Cancer stem cells (CSC) have been investigated as prognostic markers in oral squamous cell carcinoma (OSCC). However, an assessment of the reporting quality of these studies has not been performed yet. The aim of this study was to describe the reporting quality of prognostic studies involving CSCs and OSCC, focusing mainly on the immunohistochemical reproducibility. By means a systematic review, 34 articles were selected. Analyses of both general reporting quality and immunohistochemistry technique were performed by using checklists for multiple aspects related to study reproducibility. A total of 21 different CSC markers were cited in the selected studies, evaluated by means of a wide range of antibodies, most of them (40.3%) without clone description. Discrepancies in intracellular immunolabeling were noted for some markers. The mean global score for general quality assessment revealed limits in the quality of the articles. The main problems were related to lack of report on OSCC characteristics and treatment, sample size rationale, and sensitivity analysis or internal validation of the markers. Although there was a high frequency of studies having "good or very good" score for immunohistochemistry reproducibility, the frequency of articles with "poor or very poor" score for individual items was expressive, mainly for description of immunolabeling analysis (38.2% of the studies were poorly described). In conclusion, although there is a significant range of CSC markers with promising results for prognosis of OSCC, the inadequate reporting of important sections in the published studies, including immunohistochemistry technique, may limit the quality of the investigation.

Adoptive infusion of chimeric antigen receptor transduced T- cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results.

The popularity of adipose-derived cell therapy has increased over the last decade, and the number of studies published annually is growing. However, concerns regarding safety in the setting of previous malignancy or the use of allogeneic cells have been raised. We therefore aimed to systematically review all clinical studies using adipose-derived cell therapy to identify reported adverse events with a special focus on risk of thromboembolic, immunological, and oncological safety concerns. Our systematic search resulted in 70 included studies involving more than 1,400 patients that were treated with adipose-derived cell therapy. Safety assessment method was not described in 32 of the included studies. For studies involving systemic or cardiac administration, one case of pulmonary thromboembolism and cases of both myocardial and cerebral infarctions were described. In the setting of allogeneic cell therapy studies, where the production of specific antibodies toward donor cells was examined, it was noted that 19%-34% of patients develop antibodies, but the consequence of this is unknown. With regard to oncological safety, only one case of breast cancer recurrence was identified out of 121 patients. Adipose-derived cell therapy has so far shown a favorable safety profile, but safety assessment description has, in general, been of poor quality, and only adverse events that are looked for will be found. We encourage future studies to maintain a strong focus on the safety profile of cell therapy, so its safeness can be confirmed. Stem Cells Translational Medicine 2017;6:1786-1794.

Autologous fat grafting is a common procedure for soft-tissue reconstruction but is associated with a graft resorption rate ranging from 20% to 80%. To improve the fat graft survival rate, a new technique, called cell-assisted lipotransfer (CAL), was developed. With CAL, fat is injected along with adipose-derived stromal cells that are assumed to improve fat survival rate. We conducted an evidence-based meta-analysis to evaluate the efficacy and safety of CAL as compared with conventional autologous fat grafting (non-CAL). The databases MEDLINE (via PubMed), Cochrane Library, EBSCO, Web of Science, and EMBASE were searched for reports of clinical trials, case series, and cohorts available from 2008 to 2016. We conducted a meta-analysis of the efficacy of CAL with data analysis concerning fat survival rate. The incidence of complications and the need for multiple procedures were evaluated to determine the safety of CAL. We identified 25 studies (696 patients) that were included in the systematic review; 16 studies were included in the meta-analysis to evaluate the efficacy of CAL. The fat survival rate was significantly higher with CAL than non-CAL (64% vs. 44%, p < .0001) independent of injection site (breast and face). This benefit of CAL was significant for only injection volumes <100 ml (p = .03). The two groups did not differ in frequency of multiple procedures after fat grafting, but the incidence of complications was greater with CAL than non-CAL (8.4% vs. 1.5%, p = .0019). The CAL method is associated with better fat survival rate than with conventional fat grafting but only for small volumes of fat grafting (<100 ml). Nonetheless, the new technique is associated with more complications and did not reduce the number of surgical procedures needed after the first fat grafting. More prospective studies are required to draw clinical conclusions and to demonstrate the real benefit of CAL as compared with common autologous fat grafting.

The purpose of the present investigation is to conduct a systematic review of the literature to review the clinical results of platelet rich plasma (PRP) and mesenchymal stem cell treatments (MSC) (biologics) for articular cartilage lesions and osteoarthritis of the knee.

