Tendon pathologies are a group of musculoskeletal conditions frequently seen in clinical practice. They can be broadly classified into traumatic, degenerative and overuse-related tendinopathies. Rotator cuff tears, Achilles tendinopathy and tennis elbow are common examples of these conditions. Conventional treatments have shown inconsistent outcomes and might fail to provide satisfactory clinical improvement. With the growing trend towards the use of mesenchymal stem cells (MSCs) in other branches of medicine, there is an increasing interest in treating tendon pathologies using the bone marrow MSC. In this article, we provide a systematic literature review documenting the current status of the use of bone marrow aspirate concentrate (BMAC) for the treatment of tendon pathologies. We also asked the question on the safety of BMAC and whether there are potential complications associated with BMAC therapy. Our hypothesis is that the use of BMAC provides safe clinical benefit when used for the treatment of tendinopathy or as a biological augmentation of tendon repair. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist while preparing this systematic review. A literature search was carried out including the online databases of PubMed, EMBASE, ClinicalTrial.gov and the Cochrane Library from 1960 to the end of May 2015. Relevant studies were selected and critically appraised. Data from eligible studies were extracted and classified per type of tendon pathology. We included 37 articles discussing the application and use of BMAC for the treatment of tendon pathologies. The Critical Appraisal Skills Program (CASP) appraisal confirmed a satisfactory standard of 37 studies. Studies were sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (n = 18), where five studies looked at the evaluation of aspiration techniques (n = 5), augmentation of rotator cuff tears (n = 5), augmentation of tendo-achilles tendon (n = 1), treatment of gluteal tendon injuries (n = 1), management of elbow epicondylitis (n = 2), management of patellar tendinopathy (n = 1) and complications related to BMAC (n = 5). Multiple experimental studies investigated the use of BMAC for tendon repair; nonetheless, there are only limited clinical studies available in this field. Unfortunately, due to the scarcity of studies, which were mainly case series, the current level of evidence is weak. We strongly recommend further future randomised controlled studies in this field to allow scientists and clinicians make evidence-based conclusions.

To systematically review the available preclinical evidence of adult stem cells as a biological augmentation in the treatment of animal anterior cruciate ligament (ACL) injury.

Cervical cancer is the fourth most common cancer affecting women worldwide. Among many factors, the presence of cancer stem cells, a subpopulation of cells inside the tumor, has been associated with a worse prognosis. Considering the importance of gene expression studies to understand the biology of cervical cancer stem cells (CCSC), this work identifies stable reference genes for cervical cancer cell lines SiHa, HeLa, and ME180 as well as their respective cancer stem-like cells. A literature review was performed to identify validated reference genes currently used to normalize RT-qPCR data in cervical cancer cell lines. Then, cell lines were cultured in regular monolayer or in a condition that favors tumor sphere formation. RT-qPCR was performed using five reference genes: ACTB, B2M, GAPDH, HPRT1, and TBP. Stability was assessed to validate the selected genes as suitable reference genes. The evaluation validated B2M, GAPDH, HPRT1, and TBP in these experimental conditions. Among them, GAPDH and TBP presented the lowest variability according to the analysis by Normfinder, Bestkeeper, and ΔCq methods, being therefore the most adequate genes to normalize the combination of all samples. These results suggest that B2M, GAPDH, HPRT1, and TBP are suitable reference genes to normalize RT-qPCR data of established cervical cancer cell lines SiHa, HeLa, and ME180 as well as their derived cancer stem-like cells. Indeed, GAPDH and TBP seem to be the most convenient choices for studying gene expression in these cells in monolayers or spheres.

Filgrastim (NEUPOGEN®) is the originator recombinant human granulocyte colony-stimulating factor widely used for preventing neutropenia-related infections and mobilizing hematopoietic stem cells. This report presents findings of a systematic literature review and meta-analysis of efficacy and safety of originator filgrastim to update previous reports.

Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways.

This review summarizes the reported molecular mechanisms underlying the antileukemic property of Sesquiterpene Lactones (SLs). This systematic review was registered in the PROSPERO database and conducted following the PRISMA Statements. The MeSH terms, Sesquiterpenes, Lactones and Leukemia were used in four databases (Pubmed, Web of Science, Scopus and Bireme). There were 281 studies selected, but after exclusions, due to replication (n = 172) or not following PECOS criteria (n = 24), 148 studies remained. Of the 148 articles, only 22 were submitted to quality assessment and were scored in high level if more than two techniques, to elucidate antileukemic properties, were described, and then data were extracted. The studies mostly used human leukemia cell lines including primary and established cells, with or without chemotherapy resistance. The SLs used were obtained principally from plants. The antileukemic properties of SLs were extracted from 22 high level studies. They included cell death induction, mainly by apoptosis, as well as cell differentiation, cell cycle disruption, leukemia cancer stem cell growth inhibition and NF-κB pathway inhibition; the latter is a promising therapeutic target for lymphoid malignancies. We concluded that, in spite of the necessity of better toxicological profile characterization of SLs, the antileukemic properties of these compounds support the proposal that the SLs are promising candidates for the treatment of leukemia.

The incidence of knee ligament injury is increasing and represents a significant cost to healthcare providers. Current interventions include tissue grafts, suture repair and non-surgical management. These techniques have demonstrated good patient outcomes but have been associated graft rejection, infection, long term immobilization and reduced joint function. The limitations of traditional management strategies have prompted research into tissue engineering of knee ligaments.

