the intra-arterial route to the spleen deserves further evaluation.

Key words: Liver cell transplantation (LCT); Magnetic resonance imaging (MRI); Cell tracking; Micron-sized iron oxide particles (MPIO); Iron oxide particle

Address correspondence to Nathanael Raschzok, General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel: ++49 30 450 659078; Fax: ++49 30 450 559987; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Igor M. Sauer, M.D., Ph.D., General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel: ++49 30 450 559002; Fax: ++49 30 450 559987; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 137–142, 2010
2155-1790/10 $90.00 + .00
DOI: 10.3727/215517910X552818
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Acute Treatment With Herbal Extracts Provides Neuroprotective Benefits in In Vitro and In Vivo Stroke Models, Characterized by Reduced Ischemic Cell Death and Maintenance of Motor and Neurological Functions

Yuji Kaneko,*1 David J. Eve,*1 SeongJin Yu,* Hideki Shojo,*† Eunkyung Cate Bae,* Dong-Hyuk Park,*‡ Bill Roschek, Jr.,§ Randall S. Alberte,§ Paul R. Sanberg,* Cyndy D. Sanberg,¶ Paula C. Bickford,*# and Cesar V. Borlongan*

*Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, FL, USA
†Department of Legal Medicine, Interdisciplinary Graduate School of Medicine and Engineering University of Yamanashi, Yamanashi, Japan
‡Department of Neurosurgery, Korea University Medical Center, Korea University College of Medicine, Seoul, Korea
§HerbalScience Group LLC, Naples, FL, USA
¶Natura Therapeutics, Inc., Tampa, FL, USA
#James A. Haley Veterans Adminstration Hospital, Tampa FL, USA

The present study explored the prophylactic and restorative benefits of cacao and red sage using both in vitro and in vivo models of stroke. For the in vitro study, we initially exposed primary rat cells to the established oxygen-glucose deprivation (OGD) stroke model followed by reperfusion under normoxic conditions, then added different cacao and sage concentrations to the cell culture media. Trypan blue cell viability results revealed specific cacao and sage dosages exerted significant therapeutic effects against OGD-induced cell death compared to cultured cells treated with extract vehicle. We next embarked on testing the therapeutic effects of cacao and sage in an in vivo model of stroke when extract treatment commenced either prior to or after transient middle cerebral artery occlusion (MCAo). Significant reduction in ischemic cell death within the peri-infarct area coupled with better performance in routine motor and neurological tasks were demonstrated by stroke animals that received cacao or sage extracts prior to MCAo compared to those that received the extracts or vehicle after MCAo. In summary, the present results demonstrate that neuroprotective effects were afforded by plant extract treatment, and that the in vitro stroke paradigm approximates in vivo efficacy when considering prophylactic treatment for stroke.

Key words: Oxygen-glucose deprivation (OGD); Stroke; Prophylactic; Middle cerebral artery occlusion (MCAo); Plant extracts

1These authors provided equal contribution to this work.
Address correspondence to Cesar V. Borlongan, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd., Tampa, FL 33612, USA. Tel: 813-974-3154; Fax: 813-974-3078; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Volume 1, Number 2

Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 71–80, 2010
2155-1790/10 $90.00 + .00
DOI: 10.3727/215517910X536618
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved


Intracerebroventricular Transplantation of Cord Blood-Derived Neural Progenitors in a Child With Severe Global Brain Ischemic Injury

Sergiusz Jozwiak,* Aleksandra Habich,† Katarzyna Kotulska,* Anna Sarnowska,† Tomasz Kropiwnicki,‡ Miroslaw Janowski,† Elzbieta Jurkiewicz,§ Barbara Lukomska,† Tomasz Kmiec,* Jerzy Walecki,¶ Marcin Roszkowski,‡ Mieczyslaw Litwin,# Tomasz Oldak,** Dariusz Boruczkowski,** and Krystyna Domanska-Janik†

*Department of Neurology and Epileptology, The Children’s Memorial Health Institute, Warsaw, Poland
†NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
‡Department of Neurosurgery, The Children’s Memorial Health Institute, Warsaw, Poland
§Department of Radiology, MR Unit, The Children’s Memorial Health Institute, Warsaw, Poland
¶Department of Radiology and Diagnostic Imaging, Postgraduate Medical Centre and Experimental Pharmacology Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
#Department of Nephrology, The Children’s Memorial Health Institute, Warsaw, Poland
**Polish Stem Cell Bank, Warsaw, Poland

