http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Wed, 19 Jun 2013 18:17:12 +0000 http://www.hindawi.com/journals/sci/2013/353097/ Myocarditis is a common inflammatory cardiomyopathy, associated with cardiomyocyte apoptosis, which can lead to chronic left ventricular dysfunction. Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. Experimental and clinical studies consistently support the application of cellular transplantation as a strategy to improve myocardial function. Mesenchymal stromal cells (MSCs) mediate distinct paracrine effects supporting endogenous regeneration, but most important are their remarkable immunoregulatory properties. In this review, an overview of current knowledge on immunopathology in myocarditis will be given. Furthermore, current research regarding the immunomodulatory properties of MSCs in the context of myocarditis will be discussed. Finally, the impact of MSC priming by the environment on their functionality and the advantages of systemic administration of MSCs under myocarditis are outlined. Kapka Miteva, Sophie Van Linthout, Hans-Dieter Volk, and Carsten Tschöpe Copyright © 2013 Kapka Miteva et al. All rights reserved. Wed, 19 Jun 2013 15:41:30 +0000 http://www.hindawi.com/journals/sci/2013/178346/ Regenerative therapies hold a promising and exciting future for the cure of yet untreatable diseases, and mesenchymal stem cells are in the forefront of this approach. However, the relative efficacy and the mechanism of action of different types of mesenchymal stem cells are still incompletely understood. We aimed to evaluate the effects of human adipose- (hASC) and bone-marrow-derived stem cells (hBMSCs) and adipose-derived stem cell conditioned media (ACM) on the viability of cardiomyoblasts in an in vitro ischemia-reperfusion (I-R) model. Flow cytometric viability analysis revealed that both cell treatments led to similarly increased percentages of living cells, while treatment with ACM did not (I-R model: %; hASC: %; hBMSC: %; ACM: %). Metabolic activity measurement (I-R model: ; hASC: ; hBMSC: ; ACM: ; arbitrary units) and lactate dehydrogenase assay (I-R model: ; hASC: ; hBMSC: ; ACM: ; arbitrary units) confirmed the flow cytometric results while also indicated a slight beneficial effect of ACM. Our results highlight that mesenchymal stem cells have the same efficacy when used directly on postischemic cells, and differences found between them in preclinical and clinical investigations are rather related to other possible causes such as their immunomodulatory or angiogenic properties. Mónika Szepes, Zsolt Benkő, Attila Cselenyák, Kai Michael Kompisch, Udo Schumacher, Zsombor Lacza, and Levente Kiss Copyright © 2013 Mónika Szepes et al. All rights reserved. Tue, 18 Jun 2013 17:42:49 +0000 http://www.hindawi.com/journals/sci/2013/892065/ Human adult mesenchymal stem cells (MSC) can be readily harvested from bone marrow through aspiration. MSC are involved in tissue regeneration and repair, particularly in wound healing. Due to their high self-renewal capacity and excellent differentiation potential in vitro, MSC are ideally suited for regenerative medicine. The complex interactions of MSC with their environment and their influence on the molecular and functional levels are widely studied but not completely understood. MSC secrete, for example, hepatocyte growth factor (HGF), whose concentration is enhanced in wounded areas and which is shown to act as a chemoattractant for MSC. We produced HGF-loaded biomaterials based on collagen and fibrin gels to develop a recruitment system for endogenous MSC to improve wound healing. Here, we report that HGF incorporated into collagen or fibrin gels leads to enhanced and directed MSC migration in vitro. HGF-loaded biomaterials might be potentially used as in vivo wound dressings to recruit endogenous MSC from tissue-specific niches towards the wounded area. This novel approach may help to reduce costly multistep procedures of cell isolation, in vitro culture, and transplantation usually used in tissue engineering. Julia van de Kamp, Willi Jahnen-Dechent, Bjoern Rath, Ruth Knuechel, and Sabine Neuss Copyright © 2013 Julia van de Kamp et al. All rights reserved. Thu, 06 Jun 2013 12:27:11 +0000 http://www.hindawi.com/journals/sci/2013/137010/ Mesenchymal stem cells (MSCs) can differentiate into osteoblasts and lead to bone formation in the body. Osteoblast differentiation and bone development are regulated by a network of molecular signals and transcription factors induced by several proteins, including BMP2, osterix, and Runx2. We recently observed that the growth-arrest-specific 7 gene (Gas7) is upregulated during differentiation of human MSCs into osteoblasts. Downregulation of Gas7 using short-hairpin RNA decreased the expression of Runx2, a master regulator of osteogenesis, and its target genes (alkaline phosphatase, type I collagen, osteocalcin, and osteopontin). In addition, knockdown of Gas7 decreased the mineralization of dexamethasone-treated MSCs in culture. Conversely, ectopic expression of Gas7 induced Runx2-dependent transcriptional activity and gene expression leading to osteoblast differentiation and matrix mineralization. Genetic mutations of the Gas7 gene increased body fat levels and decreased bone density in mice. These results showed that Gas7 plays a role in regulating the pathways which are essential for osteoblast differentiation and bone development. In this review, we summarize the involvement of Gas7 in MSC-based osteogenesis and osteoporosis and describe the possible mechanisms responsible for the maintenance of cellular homeostasis in MSCs and osteoblasts. Chuck C.