Adipose tissue-derived stem cells (ASCs) are known to be tissue-healing promoters due to their cellular plasticity and secretion of paracrine factors. Cultured ASC sheets provide a novel method of ASC application and can retain ASCs at the targeted tissue. The purpose of this systematic review is to evaluate preclinical studies using ASC sheet transplantation therapy for promoting tissue healing. First, we searched databases to identify studies of ASC sheet therapy in different experimental animal models, and then determined the quality score of studies using SYRCLE's risk bias tool. A total of 18 included studies examined the role of ASC sheets on tissue healing and function in models for myocardial infarction, dilated cardiomyopathy, full-thickness skin wounds, hind limb ischemia, esophageal strictures, and oral ulcers. ASC sheet application after myocardial infarction improved survival rate, cardiac function, and capillary density and reduced the extent of fibrosis. Application of ASC sheets to a full-thickness skin wound decreased the wound size and stimulated wound maturation. In the hind limb ischemia model, ASC sheet application improved limb perfusion and capillary density, and decreased the amount of ischemic tissue and inflammation. ASC sheet application to mucosal wounds of the digestive tract accelerated wound healing and decreased the degree of stricture and fibrosis. Taken together, transplanted ASC sheets had a positive effect on tissue healing and reconstruction in these preclinical studies. The reported favorable effects of ASC sheet therapy in various tissue healing applications may be implemented in future translational studies. It is suggested that future preclinical animal model studies of ASC sheet therapy should concern standardization of culture techniques and investigate the mechanisms of action. In addition, clearly indicated experimental setups according to the SYRCLE's guidelines should improve study quality and validity.

To examine the evidence behind the use of concentrated bone marrow aspirate (cBMA) in cartilage, bone, and tendon repair; establish proof of concept for the use of cBMA in these biologic environments; and provide the level and quality of evidence substantiating the use of cBMA in the clinical setting.

One of the methods employed to improve healing of damaged tissues is the use of cellular based therapies. A number of regenerative medicine based strategies, from in vitro expanded mesenchymal stem cells (MSCs) to "one-step" procedures using bone marrow (BM) in toto (BM aspirate; BMA) or BM concentrate (BMC), have been developed. Recently, orthopedic researchers focused their attention on the clinical therapeutic potential of BMC and BMA for musculoskeletal regeneration. BMA is reported as an excellent source of cells and growth factors. However, the quality of BM harvest and aspirate is extremely technique-dependent and, due to the presence of megakaryocytes and platelets, BMA is prone to clot. BMA clot formation is usually considered a complication hampering the procedures on both BMC preparation and MSC expansion. Therefore, different protocols have been developed to avoid and/or degrade clots. However, from a biological point of view there is a strong rationale for the use of BMA clot for tissue engineering strategies. This descriptive systematic literature review summarizes preclinical and clinical studies dealing the use of BMA clot for orthopedic procedures and provided some evidence supporting its use as a cell based therapy for cartilage and bone regeneration. Despite these results, there are still few preclinical and clinical studies that carefully evaluate the safety and efficacy of BMA clot in orthopedic procedures. Thus, implementing biological knowledge and both preclinical and clinical studies could help researchers and clinicians to understand if BMA clots can really be considered a possible therapeutic tool.

In a systematic review, to present an overview of the current situation in the field of tissue engineering of urinary bladder related to the use of cell lines pre-cultured on matrices. The selection of eligible publications was conducted according to the method described in the article Glybochko P.V. et al. "Tissue engineering of urinary bladder using acellular matrix." At the final stage, studies investigating the application of matrices with human and animal cell lines were analyzed. Contemporary approaches to using cell-based tissue engineering of the bladder were analyzed, including the formation of 3D structures from several types of cells, cell layers and genetic modification of injected cells. The most commonly used cell lines are urothelial cells, mesenchymal stem cells and fibroblasts. The safety and efficacy of any types of composite cell structures used in the cell-based bladder tissue engineering has not been proven sufficiently to warrant clinical studies of their usefulness. The results of cystoplasty of rat bladder are almost impossible to extrapolate to humans; besides, it is difficult to predict possible side effects. For the transition to clinical trials, additional studies on relevant animal models are needed.

