Stem cell to be a new intervention for treating intracerebral hemorrhage (ICH) might benefit humans. Therefore, we collected animal studies to find the effect of this innovative treatment. In July 2014, we searched Medline (from 1950), Embase (from 1980), China Biology Medicine disk (from 1978) for studies on stem cells used for treating experimental ICH in animal models that reported neurobehavioral and structural outcome. We evaluated the quality of these studies and used a weighted mean difference random affects model for the meta-analysis. We have collected 30 studies from 650 publications identified through systematic review describing the effects of 5 different type of stem cells on 12 different neurobehavioral scales with 1101 rodents or monkeys. Although there is lack of uniformity of the evaluation methods, these researches showed consistent improvements both in neurobehavioral function and structural outcomes. Besides, the quality of these studies needs to be raised. In conclusion, stem cells hold extensive potential in treating ICH, which should be further evaluated with more evidence-based, high-quality animal studies.

CD133 and Nestin, as the markers of cancer stem cells, have recently been reported frequently in the pathogenesis and development of human gliomas. However, the prognostic role of CD133 and Nestin in gliomas still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and Nestin and the outcome of glioma patients by conducting a systematic review and meta-analysis.

Digestive tract tumors are among the most common and deadliest malignancies worldwide, mainly due to late diagnosis and lack of efficient therapeutics. Current treatments essentially rely on surgery associated with (neo)adjuvant chemotherapy agents. Despite an upfront response, conventional drugs often fail to eliminate highly aggressive clones endowed with chemoresistant properties, which are responsible for tumor recurrence and disease dissemination. Synthetic drugs also present severe adverse systemic effects, hampering the administration of biologically effective dosages. Nanoencapsulation of chemotherapeutic agents within biocompatible polymeric or lipid matrices holds great potential to improve the pharmacokinetics and efficacy of conventional chemotherapy while reducing systemic toxicity. Tagging nanoparticle surfaces with specific ligands for cancer cells, namely monoclonal antibodies or antibody fragments, has provided means to target more aggressive clones, further improving the selectivity and efficacy of nanodelivery vehicles. In fact, over the past twenty years, significant research has translated into a wide array of guided nanoparticles, providing the molecular background for a new generation of intelligent and more effective anti-cancer agents. Attempting to bring awareness among the medical community to emerging targeted nanopharmaceuticals and foster advances in the field, we have conducted a systematic review about this matter. Emphasis was set on ongoing preclinical and clinical trials for liver, colorectal, gastric and pancreatic cancers. To the best of our knowledge this is the first systematic and integrated overview on this field. Using a specific query, 433 abstracts were gathered and narrowed to 47 manuscripts when matched against inclusion/exclusion criteria. All studies showed that active targeting improves the effectiveness of the nanodrugs alone, while lowering its side effects. The main focus has been on hepatocarcinomas, mainly by exploring glycans as homing molecules. Other ligands such as peptides/small proteins and antibodies/antibody fragments, with affinity to either tumor vasculature or tumor cells, have also been widely and successfully applied to guide nanodrugs to gastrointestinal carcinomas. Conversely, few solutions have been presented for pancreatic tumors. To this date only three nanocomplexes have progressed beyond pre-clinical stages: i) PK2, a galactosamine-functionalized polymeric-DOX formulation for hepatocarcinomas; ii) MCC-465, an anti-(myosin heavy chain a) immunoliposome for advanced stage metastatic solid tumors; and iii) MBP-426, a transferrin-liposome-oxaliplatin conjugate, also for advanced stage tumors. Still, none has been approved for clinical use. However, based on the high amount of pre-clinical studies showing enthusiastic results, the number of clinical trials is expected to increase in the near future. A more profound understanding about the molecular nature of chemoresistant clones and cancer stem cell biology will also contribute to boost the field of guided nanopharmacology towards more effective solutions.

Bone marrow stem cells (BMSCs) have been used to treat patient with ST-segment elevation myocardial infarction (STEMI) via intracoronary route. We performed a meta-analysis to evaluate the short-term efficacy and safety of this modality. Seventeen randomized controlled trials (RCTs) of BMSC-based therapy for STEMI, delivered with 9 days of reperfusion and followed up shorter than 12 months, were identified by systematic review. Intracoronary BMSC therapy resulted in an overall significant improvement in left ventricular ejection fraction (LVEF) by 2.74 % (95 % confidence interval (CI) 2.09-3.39, P < 0.00001, I(2) = 84 %) at 3-6-month follow-up and 5.1 % (95 % CI 4.16-6.03, P < 0.00001 and I(2) = 85 %) at 12 months. The left ventricular end-systolic volume (LVESV) and wall motion score index (WMSI) were also reduced at 3-6 months. At 12 months, left ventricular end-diastolic volume (LVEDV), LVESV, and WMSI were significantly reduced in BMSC group. In conclusion, intracoronary BMSC therapy at post-STEMI is safe and effective in patient with acute STEMI.

