The epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs), but the clinical and prognostic significance of EpCAM in gastric cancer (GC) remains disputable. Motivated by heterogeneous and inconclusive results, we conducted a systematic review and meta-analysis to systematically summarize and elucidate the association between EpCAM overexpression and GC patients.

This systematic review aims to evaluate mesenchymal stem cells (MSC) periodontal regenerative potential in animal models. MEDLINE, EMBASE and LILACS databases were searched for quantitative pre-clinical controlled animal model studies that evaluated the effect of local administration of MSC on periodontal regeneration. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. Twenty-two studies met the inclusion criteria. Periodontal defects were surgically created in all studies. In seven studies, periodontal inflammation was experimentally induced following surgical defect creation. Differences in defect morphology were identified among the studies. Autogenous, alogenous and xenogenous MSC were used to promote periodontal regeneration. These included bone marrow-derived MSC, periodontal ligament (PDL)-derived MSC, dental pulp-derived MSC, gingival margin-derived MSC, foreskin-derived induced pluripotent stem cells, adipose tissue-derived MSC, cementum-derived MSC, periapical follicular MSC and alveolar periosteal cells. Meta-analysis was not possible due to heterogeneities in study designs. In most of the studies, local MSC implantation was not associated with adverse effects. The use of bone marrow-derived MSC for periodontal regeneration yielded conflicting results. In contrast, PDL-MSC consistently promoted increased PDL and cementum regeneration. Finally, the adjunct use of MSC improved the regenerative outcomes of periodontal defects treated with membranes or bone substitutes. Despite the quality level of the existing evidence, the current data indicate that the use of MSC may provide beneficial effects on periodontal regeneration. The various degrees of success of MSC in periodontal regeneration are likely to be related to the use of heterogeneous cells. Thus, future studies need to identify phenotypic profiles of highly regenerative MSC populations.

Osteonecrosis of the femoral head (ONFH) is associated with regional loss of cells within bone, often resulting in pain and mechanical collapse. Our purpose was to analyze the cell-therapies used in clinical trials for the treatment of ONFH with regard to (1) cell-sources, (2) collection techniques, (3) cell-processing, (4) qualitative and quantitative characterizations, and (5) delivery methods.

Osteoarthritis results in irreparable loss of articular cartilage. Due to its avascular nature and low mitotic activity, cartilage has little intrinsic capacity for repair. Cartilage loss leads to pain, physical disability, movement restriction, and morbidity. Various treatment strategies have been proposed for cartilage regeneration, but the optimum treatment is yet to be defined. Tissue engineering with engineered constructs aimed towards developing a suitable substrate may help in cartilage regeneration by providing the mechanical, biological and chemical support to the cells. The use of scaffold as a substrate to support the progenitor cells or autologous chondrocytes has given promising results. Leakage of cells, poor cell survival, poor cell differentiation, inadequate integration into the host tissue, incorrect distribution of cells, and dedifferentiation of the normal cartilage are the common problems in tissue engineering. Current research is focused on improving mechanical and biochemical properties of scaffold to make it more efficient. The aim of this review is to provide a critical discussion on existing challenges, scaffold type and properties, and an update on ongoing recent developments in the architecture and composition of scaffold to enhance the proliferation and viability of mesenchymal stem cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2343-2354, 2017.