Fetal bovine serum (FBS) is the most commonly used supplement for ex vivo expansion of human mesenchymal stem cells (hMSCs) for bone tissue engineering applications. However, from a clinical standpoint, it is important to substitute animal-derived products according to current good manufacturing practice (cGMP) guidelines. Humanized alternatives to FBS include three categories of products: human serum (HS), human platelet derivatives (HPDs)-including platelet lysate (PL) or platelet releasate (PR), produced by freeze/thawing or chemical activation of platelet concentrates, respectively, and chemically defined media (serum-free) (CDM). In this systematic literature review, the in vitro and in vivo osteogenic potential of hMSCs expanded in humanized (HS-, HPD-, or CDM-supplemented) media versus hMSCs expanded in FBS-supplemented media, was compared. In addition, PL and PR were compared in terms of their growth factor (GF)/cytokine-content and cell-culture efficacy. When using either 10-20% autologous or pooled HS, 3-10% pooled HPDs or CDM supplemented with GFs, in comparison with 10-20% FBS, a majority of studies reported similar or superior in vitro proliferation and osteogenic differentiation, and in vivo bone formation in ectopic or orthotopic rodent models. Moreover, a trend for higher GF content was observed in PL versus PR, although evidence for cell culture efficacy is limited. In summary, humanized supplements seem at least equally effective as FBS for hMSC expansion and osteogenic differentiation. Although pooled HPDs appear to be the most favorable supplement for large-scale hMSC expansion, further efforts are needed to standardize the preparation and composition of these products in compliance with cGMP standards.

Adult mesenchymal stem cells (MSCs) were first isolated from bone marrow by Friedenstein in 1976. These cells were clonogenic, non-haematopoietic, and able to replicate extensively in vitro. The fields of regenerative medicine and tissue engineering have grown dramatically since their inception. In the decades since, MSCs have been identified from mesoderm-, endoderm- and ectoderm-derived tissues. In light of our ageing population, the need for effective cell-based therapies for tissue repair and regeneration is ever-expanding.

Stem cell therapy (SCT) for the treatment of Crohn's disease (CD) is still in its infancy, and whether SCT is associated with improved outcomes is unclear. We performed a meta-analysis to evaluate the efficacy and safety of patients receiving SCT.

We performed a systematic review to identify all original publications describing the asymmetric inheritance of cellular organelles in normal animal eukaryotic cells and to critique the validity and imprecision of the evidence. Searches were performed in Embase, MEDLINE and Pubmed up to November 2015. Screening of titles, abstracts and full papers was performed by two independent reviewers. Data extraction and validity were performed by one reviewer and checked by a second reviewer. Study quality was assessed using the SYRCLE risk of bias tool, for animal studies and by developing validity tools for the experimental model, organelle markers and imprecision. A narrative data synthesis was performed. We identified 31 studies (34 publications) of the asymmetric inheritance of organelles after mitotic or meiotic division. Studies for the asymmetric inheritance of centrosomes (n = 9); endosomes (n = 6), P granules (n = 4), the midbody (n = 3), mitochondria (n = 3), proteosomes (n = 2), spectrosomes (n = 2), cilia (n = 2) and endoplasmic reticulum (n = 2) were identified. Asymmetry was defined and quantified by variable methods. Assessment of the statistical reliability of the results indicated only two studies (7%) were judged to have low concern, the majority of studies (77%) were 'unclear' and five (16%) were judged to have 'high concerns'; the main reasons were low technical repeats (<10). Assessment of model validity indicated that the majority of studies (61%) were judged to be valid, ten studies (32%) were unclear and two studies (7%) were judged to have 'high concerns'; both described 'stem cells' without providing experimental evidence to confirm this (pluripotency and self-renewal). Assessment of marker validity indicated that no studies had low concern, most studies were unclear (96.5%), indicating there were insufficient details to judge if the markers were appropriate. One study had high concern for marker validity due to the contradictory results of two markers for the same organelle. For most studies the validity and imprecision of results could not be confirmed. In particular, data were limited due to a lack of reporting of interassay variability, sample size calculations, controls and functional validation of organelle markers. An evaluation of 16 systematic reviews containing cell assays found that only 50% reported adherence to PRISMA or ARRIVE reporting guidelines and 38% reported a formal risk of bias assessment. 44% of the reviews did not consider how relevant or valid the models were to the research question. 75% reviews did not consider how valid the markers were. 69% of reviews did not consider the impact of the statistical reliability of the results. Future systematic reviews in basic or preclinical research should ensure the rigorous reporting of the statistical reliability of the results in addition to the validity of the methods. Increased awareness of the importance of reporting guidelines and validation tools is needed for the scientific community.