-K. Chao, Feng-Chun Hung, and Jack J. Chao Copyright © 2013 Chuck C.-K. Chao et al. All rights reserved. Sun, 02 Jun 2013 18:33:25 +0000 http://www.hindawi.com/journals/sci/2013/420164/ Adult stem cells play an essential role in mammalian organ maintenance and repair throughout adulthood since they ensure that organs retain their ability to regenerate. The choice of cell fate by adult stem cells for cellular proliferation, self-renewal, and differentiation into multiple lineages is critically important for the homeostasis and biological function of individual organs. Responses of stem cells to stress, injury, or environmental change are precisely regulated by intercellular and intracellular signaling networks, and these molecular events cooperatively define the ability of stem cell throughout life. Skeletal muscle tissue represents an abundant, accessible, and replenishable source of adult stem cells. Skeletal muscle contains myogenic satellite cells and muscle-derived stem cells that retain multipotent differentiation abilities. These stem cell populations have the capacity for long-term proliferation and high self-renewal. The molecular mechanisms associated with deficits in skeletal muscle and stem cell function have been extensively studied. Muscle-derived stem cells are an obvious, readily available cell resource that offers promise for cell-based therapy and various applications in the field of tissue engineering. This review describes the strategies commonly used to identify and functionally characterize adult stem cells, focusing especially on satellite cells, and discusses their potential applications. Shin Fujimaki, Masanao Machida, Ryo Hidaka, Makoto Asashima, Tohru Takemasa, and Tomoko Kuwabara Copyright © 2013 Shin Fujimaki et al. All rights reserved. Thu, 30 May 2013 15:47:31 +0000 http://www.hindawi.com/journals/sci/2013/762196/ The shortage of donor livers and hepatocytes is a major limitation of liver transplantation. Thus, generation of hepatocyte-like cells may provide alternative choice for therapeutic applications. In this study, we developed a new method to establish hepatocytes from Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) cell lines named WJMSCs-SUT1 and WJMSCs-SUT2 under hypoxic condition. This new method could rapidly drive both WJ-MSCs cell lines into hepatic lineage within 18 days. The achievement of hepatogenic differentiation was confirmed by the characterization of both phenotypes and functions. More than 80% MSCs-derived hepatocyte-like cells (MSCDHCs) achieved functional hepatocytes including hepatic marker expressions both at gene and protein levels, glycogen storage, low-density lipoprotein uptake, urea production, and albumin secretion. This study highlights the establishment of new hepatogenic induction protocol under hypoxic condition in order to mimic hypoxic microenvironment in typical cell physiology. In conclusion, we present a simple, high-efficiency, and time saving protocol for the generation of functional hepatocyte-like cells from WJ-MSCs in hypoxic condition. The achievement of this method may overcome the limitation of donor hepatocytes and provides a new avenue for therapeutic value in cell-based therapy for life-threatening liver diseases, regenerative medicine, toxicity testing for pharmacological drug screening, and other medical related applications. Patcharee Prasajak and Wilairat Leeanansaksiri Copyright © 2013 Patcharee Prasajak and Wilairat Leeanansaksiri. All rights reserved. Thu, 23 May 2013 14:36:29 +0000 http://www.hindawi.com/journals/sci/2013/312501/ Human mesenchymal stem cells (hMSCs) are pluripotent adult stem cells capable of being differentiated into osteoblasts, adipocytes, and chondrocytes. The osteogenic differentiation of hMSCs is regulated either by systemic hormones or by local growth factors able to induce specific intracellular signal pathways that modify the expression and activity of several transcription factors. Runt-related transcription factor 2 (Runx2) and Wnt signaling-related molecules are the major factors critically involved in the osteogenic differentiation process by hMSCs, and SRY-related high-mobility-group (HMG) box transcription factor 9 (SOX9) is involved in the chondrogenic one. hMSCs have generated a great interest in the field of regenerative medicine, particularly in bone regeneration. In this paper, we focused our attention on the molecular mechanisms involved in osteogenic and