Background: One of the greatest challenges for medicine is to find a safe and effective treatment for immune-related diseases. However, due to the low efficacy of the treatment available and the occurrence of serious adverse effects, many groups are currently searching for alternatives to the traditional therapy. In this regard, the use of human mesenchymal stem cells (hMSCs) represents a great promise for the treatment of a variety of immune-related diseases due to their potent immunomodulatory properties. The main objective of this study is, therefore, to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of the administration of hMSCs for the treatment of immune-related diseases was evaluated. Methods: The article search was conducted in PubMed/MEDLINE, Scopus and Web of Science databases. Original research articles assessing the therapeutic potential of hMSCs administration for the in vivo treatment immune-related diseases, published from 1984 to December 2017, were selected and evaluated. Results: A total of 132 manuscripts formed the basis of this systematic review. Most of the studies analyzed reported positive results after hMSCs administration. Clinical effects commonly observed include an increase in the survival rates and a reduction in the severity and incidence of the immune-related diseases studied. In addition, hMSCs administration resulted in an inhibition in the proliferation and activation of CD19+ B cells, CD4+ Th1 and Th17 cells, CD8+ T cells, NK cells, macrophages, monocytes, and neutrophils. The clonal expansion of both Bregs and Tregs cells, however, was stimulated. Administration of hMSCs also resulted in a reduction in the levels of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-1, IL-2, IL-12, and IL-17 and in an increase in the levels of immunoregulatory cytokines such as IL-4, IL-10, and IL-13. Conclusions: The results obtained in this study open new avenues for the treatment of immune-related diseases through the administration of hMSCs and emphasize the importance of the conduction of further studies in this area.

Mitochondria are small cytosolic organelles and the main source of energy production for the cells, especially in the brain. This organelle has its own genome, the mitochondrial DNA (mtDNA), and genetic variants in this molecule can alter the normal energy metabolism in the brain, contributing to the development of a wide assortment of Neurological Disorders (ND), including neurodevelopmental syndromes, neurodegenerative diseases and neuropsychiatric disorders. These ND are comprised by a heterogeneous group of syndromes and diseases that encompass different cognitive phenotypes and behavioral disorders, such as autism, Asperger's syndrome, pervasive developmental disorder, attention deficit hyperactivity disorder, Huntington disease, Leigh Syndrome and bipolar disorder. In this work we carried out a Systematic Literature Review (SLR) to identify and describe the mitochondrial genetic variants associated with the occurrence of ND. Most of genetic variants found in mtDNA were associated with Single Nucleotide Polimorphisms (SNPs), ~79%, with ~15% corresponding to deletions, ~3% to Copy Number Variations (CNVs), ~2% to insertions and another 1% included mtDNA replication problems and genetic rearrangements. We also found that most of the variants were associated with coding regions of mitochondrial proteins but were also found in regulatory transcripts (tRNA and rRNA) and in the D-Loop replication region of the mtDNA. After analysis of mtDNA deletions and CNV, none of them occur in the D-Loop region. This SLR shows that all transcribed mtDNA molecules have mutations correlated with ND. Finally, we describe that all mtDNA variants found were associated with deterioration of cognitive (dementia) and intellectual functions, learning disabilities, developmental delays, and personality and behavior problems.

Chimeric antigen receptor (CAR) T-cell therapy has shown promise for relapsed/refractory malignancies. Many patients have undergone prior hematopoietic stem cell transplant (HSCT), yet effects of transplant status on CAR T-cell therapy efficacy and safety have not been reported. The purpose of the study is to systematically evaluate the likelihood of achieving optimum response, severe cytokine release syndrome (sCRS), and neurotoxicity in the context of CAR T-cell therapy for HSCT-naïve patients versus those with prior HSCT. Trials were identified in ClinicalTrials.gov, Cochrane Library, and PubMed, and through reference pearl growing. Included studies used CD19-directed CAR T-cells for relapsed/refractory B-lineage Acute Lymphoblastic Leukemia and B cell Chronic Lymphocytic Leukemia, enrolled both HSCT-naïve and prior-HSCT patients, and denoted transplant status with outcomes. Six studies were included for optimum response, five for sCRS incidence, and four for neurotoxicity incidence. The pooled odds ratio for optimum response was 1.57 favoring HSCT-naïve patients (95% CI 0.54-4.61), whereas the pooled odds ratios for sCRS and neurotoxicity were 1.41 (95% CI 0.51-3.94) and 1.37 (95% CI 0.28-6.77), respectively, toward HSCT-naïve patients. Odds ratios were non-statistically significant. Overall risk of bias was moderate. While pooled estimates showed an advantage among HSCT-naïve patients for achieving optimum response and increased likelihood for sCRS and neurotoxicity, findings were not statistically significant. Any differences in efficacy and safety of CAR T-cell therapy cannot be verifiably attributed to transplant status, and additional controlled trials with increased sample sizes are needed to determine whether suggestive patterns favoring HSCT-naïve patients are validated.

Recent studies have investigated the effect of treatments containing adipose-derived mesenchymal stem cells (ADMSCs) on human osteoarthritis. These have mostly used biologic adjuvants which may influence results. Thus, the purpose of this systematic review is to evaluate the current literature on these treatments when used in isolation.

Depression is currently treated by pharmacotherapies that can elicit debilitating side effects for patients. Novel treatment options with limited side effects are currently being researched. Resveratrol is a polyphenol and phytoalexin found in the skins of grapes, red wine, Japanese knotweed, and peanuts. It has been studied extensively for its antioxidant and anti-inflammatory properties. Resveratrol has also gained attention for its neuroprotective properties. The aim of the review was to examine the mechanisms by which resveratrol reduces depressive behaviors in animal models. In total, 22 studies met the established criteria for final review. Behavioral aspects of depression were investigated using validated measures such as the forced swimming test, tail suspension test, sucrose preference test, and open field test. While many physical measures were taken, three main biological mechanisms were explored: Regulation of the hypothalamic⁻pituitary⁻adrenal axis; decreased inflammation; and increased Brain-Derived Neurotrophic Factor and neurogenesis. Based on these findings, resveratrol may be deemed an effective treatment for depression in animal models at doses between 10⁻80 mg/kg/day, although higher doses had the most significant effects. Future studies should examine the effects of resveratrol on depression in humans to determine the eligibility of resveratrol as a natural antidepressant with less severe side effects.

Revascularisation is the gold standard therapy for patients with critical limb ischaemia (CLI). In over 30% of patients who are not suitable for or have failed previous revascularisation therapy (the 'no-option' CLI patients), limb amputation is eventually unavoidable. Preliminary studies have reported encouraging outcomes with autologous cell-based therapy for the treatment of CLI in these 'no-option' patients. However, studies comparing the angiogenic potency and clinical effects of autologous cells derived from different sources have yielded limited data. Data regarding cell doses and routes of administration are also limited.

Cells from the mesenchymal lineage in the dental area, including but not limited to PDL fibroblasts, osteoblasts, and dental stem cells, are exposed to mechanical stress in physiological (e.g., chewing) and nonphysiological/therapeutic (e.g., orthodontic tooth movement) situations. Close and complex interaction of these different cell types results in the physiological and nonphysiological adaptation of these tissues to mechanical stress. Currently, different in vitro loading models are used to investigate the effect of different types of mechanical loading on the stress adaptation of these cell types. We performed a systematic review according to the PRISMA guidelines to identify all studies in the field of dentistry with focus on mechanobiology using in vitro loading models applying uniaxial static compressive force. Only studies reporting on cells from the mesenchymal lineage were considered for inclusion. The results are summarized regarding gene expression in relation to force duration and magnitude, and the most significant signaling pathways they take part in are identified using protein-protein interaction networks.

It is common practice to refer patients to transplantation centers for allogeneic hematopoietic cell transplantation (allo-HCT) for blastic plasmacytoid dendritic-cell neoplasm (BPDCN) despite lack of randomized controlled trials. We performed a systematic review to assess the totality of evidence pertaining to the efficacy of allo-HCT in BPDCN.

The aim of the present systematic review was to offer a timeline of the events taking place during orthodontic tooth movement(OTM).

To overview preclinical animal trials and quantify the effect size that stem cell therapy has on the regeneration of periodontal tissue complex.

With the continued application of fat grafting in plastic surgery, many studies have focused on various factors to improve maintenance of the fat graft volume, such as platelet-rich plasma, adipose-derived stromal/stem cells, and the stromal vascular fraction (SVF). In addition, many review articles have investigated the functions of platelet-rich plasma and adipose-derived stromal/stem cells in fat grafting, although the usefulness of the SVF remains unclear. The aim of the present review was to determine whether SVF use could maintain a fat graft.

Knee joint trauma may result in damage of the intra-articular ligaments, with rupture of the anterior cruciate ligament (ACL) a common and troublesome injury due to poor capabilities for spontaneous regeneration. Autograft and allograft surgical reconstructions are the mainstay of treatment, but have associated risks of failure, therefore tissue-engineering techniques aiming to regenerate the native ACL are being researched as a potential alternative treatment.

Articular cartilage defect remains the most challenging joint disease due to limited intrinsic healing capacity of the cartilage that most often progresses to osteoarthritis. In recent years, stem cell therapy has evolved as therapeutic strategies for articular cartilage regeneration. However, a number of studies have shown that therapeutic efficacy of stem cell transplantation is attributed to multiple secreted factors that modulate the surrounding milieu to evoke reparative processes. This systematic review and meta-analysis aim to evaluate and compare the therapeutic efficacy of stem cell and secretome in articular cartilage regeneration in animal models. We systematically searched the PubMed, CINAHL, Cochrane Library, Ovid Medline and Scopus databases until August 2017 using search terms related to stem cells, cartilage regeneration and animals. A random effect meta-analysis of the included studies was performed to assess the treatment effects on new cartilage formation on an absolute score of 0-100% scale. Subgroup analyses were also performed by sorting studies independently based on similar characteristics. The pooled analysis of 59 studies that utilized stem cells significantly improved new cartilage formation by 25.99% as compared with control. Similarly, the secretome also significantly increased cartilage regeneration by 26.08% in comparison to the control. Subgroup analyses revealed no significant difference in the effect of stem cells in new cartilage formation. However, there was a significant decline in the effect of stem cells in articular cartilage regeneration during long-term follow-up, suggesting that the duration of follow-up is a predictor of new cartilage formation. Secretome has shown a similar effect to stem cells in new cartilage formation. The risk of bias assessment showed poor reporting for most studies thereby limiting the actual risk of bias assessment. The present study suggests that both stem cells and secretome interventions improve cartilage regeneration in animal trials. Graphical abstract ᅟ.

Malignant neoplasms may be composed of several cell groups, including cancer stem cells (CSC). These cells have been related with the capacity of metastasis, relapse and resistance to multiple drugs during chemotherapy. This study aims to identify CSC biomarkers and their expression pattern in human head and neck carcinomas. This study was conducted following the PRISMA checklist. The search for articles was carried out in five databases (PubMed, Scopus, Web of Science, Lilacs and Scielo). The articles found were selected in two phases: 1) reading the titles and / or abstract and 2) reading the full text. At the end, the selected articles were evaluated by QUADAS-2. Most studies evaluated oral neoplastic tissues and, as a control, samples of normal local mucosa. All studies performed immunohistochemistry as a method of immunolocalization and some also applied immunofluorescence. The most commonly used biomarker was CD44. However, other such as Sox2, Oct4, Nestin, Nanog, BMI1, ALDH1, CD133 and CD166 were also found. Several biomarkers were (ALDH1, Sox2, Oct4, ABCB5, AGR2 and TAZ) correlated with clinical characteristics of the tumor, such as staging, tumor size and lymph node metastasis. These data reinforce the CSC theory and favor the use of these biomarkers as possible determinants of prognosis.

For the last two decades, silk has been extensively used as scaffolds in tissue engineering because of its remarkable properties. Unfortunately, the aneural property of cartilage limits its regenerative potential which can be achieved using tissue engineering approach. A lot of research has been published searching for the optimization of silk fibroin (SF) and its blends in order to get the best cartilage mimicking properties. However, according to our best knowledge, there is no systematic review available regarding the use of Bombyx mori derived biomaterials limited to cartilage related studies. This systematic review highlights the in vitro and in vivo work done for the past 7 years on structural and functional properties of B. mori derived biomaterials together with different parameters for cartilage regeneration. PubMed database was searched focusing on in vitro and in vivo studies using the search thread "silk fibroin" and "cartilage". A total of 40 articles met the inclusion criteria. All the articles were deeply studied for cell types, scaffold types and animal models used along with study design and results. Five types of cells were used for in vitro while seven types of cells were used for in vivo studies. Three types of animal models were used for scaffold implantation purpose. Moreover, different types of scaffolds either seeded with cells or supplemented with various factors were explored and discussed in detail. Results suggest the suitability of silk as a better biomaterial because of its cartilage mimicking properties.

Knee osteoarthritis (OA) is one of the preeminent musculoskeletal illnesses in the adult population.