Transplantation of neural stem/precursor cells has recently been proposed as a promising, albeit still controversial, approach to brain repair. Human umbilical cord blood could be a source of such therapeutic cells, proven beneficial in several preclinical models of stroke. Intracerebroventricular infusion of neutrally committed cord blood-derived cells allows their broad distribution in the CNS, whereas additional labeling with iron oxide nanoparticles (SPIO) enables to follow the fate of engrafted cells by MRI. A 16-month-old child at 7 months after the onset of cardiac arrest-induced global hypoxic/ischemic brain injury, resulting in a permanent vegetative state, was subjected to intracerebroventricular transplantation of the autologous neutrally committed cord blood cells. These cells obtained by 10-day culture in vitro in neurogenic conditions were tagged with SPIO nanoparticles and grafted monthly by three serial injections (12 × 106 cells/0.5 ml) into lateral ventricle of the brain. Neural conversion of cord blood cells and superparamagnetic labeling efficiency was confirmed by gene expression, immunocytochemistry, and phantom study. MRI examination revealed the discrete hypointense areas appearing immediately after transplantation in the vicinity of lateral ventricles wall with subsequent lowering of the signal during entire period of observation. The child was followed up for 6 months after the last transplantation and his neurological status slightly but significantly improved. No clinically significant adverse events were noted. This report indicates that intracerebroventricular transplantation of autologous, neutrally committed cord blood cells is a feasible, well tolerated, and safe procedure, at least during 6 months of our observation period. Moreover, a cell-related MRI signal persisted at a wall of lateral ventricle for more than 4 months and could be monitored in transplanted brain hemisphere.

Key words: Cord blood; Neural progenitors; Clinical transplantation; Brain ischemia

Address correspondence to Prof. Krystyna Domanska-Janik, NeuroRepair Department, Mossakowski Medical Research Centre, 5 Pawinskiego str, 02-106 Warsaw, Poland. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 81–92, 2010
2155-1790/10 $90.00 + .00
DOI: 10.3727/215517910X536627
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Transplant of Primary Human Hepatocytes Cocultured With Bone Marrow Stromal Cells to SCID Alb-uPA Mice

S. A. Mohajerani,* M. Nourbakhsh,* A. Cadili,* J. R. Lakey,† and N. M. Kneteman*

*Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
†Division of Surgical Research, Department of Surgery, University of California, Irvine, CA, USA

Hepatocytes are vulnerable to loss of function and viability in culture. Modified culture methods have been applied to maintain their functional status. Heterotypic interactions between hepatocytes and nonparenchymal neighbors in liver milieu are thought to modulate cell differentiation .Cocultivation of hepatocyte with various cell types has been applied to mimic the hepatic environment. Bone marrow stromal cells (BMSC) are plastic cell lines capable of transforming to other cell types. In this study hepatocyte coculture with BMSCs achieved long-term function of human hepatocytes in culture for 4 weeks. In vitro functional status of human hepatocytes in BMSC coculture was compared with fibroblast coculture and collagen culture by measuring albumin, human-á-1-antitrypsin (hAAT), urea secretion, CYP450 activity, and staining for intracellular albumin and glycogen. After 2 weeks in culture hepatocytes were retrieved and transplanted to severe combined immunodeficiency/albumin linked-urokinase type plasminogen activator (SCID Alb-uPA) mice and engraftment capacity was analyzed by human hepatic-specific function measured by hAAT levels in mouse serum, and Alu staining of mouse liver for human hepatocytes. Hepatocytes from BMSC coculture had significantly higher albumin, hAAT secretion, urea production, and cytochrome P450 (CYP450) activity than other culture groups. Staining confirmed the higher functional status in BMSC coculture. Transplantation of hepatocytes detached from BMSC cocultures showed significantly higher engraftment function than hepatocytes from other culture groups measured by hAAT levels in mouse serum. In conclusion, BMSC coculture has excellent potential for hepatocyte function preservation in vitro and in vivo after transplant. It is possible to use BMSC hepatocyte coculture as a supply of cell therapy in liver disease.