chondrogenic differentiation of hMSC, and the potential clinical use of hMSCs in osteoarticular pediatric disease characterized by fracture nonunion and pseudarthrosis. Nicola Giuliani, Gina Lisignoli, Marina Magnani, Costantina Racano, Marina Bolzoni, Benedetta Dalla Palma, Angelica Spolzino, Cristina Manferdini, Caterina Abati, Denise Toscani, Andrea Facchini, and Franco Aversa Copyright © 2013 Nicola Giuliani et al. All rights reserved. Wed, 22 May 2013 13:17:05 +0000 http://www.hindawi.com/journals/sci/2013/361637/ Stem cells continue to receive widespread attention due to their potential to revolutionise treatments in the fields of both tissue engineering and regenerative medicine. Adult stem cells, specifically mesenchymal stromal cells (MSCs), play a vital role in the natural events surrounding bone healing and osseointegration through being stimulated to differentiate along their osteogenic lineage and in doing so, they form new cortical and trabecular bone tissue. Understanding how to control, manipulate, and enhance the intrinsic healing events modulated through osteogenic differentiation of MSCs by the use of modified surfaces and biomaterials could potentially advance the fields of both orthopaedics and dentistry. This could be by either using surface modification to generate greater implant stability and more rapid healing following implantation or the stimulation of MSCs ex vivo for reimplantation. This review aims to gather publications targeted at promoting, enhancing, and controlling the osteogenic differentiation of MSCs through biomaterials, nanotopographies, and modified surfaces for use in implant procedures. Niall Logan and Peter Brett Copyright © 2013 Niall Logan and Peter Brett. All rights reserved. Mon, 20 May 2013 14:49:47 +0000 http://www.hindawi.com/journals/sci/2013/507301/ Mesenchymal stem cells (MSCs) are currently defined as multipotent stromal cells that undergo sustained in vitro growth and can give rise to cells of multiple mesenchymal lineages, such as adipocytes, chondrocytes, and osteoblasts. The regenerative and immunosuppressive properties of MSCs have led to numerous clinical trials exploring their utility for the treatment of a variety of diseases (e.g., acute graft-versus-host disease, Crohn’s disease, multiple sclerosis, osteoarthritis, and cardiovascular diseases including heart failure and myocardial infarction). On the other hand, conventionally cultured MSCs reflect heterogeneous populations that often contain contaminating cells due to the significant variability in isolation methods and the lack of specific MSC markers. This review article focuses on recent developments in the MSC research field, with a special emphasis on the identification of novel surface markers for the in vivo localization and prospective isolation of murine and human MSCs. Furthermore, we discuss the physiological importance of MSC subtypes in vivo with specific reference to data supporting their contribution to HSC niche homeostasis. The isolation of MSCs using selective markers (combination of PDGFRα and Sca-1) is crucial to address the many unanswered questions pertaining to these cells and has the potential to enhance their therapeutic potential enormously. Yo Mabuchi, Diarmaid D. Houlihan, Chihiro Akazawa, Hideyuki Okano, and Yumi Matsuzaki Copyright © 2013 Yo Mabuchi et al. All rights reserved. Thu, 16 May 2013 14:30:27 +0000 http://www.hindawi.com/journals/sci/2013/238635/ Stefan Liebau, Alexander Kleger, Michael Levin, and Shan Ping Yu Copyright © 2013 Stefan Liebau et al. All rights reserved. Sun, 12 May 2013 14:04:25 +0000 http://www.hindawi.com/journals/sci/2013/496501/ The generation of induced pluripotent stem cells (iPS cells) has pioneered the field of regenerative medicine and developmental biology. They can be generated by overexpression of a defined set of transcription factors in somatic cells derived from easily accessible tissues such as skin or plucked hair or even human urine. In case of applying this tool to patients who are classified into a disease group, it enables the generation of a disease- and patient-specific research platform. iPS cells have proven a significant tool to elucidate pathophysiological mechanisms in various diseases such as diabetes, blood disorders, defined neurological disorders, and genetic liver disease. One of the first successfully modelled human diseases was long QT syndrome, an inherited cardiac channelopathy which causes potentially fatal cardiac arrhythmia. This review summarizes the efforts of reprogramming various types of long QT syndrome and discusses the potential underlying mechanisms and their application. Martin Müller, Thomas Seufferlein, Anett Illing, and Jörg Homann Copyright © 2013 Martin Müller et al. All rights reserved. Sun, 12 May 2013 08:32:24 +0000 http://www.hindawi.com/journals/sci/2013/916837/ Cardiospheres (CSs) are self-assembling multicellular clusters from the cellular outgrowth from cardiac explants cultured in nonadhesive substrates. They contain a core of primitive, proliferating