ognizant Communication Corporation

Part B of Cell Transplantation

VOLUME 1, NUMBER 1, 2010

Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 15-46, 2010
2155-1790/10 $90.00 + 00
DOI: 10.3727/215517910X516673
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Cell Therapy From Bench to Bedside Translation in CNS Neurorestoratology Era

Hongyun Huang,1 Lin Chen,1 and Paul Sanberg2

1Center for Neurorestoratology, Beijing Rehabilitation Center, Beijing, P.R. China
2Department of Neurosurgery, University of South Florida, Tampa, FL, USA

Recent advances in cell biology, neural injury and repair, and the progress towards development of neurorestorative interventions are the basis for increased optimism. Based on the complexity of the processes of demyelination and remyelination, degeneration and regeneration, damage and repair, functional loss and recovery, it would be expected that effective therapeutic approaches will require a combination of strategies encompassing neuroplasticity, immunomodulation, neuroprotection, neurorepair, neuroreplacement, and neuromodulation. Cell-based restorative treatment has become a new trend, and increasing data worldwide have strongly proven that it has a pivotal therapeutic value in CNS disease. Moreover, functional neurorestoration has been achieved to a certain extent in the CNS clinically. Up to now, the cells successfully used in preclinical experiments and/or clinical trial/treatment include fetal/embryonic brain and spinal cord tissue, stem cells (embryonic stem cells, neural stem/progenitor cells, hematopoietic stem cells, adipose-derived adult stem/precursor cells, skin-derived precursor, induced pluripotent stem cells), glial cells (Schwann cells, oligodendrocyte, olfactory ensheathing cells, astrocytes, microglia, tanycytes), neuronal cells (various phenotypic neurons and Purkinje cells), mesenchymal stromal cells originating from bone marrow, umbilical cord, and umbilical cord blood, epithelial cells derived from the layer of retina and amnion, menstrual blood-derived stem cells, Sertoli cells, and active macrophages, etc. Proof-of-concept indicates that we have now entered a new era in neurorestoratology.

Key words: Cell therapy; Translational medicine; Neurorestoratology; Central nervous system diseases

Address correspondence to Hongyun Huang, Center for neurorestoratology, Beijing Rehabilitation Center, Beijing, 100144, P.R. China. Tel: 86-10-5882-3400; Fax: 86-10-5162-5950; E-mail: hongyunh@gmail.com

Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 47-54, 2010
2155-1790/10 $90.00 + 00
DOI: 10.3727/215517910X516646
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

New Strategies for Acute Liver Failure: Focus on Xenotransplantation Therapy

Luiz Anastácio Alves,1 André Bonavita,1 Kátia Quaresma,1 Elenilde Torres,1 Paulo Anastácio Furtado Pacheco,1 Vinícius Cotta-de-Almeida,2 and Roberto Magalhães Saraiva3

1Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
2Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
3Instituto de Pesquisa Evandro Chagas (IPEC), Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

Acute liver failure (ALF) has a poor prognosis and, despite intensive care support, reported average survival is only 10-40%. The most common causes responsible for ALF are viral hepatitis (mainly hepatitis A and B) and acetaminophen poisoning. Hepatic transplantation is the only appropriate treatment for patients with unlikely survival with supportive care alone. Survival rates after transplantation can be as high as 80-90% at the end of the first year. However, there is a shortage of donors and is not uncommon that no appropriate donor matches with the patient in time to avoid death. Therefore, new technologies are in constant development, including blood purification therapies as plasmapheresis, hemodiafiltration, and bioartificial liver support. However, they are still of limited efficacy or at an experimental level, and new strategies are welcome. Accordingly, cell transplantation has been developed to serve as a possible bridge to spontaneous recovery or liver transplantation. Xenotransplant of adult hepatocytes offers an interesting alternative. Moreover, the development of transgenic pigs with less immunogenic cells associated with new immunosuppressor strategies has allowed the development of this area. This article reviews some of the newly developed techniques, with focus on xenotransplant of adult hepatocytes, which might have clinical benefits as future treatment for ALF.

Key words: Xenotransplantation; Acute liver failure; Cell therapy; Survival

Address correspondence to Luiz Anastácio Alves, M.D., Ph.D., Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz-FIOCRUZ, Av. Brasil, 4365 Manguinhos, Rio de Janeiro, Brazil, 21045-900. E-mail: alveslaa@ioc.fiocruz.br

Cell Medicine, Part B of Cell Transplantation, Vol. 1, pp. 55-70, 2010
2155-1790/10 $90.00 + 00
DOI: 10.3727/215517910X519274
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.

Liver Cell Culture Devices

B. Andria,1,2 A. Bracco,1 G. Cirino,2 and R. A. F. M. Chamuleau3

1Center of Biotechnologies, Cardarelli Hospital, Naples, Italy
2Faculty of Pharmacy, "Federico II" University, Naples, Italy
3Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, Amsterdam, The Netherlands

In the last 15 years many different liver cell culture devices, consisting of functional liver cells and artificial materials, have been developed. They have been devised for numerous different applications, such as temporary organ replacement (a bridge to liver transplantation or native liver regeneration) and as in vitro screening systems in the early stages of the drug development process, like assessing hepatotoxicity, hepatic drug metabolism, and induction/inhibition studies. Relevant literature is summarized about artificial human liver cell culture systems by scrutinizing PubMed from 2003 to 2009. Existing devices are divided in 2D configurations (e.g., static monolayer, sandwich, perfused cells, and flat plate) and 3D configurations (e.g., liver slices, spheroids, and different types of bioreactors). The essential features of an ideal liver cell culture system are discussed: different types of scaffolds, oxygenation systems, extracellular matrixes (natural and artificial), cocultures with nonparenchymal cells, and the role of shear stress problems. Finally, miniaturization and high-throughput systems are discussed. All these factors contribute in their own way to the viability and functionality of liver cells in culture. Depending on the aim for which they are designed, several good systems are available for predicting hepatotoxicity and hepatic metabolism within the general population. To predict hepatotoxicity in individual cases genomic analysis might be essential as well.

Key words: Cell culture devices; Human liver cells; Drug delivery; Bioreactor

Address correspondence to R. A. F. M. Chamuleau, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Meibergdreef 69-71, S. Building , Floor 1, Room 166, 1105 BK, Amsterdam, The Netherlands. Tel: +31-20-5668832; Fax: +31-20-5669190; E-mail: r.a.chamuleau@amc.uva.nl