Fracture non-union is a significant problem with a wide range demographic and massive socioeconomic elements, as well as the clinical difficulties it presents. Conventional treatments with autograft and allograft bone grafting pose serious difficulties, thus, it is necessary to develop novel techniques with our ever increasing knowledge of bioengineering using natural materials.

Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have significant risks, making them infeasible and difficult in many cases. Mesenchymal stem cells (MSCs) can be applied to joints and may regenerate the cartilage damaged in OA, this therapy may be advantageous to existing treatments.

The purpose of this article was to perform a systematic review of the recent literature on urethral tissue engineering. A total of 31 articles describing the use of tissue engineering for urethra reconstruction were included. The obtained results were discussed in three groups: cells, scaffolds, and clinical results of urethral reconstructions using these components. Stem cells of different origin were used in many experimental studies, but only autologous urothelial cells, fibroblasts, and keratinocytes were applied in clinical trials. Natural and synthetic scaffolds were studied in the context of urethral tissue engineering. The main advantage of synthetic ones is the fact that they can be obtained in unlimited amount and modified by different techniques, but scaffolds of natural origin normally contain chemical groups and bioactive proteins which increase the cell attachment and may promote the cell proliferation and differentiation. The most promising are smart scaffolds delivering different bioactive molecules or those that can be tubularized. In two clinical trials, only onlay-fashioned transplants were used for urethral reconstruction. However, the very promising results were obtained from animal studies where tubularized scaffolds, both non-seeded and cell-seeded, were applied. Impact statement The main goal of this article was to perform a systematic review of the recent literature on urethral tissue engineering. It summarizes the most recent information about cells, seeded or non-seeded scaffolds and clinical application with respect to regeneration of urethra.

Tissue engineering is now being used in Achilles tendon (AT) repair in animal models. There are many preclinical studies that have used different types of stem cells for AT repair. However, there are no systematic reviews that evaluate all these studies to see which type of stem cell provides the most improvement for AT repair in animal models. Sahni V et al.,(1) divided the multiple stem cell types into three broad categories; Tendon derived stem cells (TDSCs), mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs). These three categories have been used in this systematic review to group the different stem cell types together and to also see which category of stem cells provide superior enhancement of AT repair.

Spinal surgery presents a challenge for both neurosurgery and orthopaedic surgery. Due to the heterogeneous differentiation potential of mesenchymal stem cells, there is much interest in the treatment of spine surgery. Animal and human trials focussing on the efficacy of mesenchymal stem cells in spinal cord injury, spine fusion and disc degeneration were included in this systematic review. Published articles up to January 2016 from MEDLINE, PubMed and Ovid were used by searching for specific terms. Of the 2595 articles found, 53 met the selection criteria and were included for analysis (16 on spinal cord injury, 28 on intervertebral disc repair and 9 on spinal fusion). Numerous studies reported better results when the mesenchymal stem cells were used in co-culture with other cells or used in scaffolds. Mesenchymal stem cells were also found to have an immune-modulatory role, which can improve surgical outcome. This systematic review suggests that mesenchymal stem cells can be used safely and effectively for these spinal surgery treatments. Whilst, in certain studies, mesenchymal stem cells did not necessarily show improved results from existing treatments, they provide an alternative option. This can reduce morbidity that arises from current surgical treatment.

The objective of the study is to compare outcomes of ultrasound-guided aspiration of fetal ovarian cysts with conservative management.

Systematic review.

In recent years, the mesenchymal stem cells (MSCs) have provided the new opportunities to treat different disorders including infertility. Different studies have suggested that the MSCs have ability to differentiate into germ-like cells under specific induction conditions as well as transplantation to gonadal tissues. The aim of this systematic review was to evaluate the results obtained from different studies on MSCs therapy for promoting fertility. This search was done in PubMed and Science Direct databases using key words MSCs, infertility, therapy, germ cell, azoospermia, ovarian failure and mesenchymal stem cell. Among the more than 11,400 papers, 53 studies were considered eligible for more evaluations. The obtained results indicated that the most studies were performed on MSCs derived from bone marrow and umbilical cord as compared with the other types of MSCs. Different evaluations on animal models as well as in vitro studies supported from their role in the recovery of spermatogenesis and folliculogenesis. Although the data obtained from this systematic review are promising, but the further studies need to assess the efficiency and safety of transplantation of these cells in fertility recovery.

Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumours mainly develop in the adrenal medullary tissue, with an abdominal mass as the most common presentation. About 50% of patients have metastatic disease at diagnosis. The high-risk group is characterised by metastasis and other features that increase the risk of an adverse outcome. High-risk patients have a five-year event-free survival of less than 50%. Retinoic acid has been shown to inhibit growth of human neuroblastoma cells and has been considered as a potential candidate for improving the outcome of patients with high-risk neuroblastoma. This review is an update of a previously published Cochrane Review.

This study aims to systematically evaluate the efficacy and safety of core decompression combined transplantation of autologous bone marrow stem cells (CDBMSCs) for treatment of avascular necrosis of the femoral head (ANFH).

Traditional attempts to grow bone grafts in vitro have been based on culturing cell-scaffold constructs under static culture conditions. However, limitations associated with this approach have led to the development of various types of technologies and equipments. One of these is a bioreactor acting as an intermediate between static (in vitro) and dynamic (in vivo) conditions, which can mimic physiological and mechanical body conditions.

Fracture healing encompasses a succession of dynamic multifactorial metabolic events, which ultimately re-establishes the integrity of the biomechanical properties of the bone. Up to 10% of the fractures occurring annually will need additional surgical procedures because of impaired healing. The aim of this article is to review the current literature regarding the use of bone marrow aspirate concentrate (BMAC) and its effectiveness in the management of bone defects.