Tissue engineering of corporal tissue is a new development in otherwise untreatable erectile dysfunction and in urethral reconstructions to treat hypospadias or severe urethral stricture disease. Multiple complications can arise with the current treatments, whereas engineered tissue, if well vascularized and existing of autologous cells, may lead to better results. The aim of this review was to provide an overview of literature on cell-seeded-based tissue engineering of corporal penile tissue. A literature search was performed following the PRISMA guidelines. Papers describing cell-seeded tissue engineering of corporal tissue were included. Studies using different techniques, such as intracavernous injection were excluded. Fifteen articles were included in the review. Twelve of these studies described engineering of the corpus cavernosum in animal models. Two articles were found on engineering of animal corpus spongiosum and one article on engineering of the human glans. Both synthetic scaffolds and biological scaffolds were used. The advantage of a biological, acellular scaffold was that the native, complex architecture of corporal tissue was maintained. Most studies used endothelial and smooth muscle cells from corporal origin, but stem cells were also investigated. Furthermore, dynamic culturing achieved an improved cell content and functionality. This review has summarized the developments in tissue engineering of corpus cavernosum and spongiosum tissue. Functional tissue has been developed in animal studies with the use of seeded cells on scaffolds. This knowledge will form a basis for the development of tissue engineering of corporal tissue for clinical applications.

Periodontitis is a destructive inflammatory disorder of the periodontium caused by the destruction of periodontal tissues namely the PDL, cementum, alveolar bone, and gingiva. Once these tissues are lost, the foremost goal of periodontal therapy is to regenerate the diseased tissues if possible to their original form, architecture, and function. Various regenerative procedures were employed and still a gap was found in achieving the goal. As stem cells are characterized by their ability to self-renew and differentiate to produce specialized cells, there could be a possibility of using them for regenerative therapy. Recently, dental tissues such as the PDL, the dental pulp and the tooth follicle have been recognized as readily available sources of adult stem cells.

Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2-5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50-80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms "uterine carcinosarcoma", "uterine Malignant Mixed Müllerian Tumors", "target therapies", "angiogenesis therapy", "cancer stem cell therapy", "prognostic biomarker", and "novel antibody-drug". Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2) open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

The purpose of this article is to systematically review the methods of mobilization, isolation and characterization of stem cells from peripheral blood and to discuss their potential therapeutic applications for bone tissue regeneration.

Granulocyte-colony stimulating factor (G-CSF) mobilizes and increases the amount of hematopoietic stem cells in peripheral blood, enabling its harvest by few apheresis procedures. The pegylated G-CSF has longer half-life and is given once only, which is more comfortable for patients, whereas the non-pegylated requires multiple daily injection because of its short half-life. We summarized results of randomized trials comparing the efficacy and safety of pegylated and non-pegylated G-CSF for peripheral blood stem cell mobilization. We searched the Cochrane CENTRAL, MEDLINE, EMBASE, and two conference proceedings. Two authors made the selection, extracted data and evaluated methodological quality using GRADE independently. We used random-effects model for meta-analysis. We found 3956 records and retrieved 47 full texts. We included eight randomized trials with a total number of 554 randomized and 532 analyzed subjects. The meta-analysis included five trials because not all trials reported the same outcomes. Pooling data from two studies shows no evidence for a difference in the successful mobilization rate (CD34+ cell ≥ 2 × 106 /kg collected) between pegfilgrastim 6 mg (early administration) and filgrastim 5 µg/kg/day (147 participants; risk ratio (RR) 0.87, 95% confidence interval (95%CI) 0.67-1.11; P = .26). Pooling data from three studies shows no difference in the incidence of adverse events between pegylated and non-pegylated G-CSF (170 participants; RR 0.86, 95%CI 0.34-2.17; P = .75). No difference found on the quantity of CD34+ cells collected, number of apheresis procedure in successful mobilization, level of peak PB CD34+ cells achieved, and day of neutrophil and platelet engraftment.

Cell therapy holds the most promising for acute and chronic deleterious respiratory diseases. However, the safety and tolerance for lung disorders are controversy.

Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rates for most metastatic cancers are still quite low, and the process of developing a new anti-cancer drug is costly and extremely time-consuming. Therefore, new strategies that target the survival pathways that provide efficient and effective results at an affordable cost are being considered. One such approach incorporates repurposing therapeutic agents initially used for the treatment of different diseases other than cancer. This approach is effective primarily when the FDA-approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA-approved, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy, thereby benefiting the "medically underserved". In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden. In this systematic review, we discuss important pathways commonly targeted in cancer therapy. Furthermore, we also review important repurposed or primary anti-cancer agents that have gained popularity in clinical trials and research since 2012.