Tooth extraction as a part of dental care provides an opportunity to obtain dental pulp stem cells that could constitute new therapeutic tools for craniofacial bone and teeth repair. However, the use of tooth as a biological sample of human origin must comply with legislation and ethical rules.

The intranasal route for drug delivery is rapidly evolving as a viable means for treating selected central nervous system (CNS) conditions. We aimed to identify studies pertaining to the application of intranasal drug administration for the treatment of primary CNS tumors. A systematic literature review was conducted to identify all studies published in the English language pertaining to intranasal therapy for CNS neoplasms, and/or general mechanisms and pharmacokinetics regarding targeted intranasal CNS drug delivery. A total of 194 abstracts were identified and screened. Thirty-seven studies met inclusion criteria. Of these, 21 focused on intranasal treatment of specific primary CNS tumors, including gliomas (11), meningiomas (1), and pituitary adenomas (4). An additional 16 studies focused on general mechanisms of intranasal therapy and drug delivery to the CNS using copolymer micelles, viral vectors, and nanoparticles. Inhaled compounds/substances investigated included perillyl alcohol, vesicular stomatitis virus, parvovirus, telomerase inhibitors, neural stem and progenitor cells, antimetabolites, somatostatin analogues, and dopamine agonists. Radiolabeling, CSF concentration measurement, imaging studies, and histological examination were utilized to clarify the mechanism and distribution by which drugs were delivered to the CNS. Successful drug delivery and tumor/symptom response was reported in all 21 tumor-specific studies. The intranasal route holds tremendous potential as a viable option for drug delivery for CNS neoplasms. A variety of antitumoral agents may be delivered via this route, thereby potentially offering a more direct delivery approach and ameliorating the adverse effects associated with systemic drug delivery.

Granulocytic sarcoma also called myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid leukemia. It is observed during the course of myeloproliferative disorders especially in chronic myeloid leukemia and myelodysplastic syndromes. In some rare circumstances, it is detected before clinical signs of leukemia or other diseases. When the bone marrow biopsy reveals no other hematologic malignancies, the granulocytic sarcoma is described as nonleukemic, primary or isolated. It is observed at any part of the body but the most common locations are soft tissues, bone, peritoneum and lymph nodes. Presenting signs or symptoms are mainly due to mass effect of the tumor and dysfunction of the organ, or the tissue that is affected. The diagnosis is performed by biopsy of the tumor. The tumor consists of immature granulocytic cells, which could be documented by H&E, immunohistochemistry, and flow cytometric methods. Fluorescence in-situ hybridization and molecular analysis are also performed. The optimal time and type of treatment is not clear. Surgery could be an option especially for tumors, which cause organ dysfunction and/or obstruction. Systemic treatment should be considered in all patients because without systemic treatment, relapses and progression to acute myeloid leukemia is the ultimate fate of the disease in many cases. Cytarabine-containing remission-induction chemotherapies have been the most applied therapeutic strategies, but it is not clear whether the consolidation therapies are required or not, and what kind of regimens are appropriate. The role of hematopoietic stem cell transplantation (HSC) as a consolidation regimen is not clear, but, after the relapse of the disease with or without bone marrow involvement, HSC transplantation should be considered in suitable patients after the reinduction performed by AML chemotherapies. There is only limited data about the role of radiotherapy in these patients. It could be used in patients with relapsed disease, organ dysfunction which should be quickly relieved and inadequate response to chemotherapy. The effect of radiotherapy on overall survival is not known. New prospective studies and clinical trials are needed to generate guidelines for the treatment of primary granulocytic sarcomas.

Spinal cord injury (SCI) is a devastating condition that causes substantial morbidity and mortality and for which no treatments are available. Stem cells offer some promise in the restoration of neurological function. We used systematic review, meta-analysis, and meta-regression to study the impact of stem cell biology and experimental design on motor and sensory outcomes following stem cell treatments in animal models of SCI. One hundred and fifty-six publications using 45 different stem cell preparations met our prespecified inclusion criteria. Only one publication used autologous stem cells. Overall, allogeneic stem cell treatment appears to improve both motor (effect size, 27.2%; 95% Confidence Interval [CI], 25.0%-29.4%; 312 comparisons in 5,628 animals) and sensory (effect size, 26.3%; 95% CI, 7.9%-44.7%; 23 comparisons in 473 animals) outcome. For sensory outcome, most heterogeneity between experiments was accounted for by facets of stem cell biology. Differentiation before implantation and intravenous route of delivery favoured better outcome. Stem cell implantation did not appear to improve sensory outcome in female animals and appeared to be enhanced by isoflurane anaesthesia. Biological plausibility was supported by the presence of a dose-response relationship. For motor outcome, facets of stem cell biology had little detectable effect. Instead most heterogeneity could be explained by the experimental modelling and the outcome measure used. The location of injury, method of injury induction, and presence of immunosuppression all had an impact. Reporting of measures to reduce bias was higher than has been seen in other neuroscience domains but were still suboptimal. Motor outcomes studies that did not report the blinded assessment of outcome gave inflated estimates of efficacy. Extensive recent preclinical literature suggests that stem-cell-based therapies may offer promise, however the impact of compromised internal validity and publication bias mean that efficacy is likely to be somewhat lower than reported here.

The aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra-articular injections of platelet-rich plasma (PRP).

To investigate the correlation between CD133-positive non-small cell lung cancer (NSCLC) and clinicopathological features and its impact on survival.

Blood vessels transport blood to deliver oxygen and nutrients. Vascular diseases such as atherosclerosis may result in obstruction of blood vessels and tissue ischemia. These conditions require blood vessel replacement to restore blood flow at the macrocirculatory level, and angiogenesis is critical for tissue regeneration and remodeling at the microcirculatory level. Vascular tissue engineering has focused on addressing these two major challenges. We provide a systematic review on various approaches for vascular graft tissue engineering. To create blood vessel substitutes, bioengineers and clinicians have explored technologies in cell engineering, materials science, stem cell biology, and medicine. The scaffolds for vascular grafts can be made from native matrix, synthetic polymers, or other biological materials. Besides endothelial cells, smooth muscle cells, and fibroblasts, expandable cells types such as adult stem cells, pluripotent stem cells, and reprogrammed cells have also been used for vascular tissue engineering. Cell-seeded functional tissue-engineered vascular grafts can be constructed in bioreactors in vitro. Alternatively, an autologous vascular graft can be generated in vivo by harvesting the capsule layer formed around a rod implanted in soft tissues. To overcome the scalability issue and make the grafts available off-the-shelf, nonthrombogenic vascular grafts have been engineered that rely on the host cells to regenerate blood vessels in situ. The rapid progress in the field of vascular tissue engineering has led to exciting preclinical and clinical trials. The advancement of micro-/nanotechnology and stem cell engineering, together with in-depth understanding of vascular regeneration mechanisms, will enable the development of new strategies for innovative therapies.

Traumatic spinal cord injury (SCI) is a devastating event with huge personal and societal costs. A limited number of treatments exist to ameliorate the progressive secondary damage that rapidly follows the primary mechanical impact. Mesenchymal stem or stromal cells (MSCs) have anti-inflammatory and neuroprotective effects and may thus reduce secondary damage after administration. We performed a systematic review with quantitative syntheses to assess the evidence of MSCs versus controls for locomotor recovery in rat models of traumatic SCI, and identified 83 eligible controlled studies comprising a total of 1,568 rats. Between-study heterogeneity was large. Fifty-three studies (64%) were reported as randomised, but only four reported adequate methodologies for randomisation. Forty-eight studies (58%) reported the use of a blinded outcome assessment. A random-effects meta-analysis yielded a difference in behavioural Basso-Beattie-Bresnahan (BBB) locomotor score means of 3.9 (95% confidence interval [CI] 3.2 to 4.7; P<0.001) in favour of MSCs. Trial sequential analysis confirmed the findings of the meta-analyses with the upper monitoring boundary for benefit being crossed by the cumulative Z-curve before reaching the diversity-adjusted required information size. Only time from intervention to last follow-up remained statistically significant after adjustment using multivariate random-effects meta-regression modelling. Lack of other demonstrable explanatory variables could be due to insufficient meta-analytic study power. MSCs would seem to demonstrate a substantial beneficial effect on locomotor recovery in a widely-used animal model of traumatic SCI. However, the animal results should be interpreted with caution concerning the internal and external validity of the studies in relation to the design of future clinical trials.

During recent years, attention has been given to the potential of therapeutic approaches using stem cells obtained from dental pulp tissue. The aim of this study, therefore, was to give an overview of the papers produced during the last 10 years that have described the use of stem cells obtained from human deciduous teeth in cell therapy or bioengineering. The PubMed database was investigated from January 2002 until July 2011 and the papers published during this period were analyzed according to criteria previously established, using the methodology of systematic review. The measurements were done using "stem cell" as the primary keyword, and "human deciduous teeth dental pulp cell" and "human exfoliated deciduous teeth" as the secondary keywords. Four hundred and seventy-five papers were found. The first screening resulted in 276 papers, from which 84 papers were selected. However, only 11 of them attained the aim proposed in our approach. There were few scientific studies related to direct therapeutic application using stem cells of human deciduous teeth and none of them had been applied to humans. However, the results indicated important and promising applications of the pulp stem-cells in cell therapy and bioengineering as demonstrated by studies in animal models of muscular dystrophy, Parkison's disease, and lupus erythematosus.

This review of literature was aimed to assess in vivo experiments which have evaluated the efficacy of dental pulp stem cells (DPSCs) for bone regeneration.