Adipose tissue-derived stem cells (ASCs) in the form of stromal vascular fraction (SVF) and cultured expansion have been applied in clinical settings in some countries to treat osteoarthritis (OA) of knees, one of the most common debilitating, incurable disorders. Since the first report of successful cartilage-like tissue regeneration with autologous adipose SVF containing ASCs, there has been a gradual increase in the number of publications confirming such results. Thus far, most of the reports have been limited to treatments of OA of knees. Recently, successful applications of adipose SVF in treating OA of ankles and hips have been reported. In addition, several groups have reported modified methods of applying adipose SVF, such as combining bone marrow stimulation with adipose SVF or adding additional extracellular matrix (ECM) in treating OA. Here, we present an updated, systematic review of clinical effectiveness and safety in treating OA of knees, ankles, and one hip since 2016 using ASCs in the form of adipose SVF or in cultured expansion, along with a description and suggestion of potential biological mechanisms of cartilage regeneration.

Autoinflammatory diseases (AIDs) are conditions related to defective regulation of the innate immune system. Sanger sequencing of the causative genes has long been the reference for confirming the diagnosis. However, for many patients with a typical AID phenotype, the genetic cause remains unknown. A pioneering study in 2005 demonstrated mosaicism in patients with cryopyrin-associated periodic syndromes (CAPS); the authors found somatic mosaicism in 69% of their cohort of Sanger-negative CAPS patients. We aim to address the extent to which mosaicism contributes to the etiology of AIDs and its impact on phenotype. We retrieved English-language publications reporting mosaicism in AIDs by querying PubMed with no restriction on date and we surveyed French reference centers. We provide a comprehensive clinical and genetic picture of mosaicism in AIDs. We estimate that the proportion of CAPS-like patients presenting mosaicism ranges from 0.5% to 19%. We also discuss the possible links between the proportion of mutated alleles and various clinical features. This review reevaluates the contribution of mosaic DNA variants in CAPS. Mosaicism may be more common than anticipated in other AIDs. No significant difference was demonstrated between variant allele frequency and clinical phenotype. Such knowledge has implications for the development of guidelines for genetic diagnosis, genetic counseling of affected families and effective patient care.

Acute-on-chronic liver failure (ACLF) is a serious life-threatening disease with high prevalence. Liver transplantation is the only efficient clinical treatment for ACLF. Because of the rapid progression and lack of liver donors, it is urgent to find an effective and safe therapeutic approach to ACLF. Recent studies showed that multipotent cell transplantation could improve the patients' liver function and enhance their preoperative condition. Cells such as mesenchymal stem cells, bone marrow mononuclear cells and autologous peripheral blood stem cells, which addressed in this study have all been used in multipotent cell transplantation for liver diseases. However, its clinical efficiency is still debatable. This systematic review and meta-analysis explored the clinical efficiency of multipotent cell transplantation as a therapeutic approach for patients with ACLF. A detailed search of the Cochrane Library, MEDLINE, and Embase databases was conducted from inception to November 2017. The outcome measures were serum albumin, prothrombin time, alanine aminotransferase, total bilirubin, platelets, hemoglobin, white blood cells, and survival time. The quality of evidence was assessed using GRADEpro and Jaded scores. A literature search resulted in 537 citations. Of these, 9 articles met the inclusion criteria. It was found that multipotent cell transplantation was able to alleviate liver damage and improve liver function. Multipotent cell transplantation can also enhance the short-term and medium-term survival rates of ACLF. All 9 research articles included in this analysis reported no statistically significant adverse events, side effects, or complications. In conclusions, this study suggested that multipotent cell transplantation could be recommended as a potential therapeutic supplementary tool in clinical practice. However, clinical trials in large-volume centers still needed.

While the survival rate of children with cancer is increasing, preserving fertility for prepubertal boys is still a challenge. Although intracytoplasmic sperm injection (ICSI) using frozen sperms has revolutionized infertility treatment, it is not applicable for the patients who undergo chemotherapy before puberty since spermatogenesis has not begun. Therefore, preserving spermatogonial stem cells (SSCs) as an experimental option can be provided to prepubertal patients at a risk of damage or loss of their SSCs due to cancer treatments and developmental or genetic disorders. Using frozen SSCs in testicular tissue, successful SSC autotransplantation in mouse and nonhuman primates has shown a promising future for SSC-based cell therapy. Cryopreservation of testicular tissue containing SSCs is the first step to translate SSC-based cell therapy into clinical male infertility treatment, and in the investigation into SSCs, it is very important to evaluate their quantity and functionality during this process. This systematic review summarizes the published data on cryopreservation techniques in human testis tissue for potential utilization in future clinical applications.