Cell Medicine (5)1 Abstracts

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Cell Medicine, Vol. 5, pp. 1–16, 2013
2155-1790/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517913X666459
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Human Liver Progenitor Cells for Liver Repair

Catherine A. Lombard, Julie Prigent, and Etienne M. Sokal

Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, Pediatric Hepatology and Cell Therapy, Brussels, Belgium

Because of their high proliferative capacity, resistance to cryopreservation, and ability to differentiate into hepatocyte-like cells, stem and progenitor cells have recently emerged as attractive cell sources for liver cell therapy, a technique used as an alternative to orthotopic liver transplantation in the treatment of various hepatic ailments ranging from metabolic disorders to end-stage liver disease. Although stem and progenitor cells have been isolated from various tissues, obtaining them from the liver could be an advantage for the treatment of hepatic disorders. However, the techniques available to isolate these stem/progenitor cells are numerous and give rise to cell populations with different morphological and functional characteristics. In addition, there is currently no established consensus on the tests that need to be performed to ensure the quality and safety of these cells when used clinically. The purpose of this review is to describe the different types of liver stem/progenitor cells currently reported in the literature, discuss their suitability and limitations in terms of clinical applications, and examine how the culture and transplantation techniques can potentially be improved to achieve a better clinical outcome.

Key words: Stem/progenitor cells; Cell therapy; Metabolic disorders; Liver; Regenerative medicine

Received June 4, 2012; final acceptance March 20, 2013. Online prepub date: April 29, 2013.
Address correspondence to Professor Etienne M. Sokal, M.D., Ph.D., Cliniques Universitaires Saint-Luc, Paediatric Gastroenterology and Hepatology Unit, Avenue Hippocrate 10, B-1200 Brussels, Belgium. Tel: +32-2-7641387; Fax: +32-2-7648909; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 5, pp. 17–28, 2013
2155-1790/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517913X658936
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Transplantation of Human Adipose Tissue-Derived Mesenchymal Stem Cells Restores the Neurobehavioral Disorders of Rats With Neonatal Hypoxic-Ischemic Encephalopathy

Dongsun Park,*1 Sun Hee Lee,*1 Dae Kwon Bae,* Yun-Hui Yang,* Goeun Yang,* Jangbeen Kyung,* Dajeong Kim,* Ehn-Kyoung Choi,* Jin Tae Hong,† Il Seob Shin,‡ Sung Keun Kang,‡ Jeong Chan Ra,‡ and Yun-Bae Kim*

*College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
†College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea
‡Stem Cell Research Center, RNL BIO Co., Ltd., Seoul, Republic of Korea

Improving the effects of human adipose tissue-derived mesenchymal stem cells (ASCs) on the demyelination and neurobehavioral function was investigated in an experimental model of neonatal hypoxic-ischemic encephalopathy (HIE). Seven-day-old male rats were subjected to hypoxia-ischemia-lipopolysaccharide and intracerebroventricularly transplanted with human ASCs (4 × 105 cells/rat) once at postnatal day 10 (PND10) or repeatedly at PND10, 17, 27, and 37. Neurobehavioral abnormalities (at PND20, 30, and 40) and cognitive functions (at PND41–44) were evaluated using multiple test systems. Human ASCs recovered the using ratio of forelimb contralateral to the injured brain, improved locomotor activity, and restored rota-rod performance of HIE animals, in addition to showing a marked improvement of cognitive functions. It was confirmed that transplanted human ASCs migrated to injured areas and differentiated into oligodendrocytes expressing myelin basic protein (MBP). Moreover, transplanted ASCs restored production of growth and neurotrophic factors and expression of decreased inflammatory cytokines, leading to attenuation of host MBP loss. The results indicate that transplanted ASCs restored neurobehavioral functions by producing MBP as well as by preserving host myelins, which might be mediated by ASCs’ anti-inflammatory activity and release of growth and neurotrophic factors.