Key words: Human hepatocytes; Bone marrow stromal cells; In vitro function; SCID-uPA mouse; In vivo function

Address correspondence to Dr. Norman M Kneteman, 2D4 Walter C Mackenzie, University of Alberta Hospital, Edmonton, Alberta, Canada. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 93–103, 2010
2155-1790/10 $90.00 + .00
DOI: 10.3727/215517910X528969
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

In Vivo Growing of New Cell Colonies in a Portion of Bone Marrow: Potential Use for Indirect Cell Therapy

Ana Manzanedo,* Fidel Rodriguez,† Jose A. Obeso,‡§ and Manuel Rodriguez*§

*Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain
†Department of Pharmacology and Physical Medicine, Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain
‡Department of Neurology and Neurosurgery, Clinica Universitaria and Medical School, Centro de Investigación Médica Aplicada (CIMA), University of Navarra, Pamplona, Spain
§Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

The ability of bone marrow cells (BMCs) to migrate to different organs can be used for indirect cell therapy, a procedure based on the engraftment of therapeutic cells in a different place from where they will finally move to and perform their action and which could be particularly useful for chronic illness where a persistent and long-lasting therapeutic action is required. Thus, establishing a stable colony of engineered BMCs is a requisite for the chronic provision of damaged tissues with engineered cells. Reported here is a procedure for creating such a cell colony in a portion of the bone marrow (BM). The study was performed in C57BL/6j mice and consisted of developing a focal niche in a portion of the bone marrow with focal irradiation so that it could be selectively colonized by BM cells (C57BL/6-FG-VC-GFP mice) injected in the blood stream. Both the arrival of cells coming from the nonirradiated BM (week 1 after irradiation) and the proliferation of cells in the irradiated BM (week 2) prevented the homing of injected cells in the BM niche. However, when BMCs were injected in a time window about 48 h after irradiation they migrated to the BM niche where they established a cell colony able to: 1) survive for a long period of time [the percentage of injected cells increased in the BM from day 30 postinjection (15%) to day 110 postinjection 28%)]; 2) express cell differentiation markers (90% of them were lineage committed 4 weeks after engraftment); and 3) colonize to the blood stream (with 5% and 9% of all blood cells being computed 1 and 3 months after engraftment, respectively). The intravenous injection of BMCs in combination with a previous transitory focal myeloablation is a safe and easy method for creating the long-lasting colony of modified BMCs needed for treating chronic and progressive illness with indirect cell therapy.

Key words: Bone marrow; Stem cells; Myeloablation; Cell transplantation; Parkinson’s disease; GFP

Address correspondence to Manuel Rodriguez, Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain. Fax: 34-922-319397; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 105–112, 2010
2155-1790/10 $90.00 + .00
DOI: 10.3727/215517910X451603
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved


Effects of Quantum Dot Labeling on Endothelial Progenitor Cell Function and Viability

Matyas Molnar,*† Peter Friberg,* Ying Fu,† Mikeal Brisslert,‡ Michael Adams,§ and Yun Chen*†

*Department of Molecular and Clinical Medicine/Clinical Physiology, The Sahlgrenska Academy and University Hospital, University of Gothenburg, Gothenburg, Sweden
†Department of Theoretical Chemistry, School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden
‡Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy and University Hospital, University of Gothenburg, Gothenburg, Sweden
§Department of Pharmacology and Toxicology, Queen’s University, Kingston, Ontario, Canada

Endothelial progenitor cells (EPC) play an important role in repairing damaged endothelium. An effective imaging method for in vivo tracking of EPCs is essential for understanding EPC-based cell therapy. Fluorescent quantum dots (QDs) have attractive optical characteristics such as extreme brightness and photostability. QDs are currently being investigated as probes for stem cell labeling; however, there is concern about whether QDs can be used safely. We investigated whether quantum dot (QD) labeling would influence EPC viability and function. Rat bone marrow-derived EPCs were cultured and characterized. The cells were labeled with near-infrared-emitting, carboxyl-coated QDs (8 nM) for 24 h. QD labeling efficiency was higher than 97%. Using WST-1 assay, we showed that the viability of the QD-labeled EPCs was not different from that of the control EPCs. Moreover, QD labeling did not influence the ability of EPCs to form capillary tubes on Matrigel and to migrate. The percentage of QD-positive cells decreased with time, probably due to the rapid division of EPCs. These data suggest that the carboxyl-coated QD705 can be useful for labeling EPCs without interrupting their viability and functions.

Key words: Endothelial progenitor cells; Quantum dots; Cell labeling; Migration; Capillary tube formation

Address correspondence to Yun Chen, Associate Professor, Wallenberg Laboratory, Bruna Stråket 16, The Sahlgrenska Academy and University Hospital, University of Gothenburg, SE 413 45 Gothenburg, Sweden. Tel: 46-31-3428407; Fax: 46-31-823762; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it