cells, and an outer layer of mesenchymal/stromal cells and differentiating cells that express cardiomyocyte proteins and connexin 43. Because CSs contain both primitive cells and committed progenitors for the three major cell types present in the heart, that is, cardiomyocytes, endothelial cells, and smooth muscle cells, and because they are derived from percutaneous endomyocardial biopsies, they represent an attractive cell source for cardiac regeneration. In preclinical studies, CS-derived cells (CDCs) delivered to infarcted hearts resulted in improved cardiac function. CDCs have been tested safely in an initial phase-1 clinical trial in patients after myocardial infarction. Whether or not CDCs are superior to purified populations, for example, c-kit+ cardiac stem cells, or to gene therapy approaches for cardiac regeneration remains to be evaluated. Lucio Barile, Mihaela Gherghiceanu, Laurenţiu M. Popescu, Tiziano Moccetti, and Giuseppe Vassalli Copyright © 2013 Lucio Barile et al. All rights reserved. Sun, 28 Apr 2013 16:46:32 +0000 http://www.hindawi.com/journals/sci/2013/658480/ ST elevation myocardial infarction (STEMI) is associated with an increased risk for congestive heart failure and long-term mortality despite the widespread use of thrombolysis and catheter-based revascularization. The need for improved post-STEMI therapies has led to a surge of novel therapeutics, especially regenerative approaches using autologous mononuclear cells. Indeed, the past decade has been marked by a number of human trials studying the safety and efficacy of progenitor cell delivery in the post-STEMI setting. While a variety of cell types and delivery techniques have been utilized, directed therapy to the infarct-related artery has been the most widely used approach. From over 1300 subjects randomized in these studies, there is sufficient evidence to conclude that cell therapy after STEMI is uniformly safe, while the efficacy of this intervention for improving outcomes is less clear. Recent meta-analyses have highlighted the importance of both timing of cell delivery, as well as the type, quantity, and mobility of delivered cells as determinants of response. Here, we show the case in which higher doses of CD34+ cells, which are more potent in terms of their migratory capacity, offer the best hope for preserving cardiac function following STEMI. Joseph C. Poole and Arshed A. Quyyumi Copyright © 2013 Joseph C. Poole and Arshed A. Quyyumi. All rights reserved. Wed, 24 Apr 2013 08:07:26 +0000 http://www.hindawi.com/journals/sci/2013/509593/ Mariya P. Dobreva, Larissa Lhoest, Paulo N. G. Pereira, Lieve Umans, Anne Camus, Susana M. Chuva de Sousa Lopes, and An Zwijsen Copyright © 2013 Mariya P. Dobreva et al. All rights reserved. Tue, 16 Apr 2013 19:17:50 +0000 http://www.hindawi.com/journals/sci/2013/360573/ Pluripotent stem cells present an extraordinary powerful tool to investigate embryonic development in humans. Essentially, they provide a unique platform for dissecting the distinct mechanisms underlying pluripotency and subsequent lineage commitment. Modest information currently exists about the expression and the role of ion channels during human embryogenesis, organ development, and cell fate determination. Of note, small and intermediate conductance, calcium-activated potassium channels have been reported to modify stem cell behaviour and differentiation. These channels are broadly expressed throughout human tissues and are involved in various cellular processes, such as the after-hyperpolarization in excitable cells, and also in differentiation processes. To this end, human induced pluripotent stem cells (hiPSCs) generated from plucked human hair keratinocytes have been exploited in vitro to recapitulate endoderm formation and, concomitantly, used to map the expression of the SK channel (SKCa) subtypes over time. Thus, we report the successful generation of definitive endoderm from hiPSCs of ectodermal origin using a highly reproducible and robust differentiation system. Furthermore, we provide the first evidence that SKCas subtypes are dynamically regulated in the transition from a pluripotent stem cell to a more lineage restricted, endodermal progeny. Anett Illing, Marianne Stockmann, Narasimha Swamy Telugu, Leonhard Linta, Ronan Russell, Martin Müller, Thomas Seufferlein, Stefan Liebau, and Alexander Kleger Copyright © 2013 Anett Illing et al. All rights reserved. Mon, 15 Apr 2013 11:06:58 +0000 http://www.hindawi.com/journals/sci/2013/784629/ Ion channels are involved in a large variety of cellular processes including stem cell differentiation. Numerous families of ion channels are present in the organism which can be distinguished by means of, for example, ion selectivity, gating mechanism, composition, or cell biological function. To characterize the distinct expression of this group of ion channels we have compared the mRNA expression levels of ion channel genes between human keratinocyte-derived induced pluripotent stem cells (hiPSCs) and their somatic cell source, keratinocytes from plucked human hair. This comparison revealed that 26% of the analyzed probes showed an upregulation of ion channels in hiPSCs while just 6% were downregulated. Additionally, iPSCs express a much higher number of ion channels compared to keratinocytes. Further, to narrow down specificity of ion channel expression in iPS cells we compared their expression patterns with differentiated progeny, namely, neurons and cardiomyocytes derived from iPS cells. To conclude, hiPSCs exhibit a very considerable and diverse ion channel expression pattern. Their detailed analysis could give an insight into their contribution to many cellular processes and even disease mechanisms. Leonhard Linta, Marianne Stockmann, Qiong Lin, André Lechel, Christian Proepper, Tobias M. Boeckers, Alexander Kleger, and Stefan Liebau Copyright © 2013 Leonhard Linta et al. All rights reserved. Wed, 03 Apr 2013 19:12:12 +0000 http://www.hindawi.com/journals/sci/2013/985285/ Multipotent stromal cells can be isolated from a variety of different tissues in the body. In contrast to stromal cells from the adult bone marrow (BM) or adipose tissue, cord blood (CB) multipotent stromal cells (MSC) are biologically younger. Since first being described by our group, delta like 1 homologue (DLK-1) was determined as a discriminating factor between the distinct cord blood-derived subpopulations: the unrestricted somatic stromal cells (USSC), which lack adipogenic differentiation capacity, and the BM MSC-like CB MSC. In this study, experiments assessing the haematopoiesis-supporting capacity and molecular biological analyses were conducted and clearly confirmed different properties. Compared to CB MSC, USSC lead to a higher expansion of haematopoietic cells and in addition express significantly higher levels of insulin-like growth factor binding protein 1 (IGFBP1), but lower levels of IGF2. The data presented here also indicate that DLK-1 might not be the sole factor responsible for the inhibition of adipogenic differentiation potential in USSC but nevertheless indicates a biological diversity among cord blood-derived stromal cells. Simone Maria Kluth, Teja Falk Radke, and Gesine Kögler Copyright © 2013 Simone Maria Kluth et al. All rights reserved. Wed, 27 Mar 2013 14:20:23 +0000 http://www.hindawi.com/journals/sci/2013/589139/ In contrast to the pluripotent embryonic stem cells (ESCs) which are able to give rise to all cell types of the body, mammalian adult stem cells (ASCs) appeared to be more limited in their differentiation potential and to be committed to their tissue of origin. Recently, surprising new findings have contradicted central dogmas of commitment of ASCs by showing their plasticity to differentiate across tissue lineage boundaries, irrespective of classical germ layer designations. The present paper supports the plasticity of the bone marrow stem cells (BMSCs), bringing the most striking and the latest evidences of the transdifferentiation properties of the bone marrow hematopoietic and mesenchymal stem cells (BMHSCs, and BMMSCs), the two BM populations of ASCs better characterized. In addition, we report the possible mechanisms that may explain these events, outlining the clinical importance of these phenomena and the relative problems. Ivana Catacchio, Simona Berardi, Antonia Reale, Annunziata De Luisi, Vito Racanelli, Angelo Vacca, and Roberto Ria Copyright © 2013 Ivana Catacchio et al. All rights reserved. Wed, 27 Mar 2013 11:17:20 +0000 http://www.hindawi.com/journals/sci/2013/656839/ Human mesenchymal stem cells (hMSCs) have gained intense research interest due to their immune-modulatory, tissue differentiating, and homing properties to sites of inflammation. Despite evidence demonstrating the biodistribution of infused hMSCs in target organs using static fluorescence imaging or whole-body imaging techniques, surprisingly little is known about how hMSCs behave dynamically within host tissues on a single-cell level in vivo. Here, we infused fluorescently labeled clinical-grade hMSCs into immune-competent mice in which neutrophils and monocytes express a second fluorescent marker under the lysozyme M (LysM) promoter. Using intravital two-photon microscopy (TPM), we were able for the first time to capture dynamic interactions between hMSCs and LysM+ granulocytes in the calvarium bone marrow of recipient mice during systemic LPS challenge in real time. Interestingly, many of the infused hMSCs remained intact despite repeated cellular contacts with host neutrophils. However, we were able to observe the destruction and subsequent phagocytosis of some hMSCs by surrounding granulocytes. Thus, our imaging platform provides opportunities to gain insight into the biology and therapeutic mechanisms of hMSCs in vivo at a single-cell level within live hosts. Jay T. Myers, Deborah S. Barkauskas, and Alex Y. Huang Copyright © 2013 Jay T. Myers et al. All rights reserved. Tue, 26 Mar 2013 14:04:15 +0000 http://www.hindawi.com/journals/sci/2013/245695/ Ex vivo expansion of haematopoetic cells by application of specific cytokines is one approach to overcome boundaries in cord blood transplantation due to limited numbers of haematopoetic stem cells. While many protocols describe an effective increase of total cell numbers and the amount of CD34-positive cells, it still remains unclear if and how the procedure actually affects the cells’ properties. In the presented publications, CD34-positive cells were isolated from cord blood and expanded for up to 7 days in media supplemented with stem cell factor (SCF), thrombopoietin (THPO), interleukin 6 (IL-6), and fms-related tyrosine kinase 3 ligand (FLT3lg). At days 3 and 7, expanded cells were harvested and analyzed by flow cytometry and quantitative proteomics. 