Labelling and Tracking of Human Mesenchymal Stromal Cells in Preclinical Studies and Large Animal Models of Degenerative Diseases

Author(s):

Martin Vaegler, Jan K. Maerz, Bastian Amend, Luis Arenas da Silva, Julia G. Mannheim, Kerstin Fuchs, Susanne Will, Karl D. Sievert, Arnulf Stenzl, Melanie L. Hart and Wilhelm K. AicherPages 444-450 (7)

Abstract:

Success of stem cell therapies were reported in different medical disciplines, including haematology, rheumatology, orthopaedic surgery, traumatology, and others. Currently, more than 4000 clinical trials using stem cells have been completed or are underway, among which 378 investigated or are at present investigating mesenchymal stromal cells (MSCs). The majority of clinical trials using stem- or progenitor- cells, including hematopoietic stem cells and MSCs, target the immune system. However, therapies based on MSCs are increasingly implemented to treat symptoms in which failure of the resident stem cells in situ, or malfunction of tissues or structures are not associated with immune cells or inflammation, but instead are associated with mechanical or metabolic stress, ageing, developmental or acquired malformations, and other causes. To proceed further in the development of stem cell therapies as a safe and effective treatment for surgical and other medical specialities, the behaviour of MSCs implanted in preclinical models and their impact on the site of application need to be explored in detail. Depending on the pre-clinical model employed, tracking of labelled stem cells in live animals makes an enormous difference for exploration of the mechanisms and kinetics involved in MSC-mediated tissue regeneration. Here we review (pre-)clinically applicable key methods to label human MSCs for short and long-term observations in small and large animal models.

Keywords:

Cell labelling, magnet resonance imaging (MRI), mesenchymal stromal cell / mesenchymal stem cell (MSC), positron emission tomography (PET).

Affiliation:

KFO273, Department of Urology, UKT, University of Tuebingen, Paul-Ehrlich-Str. 15, 72076 Tuebingen, Germany.

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Beta Cell Regeneration in Adult Mice: Controversy over the Involvement of Stem Cells

Author(s):

Ke Yu, Shane Fischbach and Xiangwei XiaoPages 1-5 (5)

Abstract:

Islet transplantation is an effective therapy for severe diabetes. Nevertheless, the short supply of donor pancreases constitutes a formidable obstacle to its extensive clinical application. This shortage heightens the need for alternative sources of insulin-producing beta cells. Since mature beta cells have a very slow proliferation rate, which further declines with age, great efforts have been made to identify beta cell progenitors in the adult pancreas. However, the question whether facultative beta cell progenitors indeed exists in the adult pancreas remains largely unresolved. In the current review, we discuss the problems in past studies and review the milestone studies and recent publications

Keywords:

Beta cell mass, beta cell neogenesis, beta cell regeneration, Ngn3

Affiliation:

Division of Pediatric Surgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 4401 Penn Ave, Pittsburgh, PA 15224, USA

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Non-Viral Methods For Generating Integration-Free, Induced Pluripotent Stem Cells

Author(s):

Xiao-Yue Deng, Hu Wang, Tao Wang, Xian-Tao Fang, Li-Li Zou, Zhi-Ying Li and Chang-Bai LiuPages 153-158 (6)

Abstract:

Induced pluripotent stem (iPS) cells were created from mouse fibroblasts by induced expression of Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc. This technique has quickly resulted in an exponential increase in the amount of pluripotency studies, and has provided a valuable tool in regenerative medicine. At the same time, many methodologies to generate iPS cells have been reported, and are comprised mainly of viral methods and non-viral methods. Although viral methods may not be applicable for clinical applications, various nonviral methods have been reported in recent years, including DNA vector-based approaches, transfection of mRNA, transduction of reprogramming proteins, and use of small molecule compounds. This review summarizes and evaluates these non-viral methods.

Keywords:

DNA integration-free, induced pluripotent stem cells, non-viral methods.

Affiliation:

Institute of Molecular Biology, China Three Gorges University, 8 Daxuelu, Yichang, China.

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Hospital Exemption for Advanced Therapy Medicinal Products: Issue in Application in the European Union Member States

Author(s):

Tatjana Ivaskiene, Mykolas Mauricas and Justinas IvaskaPages 1-7 (7)

Abstract:

Regulation (EC) 1394/2007 of the European Parliament and the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 allowed the use of non - authorized advanced therapy medicinal products under the certain circumstances. This socalled hospital exemption rule needs to be applied in the each Member State of the European Union individually and for this purpose Member States should provide national procedures and control measures. The aim of this article is to clear up the criteria for hospital exemption listed in Regulation (EC) 1394/2007 and to contrast the difference in implementing hospital exemption rule into national legal regimes on examples of the United Kingdom, Lithuania and Poland.

Keywords:

Advanced therapy medicinal product, hospital exemption, regulation.

Affiliation:

Vilnius University, Centre of Otorhinolaryngology, Universiteto st. 3, LT-01513, Vilnius, Lithuania.

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Research Advancements in Porcine Derived Mesenchymal Stem Cells

Author(s):

Dinesh Bharti, Sharath Belame Shivakumar, Raghavendra Baregundi Subbarao and Gyu-Jin RhoPages 78-93 (16)

Abstract:

In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs) before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical issues, successful MSC isolation from different origins like bone marrow, skin, umbilical cord blood, Wharton’s jelly, endometrium, amniotic fluid and peripheral blood make porcine a good model for stem cell therapy. Porcine derived MSCs (pMSCs) have shown greater in vitro differentiation and transdifferention potential towards mesenchymal lineages and specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous and heterologous MSCs proves them safe and appropriate models for xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs can be of immense importance in relation to various osteochondral defects which are difficult to treat otherwise. Using pMSCs successful treatment of various disorders like Parkinson’s disease, cardiac ischemia, hepatic failure, has been reported by many studies. Here, in this review we highlight current research findings in the area of porcine mesenchymal stem cells dealing with their isolation methods, differentiation ability, transplantation applications and their therapeutic potential towards various diseases.

Keywords:

Cell therapy, mesenchymal stem cells, multipotency, porcine.

Affiliation:

OBS/Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 900 Gazwa, Jinju 660-701, Republic of Korea.

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