Key words: Neonatal hypoxic-ischemic encephalopathy (HIE); Adipose tissue-derived mesenchymal stem cell (ASC); Differentiation; Neurobehavior; Cognition; Anti-inflammation; Growth/neurotrophic factor

Received July 26, 2012; final acceptance January 28, 2013. Online prepub date: February 7, 2013.
1These authors provided equal contribution to this work.
Address correspondence to Dr. Yun-Bae Kim, College of Veterinary Medicine, Chungbuk National University, 52 Naesudongro (Gaesin-dong), Cheongju, Chungbuk 361-763, Republic of Korea. Tel: +82-43-261-3358; Fax: +82-43-271-3246; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Dr. Jeong Chan Ra, Stem Cell Research Center, RNL Bio Co., Ltd., 2-305 IT Castle Gasan-dong, Geumcheon-gu, Seoul 153-768, Republic of Korea. Tel: +82-2-858-8021; Fax: +82-2-858-8140; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 5, pp. 29–42, 2013
2155-1790/13 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517913X666468
Copyright © 2013 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Phenotype and Stability of Neural Differentiation of Androgenetic Murine ES Cell-Derived Neural Progenitor Cells

Wanja Wolber,*1 Ruhel Ahmad,†1 Soon Won Choi,†1,2 Sigrid Eckardt,‡ K. John McLaughlin,‡ Jessica Schmitt,† Christian Geis,§ Manfred Heckmann,¶ Anna-Leena Siren,* and Albrecht M. Muller†

*Department of Neurosurgery, University of Wurzburg, Wurzburg, Germany
†Institute for Medical Radiation and Cell Research (MSZ) in the Center of Experimental and Molecular Medicine (ZEMM), University of Wurzburg, Wurzburg, Germany
‡Nationwide Children’s Research Institute, Columbus, OH, USA
§Department of Neurology, University of Wurzburg, Wurzburg, Germany
¶Institute for Physiology, University of Wurzburg, Wurzburg, Germany

Uniparental zygotes with two paternal (androgenetic, AG) or two maternal genomes (gynogenetic, GG) cannot develop into viable offsprings but form blastocysts from which pluripotent embryonic stem (ES) cells can be derived. For most organs, it is unclear whether uniparental ES cells can give rise to stably expandable somatic stem cells that can repair injured tissues. Even if previous reports indicated that the capacity of AG ES cells to differentiate in vitro into pan-neural progenitor cells (pNPCs) and into cells expressing neural markers is similar to biparental [normal fertilized (N)] ES cells, their potential for functional neurogenesis is not known. Here we show that murine AG pNPCs give rise to neuron-like cells, which then generate sodium-driven action potentials while maintaining fidelity of imprinted gene expression. Neural engraftment after intracerebral transplantation was achieved only by late (22 days) AG and N pNPCs with in vitro low colony-forming cell (CFC) capacity. However, persisting CFC formation seen, in particular, in early (13 or 16 days) differentiation cultures of N and AG pNPCs correlated with a high incidence of trigerm layer teratomas. As AG ES cells display functional neurogenesis and in vivo stability similar to N ES cells, they represent a unique model system to study the roles of paternal and maternal genomes on neural development and on the development of imprinting-associated brain diseases.

Key words: Embryonic stem (ES) cell; Uniparental; Electrophysiology; Teratoma; Brain injury

Received June 29, 2012; final acceptance May 29, 2013. Online prepub date: June 13, 2013.
1The authors provided equal contribution to this work.
2Present address: Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Republic of Korea.
Address correspondence to Albrecht M. Muller, Institute for Medical Radiation and Cell Research (MSZ) in the Center of Experimental and Molecular Medicine (ZEMM), University of Wurzburg, Zinklesweg 10, 97078 Wurzburg, Germany. Tel: +(49) 931-201 45848; Fax: +(49) 931-201 45147; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Anna-Leena Siren, Department of Neurosurgery, University of Wurzburg, Josef-Schneider Str. 11, 97080 Wurzburg, Germany. Tel: +(49) 931-201 24579; Fax: +(49) 931-201 24140; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it