Mesenchymal stem cells (MSCs) are an attractive source for regenerative medicine because they are easily accessible through minimally invasive methods and have the potential to enhance liver regeneration (LG) and improve liver function, following partial hepatectomy (PH) and acute or chronic liver injury. A systematic review of the literature was conducted for articles published up to September 1st, 2016, using the MEDLINE database. The keywords that were used in various combinations were as follows: "Mesenchymal stem cells", "transplantation", "stem cells", "adipose tissue derived stem cells", "bone marrow-derived stem cells", "partial hepatectomy", "acute liver failure", "chronic liver failure", "liver fibrosis", "liver cirrhosis", "rats", "mice", and "liver regeneration". All introduced keywords were searched for separately in MeSH Database to control relevance and terminological accuracy and validity. A total of 41 articles were identified for potential inclusion and reviewed in detail. After a strict selection process, a total of 28 articles were excluded, leaving 13 articles to form the basis of this systematic review. MSCs transplantation promoted LG and improved liver function. Furthermore, MSCs had the ability to differentiate in hepatocyte-like cells, increase survival, and protect hepatocytes by paracrine mechanisms. MSCs transplantation may provide beneficial effects in the process of LG after PH and acute or chronic liver injury. They may represent a new therapeutic option to treat posthepatectomy acute liver failure.

Peritoneal fibrosis remains a serious complication of long-term peritoneal dialysis. Stem cell therapy is an innovative field of scientific investigation with potential for clinical application. Here, we systematically reviewed the studies to determine whether stem cell based therapy could improve the peritoneal fibrosis in experimental models of peritoneal fibrosis.

This systematic review provides an overview of publications concerning pharmacogenetic research in pediatric patients with medulloblastoma and low-grade glioma.

Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult.

The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous.

Bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity as no effective treatment is available to date. This calls for the exploration of new therapeutic options like cell therapy, which is already effective for various human (lung) disorders. We systematically searched the MEDLINE, Embase, and Web of Science databases from the earliest date till January 2017 and included original studies on the perinatal use of cell-based therapies (i.e. cells and/or cell-derivatives) to treat BDP in animal models. Fourth publications describing 47 interventions were retrieved. Newborn mice/rats raised in a hyperoxic environment were studied in most interventions. Different cell types - either intact cells or their conditioned medium - were administered, but bone marrow and umbilical cord blood derived mesenchymal stem cells were most prevalent. All studies reported positive effects on outcome parameters including alveolar and vascular morphometry, lung function, and inflammation. Cell homing to the lungs was demonstrated in some studies, but the therapeutic effects seemed to be mostly mediated via paracrine modulation of inflammation, fibrosis and angiogenesis.

Advancements in cellular reprogramming techniques have made it possible to directly study brain cells from patients with neuropsychiatric disorders. We have systematically reviewed the applications of induced pluripotent stem cells (IPSCs) and their neural derivatives in understanding the biological basis of schizophrenia.

Stem cell injection for knee osteoarthritis (KOA) is an emerging new therapy, and we aimed to review its evidence of efficacy.

The applications for fat grafting have increased recently, within both regenerative and reconstructive surgery. Although fat harvesting, processing and injection techniques have been extensively studied and standardised, this has not had a big impact on the variability of outcome following fat grafting. This suggests a possible larger role of patient characteristics on adipocyte and adipose-derived stem cell (ADSC) viability and function. This systematic review aims to collate current evidence on the effect of patient factors on adipocyte and ADSC behaviour.

Several non-biological materials are currently being used to increase the alveolar bone volume to support dental implants. Recently, stem cell therapy has emerged as a promising biological substitute or adjuvant to enhance bone healing. In order to determine if stem cell therapy has enough clinical evidence to bone ridge augmentation in humans, a systematic review and meta-analysis were conducted. Two independent investigators searched the Entrez PubMed, SCOPUS and Web of Science databases for eligible randomized clinical trials that describe stem cell therapies for alveolar bone formation. The included studies were evaluated for risk of bias. A random-effects meta-analysis model was used to evaluate the percentage of bone formation in the selected studies. Heterogeneity was evaluated using the Cochrane Chi 2 and I 2. Nine eligible trials were included. These studies presented an overall unclear risk of bias. A comparison between the lower heterogeneity studies and the long term observational outcomes showed a slight tendency to enhance bone formation. High heterogeneity between the included studies was observed. The lack of outcome standardization made a wide-ranging comparison difficult. The application of stem cells in oral surgery and implantology appears to be promising although more standardized study designs, increased samples and long-term observations are needed to strength the clinical evidence that stem cell therapy is effective for alveolar bone formation.

The current systematic review investigated the results of application of some of the most commonly used scaffolds in conjugation with stem cells and growth factors in animal and clinical studies.

The introduction of mesenchymal stromal cells (MSCs) has changed the management of Crohn's fistula, while it remains controversial. The aim of this study was to provide an overview of efficacy and optimum state of MSCs treatment on Crohn's fistula.

Cell-therapy has been promoted among the therapeutic arsenal that can aid in bone formation and remodeling, in early stages of osteonecrosis of the femoral head (ONFH). The purpose of this systematic review was to assess the evidence supporting the (1) clinical efficacy; (2) structural modifying effect, as evaluated radiographically; (3) revision rates; and (4) safety of cell-therapy for the treatment of ONFH.

Today, autogenous bone graft (ABG) is still considered as the gold standard for joint fusion. Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) which is of chemotactic and mitogenic to mesenchymal stem cells and possesses outstanding osteogenetic potentials has been used for ankle and foot fusion in recent years. The goal of this article is to evaluate the safety and efficacy of rhPDGF-BB versus ABG in foot and ankle fusion. The PubMed MEDLINE, EMBASE, Web of Science, and Cochrane Library were systematic searched. Finally, three randomized controlled trials (RCTs) with 634 patients were enrolled in this study. Results of radiologic effectiveness which included CT and radiographic union rates revealed that there was no significant difference between rhPDGF-BB approach and ABG approach. Analysis of clinical results held the same outcomes expect that ABG group was superior in long-term Short Form-12 physical component scores. The pooled results also demonstrated that rhPDGF-BB was as safe as ABG in foot and ankle surgery. However, autograft harvesting procedure has some drawbacks such as donor-site pain and morbidity, additional operation time, blood loss, and scarring, which can be overcome by rhPDGF-BB. Thus, rhPDGF-BB is a viable alternative to autograft in foot and ankle fusion surgery. Yet, more high-quality RCTs with long-term follow-up are still required to make the final conclusion.

The maintenance of viable and functional pancreatic islets is crucial for successful islet transplantation from brain-dead donors. To overcome islet quality loss during culture, some studies have co-cultured islets with mesenchymal stem/stromal cells (MSC). However, it is still uncertain if MSC-secreted factors are enough to improve islet quality or if a physical contact between MSCs and islets is needed. Therefore, we performed a systematic review and meta-analysis to clarify the effect of different culture contact systems of islets with MSCs on viability and insulin secretion outcomes. Pubmed and Embase were searched. Twenty studies fulfilled the eligibility criteria and were included in the qualitative synthesis and/or meta-analysis. For both outcomes, pooled weighted mean differences (WMD) between islet cultured alone (control group) and the co-culture condition were calculated. Viability mean was higher in islets co-cultured with MSCs compared with islet cultured alone [WMD = 18.08 (95% CI 12.59-23.57)]. The improvement in viability was higher in islets co-cultured in indirect or mixed contact with MSCs than in direct physical contact (P <0.001). Moreover, the mean of insulin stimulation index (ISI) was higher in islets from co-culture condition compared with islet cultured alone [WMD = 0.83 (95% CI 0.54-1.13)], independently of contact system. Results from the studies that were analyzed only qualitatively are in accordance with meta-analysis data. Co-culture of islets with MSCs has the potential for protecting islets from injury during culture period. Moreover, culture time appears to influence the beneficial effect of different methods of co-culture on viability and function of islets.

Mesenchymal stromal cells (MSCs) are considered to have a modest benefit on left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI). However, the optimal injection timing and dose needed to induce beneficial cardiac effects are unknown. The purpose of this meta-analysis was to identify an optimal MSC transplantation time and cell dose in the setting of AMI to achieve better clinical endpoints.