Numerous clinical trials have demonstrated early reductions in cardiovascular events occurring independently of the lipid-lowering effects of statins. These pleiotropic effects have been attributed to antiinflammatory properties, to atherosclerotic plaque stabilization, and more recently to mobilization of endothelial progenitor cells (EPCs). Our aim was to evaluate the evidence supporting statin-induced EPC mobilization in humans. We, therefore, performed a computerized literature search and systematic review of randomized trials to determine the effect of statin therapy and statin dosing on circulating EPC numbers. Our literature search identified 10 studies including 479 patients which met inclusion criteria with publication dates ranging from 2005 to 2011. Seven studies compared statin to nonstatin regimens whereas 3 studied low versus high-dose statin therapy. Reported increases in EPC number ranged from 25.8% to 223.5% with a median reported increase of 70.2% when compared to nonstatin regimens with 7 of 10 studies reporting significant increases. Considerable heterogeneity exists in regard to patient population, statin regimens, and the definition of an EPC within the identified studies. In conclusion, randomized studies in humans suggest that statin therapy mobilizes EPCs into the circulation. Larger randomized studies using uniform definitions are needed to definitively establish this effect.

Systematic review.

To evaluate bone marrow stem cell treatment (BMSC) in patients with ischemic heart disease (IHD) and no option of revascularization.

Dilated cardiomyopathy (DCM) is the most common form of nonischemic cardiomyopathy worldwide and can lead to sudden cardiac death and heart failure. Despite ongoing advances made in the treatment of DCM, improvement of outcome remains problematic. Stem cell therapy has been extensively studied in preclinical and clinical models of ischemic heart disease, showing potential benefit. DCM is associated with a major health burden, and few studies have been performed on cell therapy for DCM. In this systematic review we aimed to provide an overview of preclinical and clinical studies performed on cell therapy for DCM.

This study evaluated clinical outcomes following intraoperative use of adult mesenchymal stem cells (MSCs) in various oral reconstructive procedures. PubMed was searched without language restrictions from 2000 to 2011 using the search words stem cell, oral surgery, tissue engineering, sinus lift, bone regeneration and combinations of these. Inclusion criteria were intraoperative use of MSCs in the study design. Reference lists of the articles found were searched for other related studies. Eighteen clinical trials using MSCs for sinus augmentation were found: five case reports on the repair of large bony defects and six studies on ridge augmentation and healing of alveolar sockets after third molar extraction. The findings suggest that MSCs are capable of producing in vivo bone, re-establishing lost tissue and facilitating placement of dental implants. Use of MSCs would reduce patient morbidity because of a less stressful harvesting technique than that of autogenous bone. The majority of clinical trials indicate that MSCs can produce bone in vivo. However, a satisfactory outcome was not seen in all studies, and due to the diversity of study designs, a 'golden approach' cannot be determined. Before use of MSCs can be considered as a first-choice treatment, more predictable outcomes and better long-term prognoses need to be established. Conventional bone grafting remains the gold standard.

An important goal of stem cell research in orthopaedics is to develop clinically relevant techniques that could be applied to heal cartilage or joint pathology. Stem cell treatment in orthopaedics for joint pathology is promising since these cells have the ability to modulate different processes in the various tissues of the joint simultaneously. The non life-threatening nature of musculoskeletal system disorders makes safety of stem cell therapy a necessary prerequisite.

Cell-based approaches, utilizing adult mesenchymal stem cells (MSCs), are reported to overcome the limitations of conventional bone augmentation procedures.

This review aimed to examine the effects of exercise training on mobilization of endothelial progenitor cells (EPCs) in patients with cardiovascular disease and to discuss the possible mechanisms involved in the process. A computer-aided search on PubMed and PEDro was conducted to identify relevant studies published up to June 2012. Two reviewers independently selected studies for inclusion and extracted data, namely, quantitative assessment of circulating EPCs. Of the 88 identified studies, 13 met the inclusion criteria. The 13 studies enrolled 648 participants, including patients with chronic heart failure, peripheral artery disease, and coronary artery disease. The exercise characteristics varied largely across the studies: exercise duration ranged from 2 wks to 6 mos, session duration ranged from 20 to 60 mins, and exercise intensity was usually calculated using the maximal heart rate (ranging from 75% to 85%) or the peak/maximum oxygen consumption (60%-70%). All studies used aerobic exercise. The great majority of the 13 studies reported significant effects of different exercise regimens on the number of circulating EPCs. In summary, exercise training seems to increase the number of circulating EPCs, which could contribute to vascular regeneration and angiogenesis. These positive effects of chronic exercise seem to be closely related to the bioavailability of nitric oxide, including increased activity of endothelial nitric oxide synthase and antioxidant enzymes, and activation of matrix metalloproteinase 9.

There is considerable interest in translating laboratory advances in neuronal regeneration following spinal cord injury (SCI). A multimodality approach has been advocated for successful functional neuronal regeneration. With this goal in mind several biomaterials have been employed as neuronal bridges either to support cellular transplants, to release neurotrophic factors, or to do both. A systematic review of this literature is lacking. Such a review may provide insight to strategies with a high potential for further investigation and potential clinical application.

The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer.