Despite significant advances in the treatment of Crohn's disease (CD), most patients still develop stricturing or penetrating complications that require surgical resections. We performed a systematic review of mechanisms and potential treatments for tissue damage lesions in CD patients.

γδ T cells are a subpopulation of lymphocytes expressing heterodimeric T-cell receptors composed of γ and δ chains. They are morphologically and functionally heterogeneous, innate yet also adaptive in behavior, and exhibit diverse activities spanning immunosurveillance, immunomodulation, and direct cytotoxicity. The specific responses of γδ T cells to allografts are yet to be fully elucidated with evidence of both detrimental and tolerogenic roles in different settings. Here we present an overview of γδ T-cell literature, consider ways in which their functional heterogeneity contributes to the outcomes after transplantation, and reflect on methods to harness their beneficial properties.

Tendons and ligaments are connective tissues that have been comparatively less studied than muscle and cartilage/bone, even though they are crucial for proper function of the musculoskeletal system. In tendon biology, considerable progress has been made in identifying tendon-specific genes (Scleraxis, Mohawk, and Tenomodulin) in the past decade. However, besides tendon function and the knowledge of a small number of important players in tendon biology, neither the ontogeny of the tenogenic lineage nor signaling cascades have been fully understood. This results in major drawbacks in treatment and repair options following tendon degeneration. In this review, we have systematically evaluated publications describing tendon-related genes, which were studied in depth and characterized by using knockout technologies and the subsequently generated transgenic mouse models (Tg) (knockout mice, KO). We report in a tabular manner, that from a total of 24 tendon-related genes, in 22 of the respective knockout mouse models, phenotypic changes were detected. Additionally, in some of the models it was described at which developmental stages these changes appeared and progressed. To summarize, only loss of Scleraxis and TGFβ signaling led to severe tendon developmental phenotypes, while mice deficient for various proteoglycans, Mohawk, EGR1 and 2, and Tenomodulin presented mild phenotypes. These data suggest that the tendon developmental system is well organized, orchestrated, and backed up; this is even more evident among the members of the proteoglycan family, where the compensatory effects are much clearer. In future, it will be of great importance to discover additional master tendon transcription factors and the genes that play crucial roles in tendon development. This would improve our understanding of the genetic makeup of tendons, and will increase the chances of generating tendon-specific drugs to advance overall treatment strategies.

The prevalence of sexual dysfunctions has increased over the last decades; despite a number of available treatments for erectile dysfunction (ED), premature ejaculation (PE), and Peyronie's disease (PD), still several unmet therapeutic needs deserve to be fulfilled. The aim of this review is to detail on phase I and II clinical trials investigating novel medical treatments for ED, PE, and PD.

The purpose of the present study was to see if there is a correlation between the effect of interferons in crevicular fluid and periodontitis, evaluating literature. Interferon gamma (IFN-γ) is an immunoregulatory cytokine that, when activated by its receptor, plays an important role in the activation of inflammatory processes, which are the basis of periodontal disease. Stem cells in the periodontal ligament, like stem cells from other tissues, have immunomodulatory capacity and are regulated by some cytokines such as interferon-&gamma; (IFN-γ). The study searched MEDLINE databases from 2008 to 2018. Clinical human in vitro and in vivo studies had reported a correlation between interferon and periodontitis. The initial search obtained 359 citations. After screening and determination of eligibility, nine articles were included in the review. Significant (p < 0.05) increases in IFN-γ gene expression were observed in some studies in the chronic periodontitis group. In some cases it was suggested that molecular mechanisms underlie the possible roles of IFN-γ in the inhibition of osteoclastogenesis. Neopterin belongs to the chemical group known as pteridines. It is synthesised by human macrophages upon stimulation with the interferon-gamma. Neopterin concentrations in body fluids are high in the case of infections, immune diseases or graft rejection. In the chronic periodontitis group, this marker is significantly higher. These studies underlined the clinical evidence between interferons in the crevicular fluid and inflammatory response of periodontitis. However, there is a lack of scientific evidence that could lead the clinician to an interferon-modulated therapy because of periodontitis.

Spinal cord injury (SCI) has long been a subject of great interest in a wide range of scientific fields. Several attempts have been made to demonstrate motor function improvement in rats with SCI after transplantation of induced pluripotent stem cells (iPSC). This systematic review and meta-analysis was designed to summarize the effects of iPSC on locomotor recovery in rat models of SCI.