2970 proteins were identified, whereof proteomic analysis showed 440 proteins significantly changed in abundance during ex vivo expansion. Despite the fact that haematopoetic cells still expressed CD34 on the surface after 3 days, major changes in regard to the protein profile were observed, while further expansion showed less effect on the proteome level. Enrichment analysis of biological processes clearly showed a proteomic change toward a protein biosynthesis phenotype already within the first three days of expression. Heiner Falkenberg, Teja Falk Radke, Gesine Kögler, and Kai Stühler Copyright © 2013 Heiner Falkenberg et al. All rights reserved. Tue, 19 Mar 2013 15:29:15 +0000 http://www.hindawi.com/journals/sci/2013/496218/ Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expanded in vitro. Moreover, their ability to modulate immune responses makes them an even more attractive candidate for regenerative medicine as allogeneic transplant of these cells is feasible without a substantial risk of immune rejection. MSCs secrete various immunomodulatory molecules which provide a regenerative microenvironment for a variety of injured tissues or organ to limit the damage and to increase self-regulated tissue regeneration. Autologous/allogeneic MSCs delivered via the bloodstream augment the titers of MSCs that are drawn to sites of tissue injury and can accelerate the tissue repair process. MSCs are currently being tested for their potential use in cell and gene therapy for a number of human debilitating diseases and genetic disorders. This paper summarizes the current clinical and nonclinical data for the use of MSCs in tissue repair and potential therapeutic role in various diseases. Devang M. Patel, Jainy Shah, and Anand S. Srivastava Copyright © 2013 Devang M. Patel et al. All rights reserved. Tue, 19 Mar 2013 11:27:03 +0000 http://www.hindawi.com/journals/sci/2013/353105/ Background. Regenerative therapy is an emerging treatment modality. To determine migration and retention of implanted cells, it is crucial to develop noninvasive tracking methods. The aim was to determine ex vivo magnetic resonance imaging (MRI) detection limits of ultrasmall superparamagnetic iron-oxide (USPIO) labeled mesenchymal stromal cells (MSCs). Materials and Methods. 248 gel-phantoms were constructed and scanned on a 1.5T MRI-scanner. Phantoms contained human MSCs preincubated with USPIO nanoparticles for 2, 6, or 21 hours using 5 or 10 μg USPIO/105 MSCs. In addition, porcine hearts were scanned after injection of USPIO labeled MSCs. Results. Using 21 h incubation time and 10 μg USPIO/105 MSCs, labeled cells were clearly separated from unlabeled cells on MRI using 250.000 (), 500.000 (), and 1.000.000 MSCs (). At lower incubation times and doses, neither labeled nor unlabeled cells could be separated. In porcine hearts labeled, but not unlabeled, MSCs were identified on MRI. Conclusions. As few as 250.000 MSCs can be detected on MRI using 21 h incubation time and 10 μg USPIO/105 MSCs. At lower incubation times and doses, several million cells are needed for MRI detection. USPIO labeled cells can be visualized by MRI in porcine myocardial tissue. Anders Bruun Mathiasen, Louise Hansen, Tina Friis, Carsten Thomsen, Kishore Bhakoo, and Jens Kastrup Copyright © 2013 Anders Bruun Mathiasen et al. All rights reserved. Mon, 11 Mar 2013 17:15:36 +0000 http://www.hindawi.com/journals/sci/2013/205878/ We tested the hypothesis that transient microinjury to the brain elicits cellular and humoral responses that stimulate hippocampal neurogenesis. Brief stereotaxic insertion and removal of a microneedle into the right hippocampus resulted in (a) significantly increased expression of granulocyte-colony stimulating factor (G-CSF), the chemokine MIP-1a, and the proinflammatory cytokine IL12p40; (b) pronounced activation of microglia and astrocytes; and (c) increase in hippocampal neurogenesis. This study describes immediate and early humoral and cellular mechanisms of the brain’s response to microinjury that will be useful for the investigation of potential neuroprotective and deleterious effects of deep brain stimulation in various neuropsychiatric disorders. Shijie Song, Shuojing Song, Chuanhai Cao, Xiaoyang Lin, Kunyu Li, Vasyl Sava, and Juan Sanchez-Ramos Copyright © 2013 Shijie Song et al. All rights reserved. Mon, 11 Mar 