Human immunodeficiency virus (HIV)-infected individuals have a cardiovascular disease risk that is almost thrice than that of their HIV-uninfected counterparts. Given the critical role of endothelial progenitor cells (EPCs) in vascular homeostasis and arterial repair postinjury, coupled with their strength as biomarkers predictive of cardiovascular events, interest has arisen in characterizing EPCs in the context of HIV infection. We conducted a systematic review of the literature to determine the current state of knowledge on EPCs in the context of HIV infection. Herein, we summarize the pertinent findings of these studies and discuss important differences in the subpopulations of EPCs examined and the methodologies used for their enumeration which likely contributed to the heterogeneity observed across studies.

Stem cell therapies have significant potential to treat spinal cord injury (SCI), but it remains difficult to translate these therapies from 'bench to bedside'. Identifying barriers to translation and understanding how these barriers are viewed by stakeholders in the field of stem cell research are key steps to clinical translation. The Stem Cell Global Blueprint Conference, held in Toronto (ON, Canada) presented a unique opportunity to analyze the perspectives of multiple stakeholders on the future of stem cell therapies for SCI treatment. This article is an analysis of data collected at the conference, including a consensus-building process and pre- and in-conference questionnaires. The authors used these data to assess current perceptions of stem cell research and compared the findings with the literature. The authors identified the major barriers according to a wide range of stakeholders and what strategies they suggested to overcome these obstacles, with the aim of forwarding discussion on stem cell research. It is not a systematic review of the area, but rather a presentation of expert opinion with literature citations to give context and support to their arguments and suggestions. The authors believe that the international SCI community is ready for larger-scale clinical translation, which will require the continued cooperation of all stakeholders in the stem cell and SCI communities.

The management and treatment of bone defects caused by trauma, non-union, tumors and disease poses a major clinical problem. Limitations with autograft and allograft have led to research into tissue engineering of bone graft using scaffolds and mesenchymal stem cells.

Meniscal injuries are one of the common sports injuries and their natural healing is limited. Removal of injured meniscus alters knee biomechanics and predisposes patients to osteoarthritis. Tissue engineered meniscus provides a novel approach for the treatment of severe meniscus injury. The aim of this review is to review preclinical studies that used cell based approaches for tissue engineered meniscus. Studies were assessed for inclusion following a search in PubMed, UK PubMed central and Embase. All preclinical studies that used cell based approaches for meniscus regeneration were included in the study. Nineteen articles that used cellular approaches were reviewed. The cell types used were mesenchymal stem cells (derived from bone marrow or synovium), meniscal fibrochondrocytes, chondrocytes and bone marrow stromal cells. One study used xenogeneic bone marrow derived mesenchymal stem cells. Sixteen out of nineteen studies showed better tissue regeneration with cell based approaches when compared to acellular controls. The review included preclinical studies. The diversity of the studies made it impossible to adhere to full guidelines or perform a meta-analysis. Overall,experiments have demonstrated superior tissue integration and favourable biochemical properties of the regenerated tissues compared to acellular techniques. Few approaches however, have measured the chondroprotective ability at preclinical testing.

The management of extensive bone defects in the setting of fracture repair, non-union and revision arthroplasty are challenging problems. The supply of harvestable autologous bone graft is limited, with an associated morbidity, and there fore a need exists for a better solution in large defects. The use of stem cells is an evolving field of research, with different potential applications, ranging from simple injection of cells to tissue engineering using osteogenic cells seeded on to a scaffold. This systematic review aims to collate the published preclinical and clinical studies investigating the potential use of stem cells for bone repair.

The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration.

The first Phase I study of autologous tolerogenic dendritic cells (Tol-DCs) in Type 1 diabetes (T1D) patients was recently completed. Pancreatic islet transplantation is an effective therapy for T1D, and infusion of Tol-DCs can control diabetes development while promoting graft survival. In this study, we aim to systematically review islet allograft survival following infusion of Tol-DCs induced by different methods, to better understand the mechanisms that mediate this process.

The meta-analysis of recent small animal experiments of mesenchymal stem/stromal cells (MSC) therapy for impaired kidney could provide significant clues to design large animal experiments as well as human clinical trials.

Mesenchymal stromal cells (MSCs, "adult stem cells") have been widely used experimentally in a variety of clinical contexts. There is interest in using these cells in critical illness, however, the safety profile of these cells is not well known. We thus conducted a systematic review of clinical trials that examined the use MSCs to evaluate their safety.

Using a systematic approach, the authors evaluated the current utilization, safety, and effectiveness of cellular therapies for traumatic spinal cord injuries (SCIs) in humans.

Allogeneic haematopoietic stem cell transplantation (HSCT) is an established treatment for many malignant and non-malignant haematological disorders. Graft-versus-host disease (GVHD), a condition frequently occurring after HSCT, is the result of host tissues being attacked by donor immune cells. One strategy for the prevention of GVHD is the administration of anti-thymocyte globulins (ATG), a set of polyclonal antibodies directed against a variety of immune cell epitopes, leading to immunosuppression and immunomodulation.

Transplantation therapies aimed at repairing neurodegenerative and neuropathological conditions of the central nervous system (CNS) have utilized and tested a variety of cell candidates, each with its own unique set of advantages and disadvantages. The use and popularity of each cell type is guided by a number of factors including the nature of the experimental model, neuroprotection capacity, the ability to promote plasticity and guided axonal growth, and the cells' myelination capability. The promise of stem cells, with their reported ability to give rise to neuronal lineages to replace lost endogenous cells and myelin, integrate into host tissue, restore functional connectivity, and provide trophic support to enhance and direct intrinsic regenerative ability, has been seen as a most encouraging step forward. The advent of the induced pluripotent stem cell (iPSC), which represents the ability to "reprogram" somatic cells into a pluripotent state, hails the arrival of a new cell transplantation candidate for potential clinical application in therapies designed to promote repair and/or regeneration of the CNS. Since the initial development of iPSC technology, these cells have been extensively characterized in vitro and in a number of pathological conditions and were originally reported to be equivalent to embryonic stem cells (ESCs). This review highlights emerging evidence that suggests iPSCs are not necessarily indistinguishable from ESCs and may occupy a different "state" of pluripotency with differences in gene expression, methylation patterns, and genomic aberrations, which may reflect incomplete reprogramming and may therefore impact on the regenerative potential of these donor cells in therapies. It also highlights the limitations of current technologies used to generate these cells. Moreover, we provide a systematic review of the state of play with regard to the use of iPSCs in the treatment of neurodegenerative and neuropathological conditions. The importance of balancing the promise of this transplantation candidate in the light of these emerging properties is crucial as the potential application in the clinical setting approaches. The first of three sections in this review discusses (A) the pathophysiology of spinal cord injury (SCI) and how stem cell therapies can positively alter the pathology in experimental SCI. Part B summarizes (i) the available technologies to deliver transgenes to generate iPSCs and (ii) recent data comparing iPSCs to ESCs in terms of characteristics and molecular composition. Lastly, in (C) we evaluate iPSC-based therapies as a candidate to treat SCI on the basis of their neurite induction capability compared to embryonic stem cells and provide a summary of available in vivo data of iPSCs used in SCI and other disease models.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI) imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib) in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients.

Stem cell therapy holds great promise in medicine, but clinical development should be based on a sound understanding of potential weaknesses in supporting experimental data. The aim of this article was to provide a systematic overview of evidence relating to the efficacy of stem cell-based therapies in animal models of stroke to foster the clinical application of stem cell-based therapies and to inform the design of large-scale clinical trials. We conducted a systematic search for reports of experiments using stem cells in animal models of cerebral ischaemia, and performed DerSimmonian and Laird random effects meta-analysis. We assessed the impact of study characteristics, of publication bias and of measures to reduce bias. We identified 6059 publications, 117 met our prespecified inclusion criteria. One hundred eighty-seven experiments using 2332 animals described changes in structural outcome and 192 experiments using 2704 animals described changes in functional outcome. Median study quality score was 4 (interquartile range 3 to 6) and less than half of studies reported randomization or blinded outcome assessment; only three studies reported a sample size calculation. Nonrandomized studies gave significantly higher estimates of improvement in structural outcome, and there was evidence of a significant publication bias. For structural outcome autologous (i.e. self-derived) stem cells were more effective than allogeneic (donor-derived) cells, but for functional outcome, the reverse was true. A significant dose-response relationship was observed only for structural outcome. For structural outcome, there was an absolute reduction in efficacy of 1·5% (-2·4 to -0·6) for each days delay to treatment; functional outcome was independent of the time of administration. While stem cells appear to be of some benefit in animal models of stroke the internal and external validity of this literature is potentially confounded by poor study quality and by publication bias. The clinical development of stem cell-based therapies, in stroke and elsewhere, should acknowledge these potential weaknesses in the supporting animal data.

Over the past 30 years, nanotechnology has evolved dramatically. It has captured the interest of variety of fields from computing and electronics to biology and medicine. Recent discoveries have made invaluable changes to future prospects in nanomedicine; and introduced the concept of theranostics. This term offers a patient specific 'two in one' modality that comprises of diagnostic and therapeutic tools. Not only nanotechnology has shown great impact on improvements in drug delivery and imaging techniques, but also there have been several ground-breaking discoveries in regenerative medicine.

In the management of sensorineural hearing loss, effective therapy for degenerated hair cells, third order neurons, ganglions, dendrites and synaptic areas of the vestibulo-cochleo-cerebral pathway remains an enigma. Transplantation of stem and progenitor cells appears to be an emerging potential solution, and is the focus of this review.

The term tissue engineering is the technology that combines cells, engineering and biological/synthetic material in order to repair, replace or regenerate biological tissues such as bone, muscle, tendons and cartilage. The major human applications of tissue engineering are: skin, bone, cartilage, corneas, blood vessels, left mainstem bronchus and urinary structures. In this systematic review several criteria were identified as the most desirable characteristics of an ideal scaffold. These state that an ideal scaffolds needs to be biodegradable, possess mechanical strength, be highly porous, biocompatible, non-cytotoxic, non antigentic, stuitable for cell attachment, proliferation and differentiation, flexible and elastic, three dimensional, osteoconductive and support the transport of nutrients and metabolic waste. Subsequently, studies reporting on the various advantages and disadvantages of using collagen based scaffolds in musculoskeletal and cartilage tissue engineering were identified. The purpose of this review is to 1) provide a list of ideal characteristics of a scaffold as identified in the literature 2) identify different types of biological protein-based collagen scaffolds used in musculoskeletal and cartilage tissue engineering 3) assess how many of the criteria each scaffold type meets 4) weigh different scaffolds against each other according to their relative properties and shortcomings. The rationale behind this approach is that the ideal scaffold material has not yet been identified. Hence, this review will define how many of the identified ideal characteristics are fulfilled by natural collagen-based scaffolds and address the shortcomings of its use as found in the literature.

Fracture healing is a complex physiological process. Local vascularity at the site of the fracture has been established as one of the most important factors influencing the healing process, and lack of vascularity has been implicated in atrophic non unions. Existing research has primarily involved utilising Mesenchymal Stem Cells (MSCs) to augment bone healing but there remains much scope to explore the role of stem cells in the vascularisation process. Endothelial Progenitor Cells (EPCs) and other Endothelial Cellular populations (ECs) could constitute a valid alternative to MSCs. This systematic review is examining the importance of co-implantation of MSCs and EPCs/ECs for bone healing. A literature search was performed using the Cochrane Library, OVID Medline, OVID EMBASE and Google Scholar, searching for combinations of the terms EPCs, Endothelial progenitor cells, angiogenesis, fracture, bone and healing. Finally 18 articles that fulfilled our criteria were included in this review. ECs could be of value for the treatment of critical size bone defects as they are known to be capable of forming ectopic, vascularised bone. The co-implantation of ECs with MSCs is more intriguing when we take into account the vast array of complex reciprocal interactions between ECs and MSCs.

The aim is to review and discuss the strategies available for the regeneration of tooth tissues based on principles of tissue engineering.

High and continuously increasing research activity related to different aspects of pathogenesis, epidemiology, diagnosis and treatment of glioblastoma has been performed between 2006 and 2010. Different measures of impact, visibility and quality of published research are available, each with its own pros and cons. For this review, article citation rate was chosen. Articles were identified through systematic search of the abstract database PubMed followed by analyses of total number of citations and proportion of highly cited articles, arbitrarily defined as those with ≥100, 50-99, and 25-49 citations, respectively (citation database Scopus). Overall 5831 scientific articles on the subject were published during this time period. 1.5% of all articles accumulated at least 100 citations, 3.2% were cited between 50 and 99 times, and 7.5% were cited between 25 and 49 times. Among the 10 most cited articles, 7 reported on genomic analyses, molecular subclasses of glioblastoma and/or stem cells. Overall, 18 randomized clinical trials were published between 2006 and 2010, including those with phase II design. Thirty-nine percent of them accumulated at least 50 citations and 72% were cited at least 25 times. In general, annual citation rate appeared to gradually increase during the first 2-3 years after publication before reaching high levels. A large variety of preclinical and clinical topics achieved at least 25 citations. However, areas such as quality of life, side effects, and end-of-life care were underrepresented. Efforts to increase their visibility might be warranted.