Anal fistula occurs in approximately one in three patients with Crohn's disease and is typically managed through a multimodal approach. The optimal surgical therapy is not yet clear. The aim of this systematic review was to identify and assess the literature on surgical treatments of Crohn's anal fistula.

WHO grade II diffuse low-grade gliomas (DLGGs) were recently divided into sub-groups on the basis of their molecular profiles. IDH wild-type (IDH-wt) tumors seem to be associated with unfavorable prognoses due to biological similarities to glioblastomas. The authors performed a systematic review and meta-analysis of literature examining epidemiology, clinical characteristics, management, and the outcome of IDH-wt grade II DLGGs. According to PRISMA guidelines, a comprehensive review of studies published from January 2009 to October 2017 was carried out. The authors identified series that examined the prevalence rate, clinical and radiological characteristics, treatment, and outcome of IDH-wt DLGGs. Variables influencing outcomes were analyzed using a random-effects meta-analysis model. Finally, a meta-regression analysis was performed to examine the impact of therapeutic strategies on the effect-size. Twenty-two studies were included in this systematic review. The IDH-wt prevalence rate was 22.9% (95% CI 18.4-27.4%). The hazard ratio for this molecular subgroup in the DLGGs population was 3.46 (95% CI 2.24-5.36; p < 0.001), and the heterogeneity was significant (I2 = 85%, τ2 = 0.88) (HR range 1.28-376). Nonetheless, publication bias did not affect the analysis (p = 0.176). The meta-regression revealed that the extent of resection and post-operative chemotherapy affected the outcome in the IDH-wt subgroup (p < 0.001 and 0.015, respectively), with no significant association of the HR with the rate of RT or RT + CHT. The prevalence of IDH-wt tumors is approximately 23% of DLGGs. The absence of IDH mutation is associated with a heterogeneous outcome, and its therapeutic relevance for postoperative management remains unclear. Maximal surgical resection improves the overall survival in the DLGGs population, beyond molecular status. Further molecular stratification is needed to better understand IDH-wt behavior and therapeutic response.

To reveal the particular aspects of the tumor microenvironment of malignant melanomas, a systematic review including 34 representative papers was performed. The review took into account the aspects related the Wnt/β-catenin pathway-related epithelial-mesenchymal transition (EMT) versus mesenchymal-epithelial transition (MET) of keratinocytes, fibroblasts and melanoma cells, as possible tools for understanding genesis and evolution of malignant melanoma. The possible reversible features of EMT and the role of tumor microenvironment in the metastatic process were also analyzed. A particular issue was related on the cancer stem cells that include melanocyte stem cells (McSCs) and multipotent mesenchymal stem/stromal cells (MSCs). As the McSCs embryological development in mouse is not similar to human development, the role of stem cells in genesis and development of human melanoma should be proved in human melanoma cells only. For further development of targeted therapy, a better understanding of melanomagenesis pathways and its microenvironment particularities is necessary.

Intra-articular (IA) injections are commonly used to treat knee arthritis pain; however, whether their efficacy generalizes to ankle arthritis remains debatable. We aimed to evaluate the evidence for IA therapies in the management of this patient population.

Previous studies have demonstrated that intramyocardial human CD34+ cells may relieve symptoms and improve clinical outcomes in chronic refractory angina unresponsive to optimal medical therapy or not amenable to revascularization.

Adipose tissue has classically functioned as a filler in restoring facial volume. Adipose tissue is also rich in stem cells, which may have a role in regenerative medicine.

Alzheimer's disease (AD) is a globally prevalent neurodegenerative disease, clinically characterized by progressive memory loss and gradual impairment of cognitive functions. Mesenchymal stem cells (MSCs) transplantation has been considered a possible therapeutic method for Alzheimer's disease (AD). However, no quantitative data synthesis of MSC therapy for AD exists. We conducted a systematic review and meta-analysis to study the effects of MSCs on cognitive deficits in animal models of AD.

Steroid (glucocorticoid)-induced osteonecrosis of the femoral head (SONFH) is a metabolic disease that occurs due to the use of glucocorticoid drugs, leading to impaired blood supply to the femoral head and death of bone cells and bone marrow composition, which in turn lead to structural change, collapse of the femoral head, and articular dysfunction. SONFH is a challenging disorder to treat in adults due to frequent collapse of the femoral head and dysfunction of the hip joint. Eventually, patients require joint arthroplasty surgery, which severely impairs the patients' quality of life. However, the exactly pathogenesis of SONFH is still not clear. Recently, as the development of precision medicine and lucubrating on stem cell and molecular biology, the exact pathogenesis of SONFH is being investigated and more new treatments are being explored. This review article discusses five major theories about the pathogenesis of SONFH.

Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy.

Morgagni diaphragmatic hernia (MH) is rare. We report our experience based on routine patch use in MH repair to curb recurrence. A systematic review and meta-analysis were performed to study the recurrence and complications associated with minimally invasive surgery and the use of patch.

Obesity is an increasing global health problem, but its treatment is not yet optimal, especially in the long term. For this reason, preclinical studies have been conducted relating to a new therapeutic strategy for obesity based on adipose-derived mesenchymal stem cells (AD-MSCs). The aim of our systematic review is to summarize these findings deriving from the animal model in order to establish whether there is sufficient evidence to justify going forward to clinical studies.

Chronic ulcers remain a difficult challenge in healthcare systems. While treatment options are limited, stem cells may be a novel alternative. Adipose-derived stem cells (ADSC) have become increasingly popular compared with bone marrow-derived stem cells as they are far easier to harvest. To summarize the current status of treating chronic ulcers with ADSC, this systematic review includes all clinical trials on the subject from PubMed and EmBase, as well as all registered clinical trials on ClinicalTrials.Gov. A total of nine clinical trials and fourteen registered trials were included. The studies were significantly different in terms of study design and patient population, and the overall quality of the studies was low to moderate. Despite the overall low study quality and the significant differences between the studies, some conclusions were consistent: ADSCs are safe, improve the healing of chronic ulcers, and reduce pain. As these results are consistent despite the shortcomings of the studies, they appear to highlight the efficacy of ADSCs in the treatment of chronic ulcers. Larger numbers of higher quality studies are needed to determine the precise role of ADSCs in treating chronic leg ulcers.

It is now well established that regenerative medicine and stem cell therapy are the most promising approach to obtain full tissue regeneration by using various cell types including stem cells isolated from adult tissues, embryonic stem cells, and induced pluripotent stem cells (iPSCs). Recently, iPSCs have been successfully differentiated into osteoprogenitors to facilitate repair and regeneration of bone defects. Thus, the purpose of this systematic review and meta-analysis is to summarize the articles published that assess the osteogenic potential of iPSCs in vitro and their ability to heal bone defects in reconstructive surgery. PICO questions were subjected to literature search in four different databases. Methodological and risk of bias assessment of the included in vitro and in vivo articles were performed. Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of evidence for each outcome variable included in the systematic review. In vivo bone formation was selected as the primary outcome for meta-analysis, and publication bias was explored using funnel plots. Initial literature search retrieved 4,772 studies, whereas only 70 articles included in the review. Yamanaka set was the commonly used reprogramming factor introduced with different vectors into the somatic cells. Several somatic cell sources have been used to successfully produce the iPSCs. iPSCs have osteogenic differentiation capacities and would be considered as a new source of stem cells that can be used in reconstructive surgery for bone regeneration.

The objective of this Review is to describe the safety and efficacy of adipose stem/stromal cells (ASC) and stromal vascular fraction (SVF) in treating common diseases and the next steps in research that must occur prior to clinical use. Pubmed, Ovid Medline, Embase, Web of Science, and the Cochrane Library were searched for articles about use of SVF or ASC for disease therapy published between 2012 and 2017. One meta-analysis, 2 randomized controlled trials, and 16 case series were included, representing 844 human patients. Sixty-nine studies were performed in preclinical models of disease. ASCs improved symptoms, fistula healing, remission, and recurrence rates in severe cases of inflammatory bowel disease. In osteoarthritis, ASC and SVF improved symptom-related, functional, radiographic, and histological scores. ASC and SVF were also shown to improve clinical outcomes in ischemic stroke, multiple sclerosis, myocardial ischemia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, chronic liver failure, glioblastoma, acute kidney injury, and chronic skin wounds. These effects were primarily paracrine in nature and mediated through reduction of inflammation and promotion of tissue repair. In the majority of human studies, autologous ASC and SVF from liposuction procedures were used, minimizing the risk to recipients. Very few serious, treatment-related adverse events were reported. The main adverse event was postprocedural pain. SVF and ASC are promising therapies for a variety of human diseases, particularly for patients with severe cases refractory to current medical treatments. Further randomized controlled trials must be performed to elaborate potential safety and efficacy prior to clinical use. Stem Cells 2018;36:1311-1328.