2013 16:10:47 +0000 http://www.hindawi.com/journals/sci/2013/132642/ Mesenchymal stem cells (MSCs) are prototypical adult stem cells with the capacity for self-renewal and differentiation with a broad tissue distribution. MSCs not only differentiate into types of cells of mesodermal lineage but also into endodermal and ectodermal lineages such as bone, fat, cartilage and cardiomyocytes, endothelial cells, lung epithelial cells, hepatocytes, neurons, and pancreatic islets. MSCs have been identified as an adherent, fibroblast-like population and can be isolated from different adult tissues, including bone marrow (BM), umbilical cord, skeletal muscle, and adipose tissue. MSCs secrete factors, including IL-6, M-CSF, IL-10, HGF, and PGE2, that promote tissue repair, stimulate proliferation and differentiation of endogenous tissue progenitors, and decrease inflammatory and immune reactions. In this paper, we focus on the role of BM-derived MSCs in organ repair. Ming Li and Susumu Ikehara Copyright © 2013 Ming Li and Susumu Ikehara. All rights reserved. Mon, 11 Mar 2013 09:22:34 +0000 http://www.hindawi.com/journals/sci/2013/960958/ The characterization of human stem cells for the usability in regenerative medicine is particularly based on investigations regarding their differentiation potential in vivo. In this regard, the chicken embryo model represents an ideal model organism. However, the access to the chicken embryo is only achievable by windowing the eggshell resulting in limited visibility and accessibility in subsequent experiments. On the contrary, ex ovo-culture systems avoid such negative side effects. Here, we present an improved ex ovo-cultivation method enabling the embryos to survive 13 days in vitro. Optimized cultivation of chicken embryos resulted in a normal development regarding their size and weight. Our ex ovo-approach closely resembles the development of chicken embryos in ovo, as demonstrated by properly developed nervous system, bones, and cartilage at expected time points. Finally, we investigated the usability of our method for trans-species transplantation of adult stem cells by injecting human neural crest-derived stem cells into late Hamburger and Hamilton stages (HH26–HH28/E5—E6) of ex ovo-incubated embryos. We demonstrated the integration of human cells allowing experimentally easy investigation of the differentiation potential in the proper developmental context. Taken together, this ex ovo-method supports the prolonged cultivation of properly developing chicken embryos enabling integration studies of xenografted mammalian stem cells at late developmental stages. Timo Schomann, Firas Qunneis, Darius Widera, Christian Kaltschmidt, and Barbara Kaltschmidt Copyright © 2013 Timo Schomann et al. All rights reserved. Thu, 07 Mar 2013 09:45:03 +0000 http://www.hindawi.com/journals/sci/2013/823912/ The assessment of nonviable haematopoietic cells by Annexin V staining method in flow cytometry has recently been published by Duggleby et al. Resulting in a better correlation with the observed colony formation in methylcellulose assays than the standard ISHAGE protocol, it presents a promising method to predict cord blood potency. Herein, we applied this method for examining the parameters during processing which potentially could affect cord blood viability. We could verify that the current standards regarding time and temperature are sufficient, since no significant difference was observed within 48 hours or in storage at up to . However, the addition of DMSO for cryopreservation alone leads to an inevitable increase in nonviable haematopoietic stem cells from initially 14.8% ± 4.3% to at least 30.6% ± 5.5%. Furthermore, CFU-assays with varied seeding density were performed in order to evaluate the applicability as a quantitative method. The results revealed that only in a narrow range reproducible clonogenic efficiency (ClonE) could be assessed, giving at least a semiquantitative estimation. We conclude that both Annexin V staining method and CFU-assays with defined seeding density are reliable means leading to a better prediction of the final potency. Especially Annexin V, due to its fast readout, is a practical tool for examining and optimising specific steps in processing, while CFU-assays add a functional confirmation. Teja Falk Radke, David Barbosa, Richard Charles Duggleby, Riccardo Saccardi, Sergio Querol, and Gesine Kögler Copyright © 2013 Teja Falk Radke et al. All rights reserved. Sun, 03 Mar 2013 15:42:36 +0000 http://www.hindawi.com/journals/sci/2013/246134/ Mesenchymal stem cells (MSCs) are somatic cells with a dual capacity for self-renewal and differentiation, and diverse therapeutic applicability, both experimentally and in the clinic. These cells can be isolated from various human tissues that may differ anatomically or developmentally with relative ease. Heterogeneity due to biological origin or in vitro manipulation is, nevertheless, considerable and may equate to differences in qualitative and quantitative characteristics which can prove crucial for successful therapeutic use. With this in mind, in the present study we have evaluated the proliferation kinetics and phenotypic characteristics of MSCs derived from two abundant sources, that is, fetal umbilical cord matrix (Wharton's jelly) and adult adipose tissue (termed WJSC and ADSC, resp.) during prolonged in vitro expansion, a process necessary for obtaining cell numbers sufficient for clinical application. Our results show that WJSC are derived with relatively high efficiency and bear a substantially increased proliferation capacity whilst largely sustaining the expression of typical immunophenotypic markers, whereas ADSC exhibit a reduced proliferation potential showing typical signs of senescence at an early stage. By combining kinetic with phenotypic data we identify culture thresholds up to which both cell types maintain their stem properties, and we discuss the practical implications of their differences. I. Christodoulou, F. N. Kolisis, D. Papaevangeliou, and V. Zoumpourlis Copyright © 2013 I. Christodoulou et al. All rights reserved. Sun, 03 Mar 2013 15:22:05 +0000 http://www.hindawi.com/journals/sci/2013/319489/ Head and neck squamous cell carcinoma (HNSCC) is one of the world’s top ten most common cancers. Current survival rates are poor with only 50% of patients expected to survive five years after diagnosis. The poor survival rate of HNSCC is partly attributable to the tendency for diagnosis at the late stage of the disease. One of the reasons for treatment failure is thought to be related to the presence of a subpopulation of cells within the tumour called cancer stem cells (CSCs). CSCs display stem cell-like characteristics that impart resistance to conventional treatment modalities and promote tumour initiation, progression, and metastasis. Specific markers for this population have been investigated in the hope of developing a deeper understanding of their role in the pathogenesis of HNSCC and elucidating novel therapeutic strategies. Aidan G. Major, Luke P. Pitty, and Camile S. Farah Copyright © 2013 Aidan G. Major et al. All rights reserved. Mon, 25 Feb 2013 08:58:35 +0000 http://www.hindawi.com/journals/sci/2013/463031/ Umbilical cord blood banking efforts have increased dramatically in the past two decades in response to increasing demand for alternative sources of blood stem cells to support patients requiring hematopoietic stem cell transplantation. Transplant centres have accumulated increasing expertise in their understanding of umbilical cord blood characteristics that are associated with improved outcome following transplantation. These characteristics and factors can assist transplant centres in selecting cord blood units from the worldwide inventory of banked units. Umbilical cord blood banks, therefore, need to remain agile in adjusting the inventory of the banks to address shifts or changes in the needs of transplant centres. Public umbilical cord blood banks face the challenge of building inventory while managing limited resources and are faced with decisions regarding which units can be stored and which units that have been collected should be discarded or used for other endeavours such as research. To this end, we sought to review parameters influencing the decision to bank a collected cord blood unit. In this paper, we will address parameters associated with graft potency and address other factors that guide the decision to bank collected units. David Allan, Tanya Petraszko, Heidi Elmoazzen, and Susan Smith Copyright © 2013 David Allan et al. All rights reserved. Wed, 20 Feb 2013 16:12:36 +0000 http://www.hindawi.com/journals/sci/2013/124834/ Umbilical cord blood (UCB) is used increasingly in allogeneic transplantation. The size of units remains limiting, especially for adult recipients. Whether modest improvements in the yield of cells surviving storage and thawing allow more patients to proceed to transplant was examined. The impact of improved cell yield on the number of available UCB units was simulated using 21 consecutive anonymous searches. The number of suitable UCB units was calculated based on hypothetical recipient weight of 50 kg, 70 kg, and 90 kg and was repeated for a 10%, 20%, and 30% increase in the fraction of cells surviving storage. Increasing the percentage of cells that survive storage by 30% lowered the threshold of cells needed to achieve similar engraftment rates and increased numbers of UCB units available for patients weighing 50 (), 70 (), and 90 kg (), controlling for differences in HLA compatibility. Moreover, if recipients were 90 kg, 12 out of 21 patients had access to at least one UCB unit that met standard criteria, which increased to 19 out of 21 patients () when the fraction of cells surviving storage and thawing increased by 30%. Modest increases in the yield of cells in banked UCB units can significantly increase donor options for adult patients undergoing HSCT. Natasha Kekre, Jennifer Philippe, Ranjeeta Mallick, Susan Smith, and David Allan Copyright © 2013 Natasha Kekre et al. All rights reserved.