The purpose of this study was to access the efficacy of mesenchymal stem cells (MSCs) injection in the treatment of knee osteoarthritis (OA).

Various cell types have been assessed for experimental periodontal tissue regeneration in a variety of animal models. Nonetheless, the efficacy of cell-based approaches for periodontal regeneration is still controversial. Therefore, the purpose of this study was to systematically review cell-based approaches for periodontal regeneration in animal studies including a meta-analysis to obtain more clarity on their efficacy. The results of this systematic review and meta-analysis revealed that cell-based approaches have a favorable effect on periodontal tissue regeneration, as displayed by the positive effect of cell-based approaches on new bone, cementum, and periodontal ligament (PDL) formation in periodontal defects. Moreover, subgroup analysis showed a favorable effect on PDL formation by PDL-derived cells, but not by bone marrow mesenchymal stem cells (BMSCs). However, meta-analysis did not show any statistically significant differences in effect between PDL-derived cells and BMSCs. These results provide important information for the implementation of cell-based approaches in clinical practice as a routine treatment for periodontal regeneration in the future.

Aldehyde dehydrogenase 1 (ALDH1) has been identified as a putative cancer stem cell (CSC) marker in lung cancer. However, the clinicopathological and prognostic value of this protein in lung cancer patients remains controversial. Thus, we performed a systematic review and meta-analysis of studies assessing the clinical and prognostic significance of ALDH1 expression in lung cancer.

For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment. A number of animal studies demonstrated beneficial effects of stem/progenitor cell transplantation for pulp-dentin complex regeneration, that is, pulpal tissue, neural, vascular, and dentinal regeneration. We systematically reviewed animal studies investigating stem/progenitor cell-mediated pulp-dentin complex regeneration. Studies quantitatively comparing pulp-dentin complex regeneration after transplantation of stem/progenitor cells versus no stem/progenitor cell transplantation controls in intraoral in vivo teeth animal models were analyzed. The following outcomes were investigated: regenerated pulp area per root canal total area, capillaries per total surface, regenerated dentinal area per total defect area, and nerves per total surface. PubMed and EMBASE were screened for studies published until July 2014. Cross-referencing and hand searching were used to identify further articles. Standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analysis. To assess possible bias, SYRCLE's risk of bias tool for animal studies was used. From 1364 screened articles, five studies (representing 64 animals) were included in the quantitative analysis. Risk of bias of all studies was high. Stem/progenitor cell-transplanted pulps showed significantly larger regenerated pulp area per root canal total area (SMD [95% CI]: 2.28 [0.35-4.21]) and regenerated dentin area per root canal total area (SMD: 6.91 [5.39-8.43]) compared with no stem/progenitor cell transplantation controls. Only one study reported on capillaries per or nerves per total surface and found both significantly increased in stem/progenitor cell-transplanted pulps compared with controls. Stem/progenitor cell transplantation seems to enhance pulp-dentin complex regeneration in animal models. Due to limited data quantity and quality, current evidence levels are insufficient for further conclusions.

To improve osteogenic differentiation and attachment of cells.

Although there is an increase in clinical trials assessing the efficacy of cell therapy in structural and functional regeneration after stroke, there are not enough data in the literature describing the best cell type to be used, the best route, and also the best nanoparticle to analyze these stem cells in vivo. This review analyzed published data on superparamagnetic iron oxide nanoparticle (SPION)-labeled stem cells used for ischemic stroke therapy.

The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data from animal studies can be used to inform clinical trial design. To conduct a systematic review and meta-analysis to (i) systematically review the literatures describing the effect of MSCs therapy in animal models of TBI, (ii) determine the estimated effect size of functional locomotor recovery after experimental TBI, and (iii) to provide empirical evidence of biological factors associated with greater efficacy.

To review the advances and limitations of recent investigations on mandibular distraction osteogenesis (MDO) assisted by mesenchymal stem cell (MSC) transplantation.

Cases of chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) have been reported in hematopoietic stem cells transplantation complicated by graft versus host disease (GVHD). A systematic review of the CIDP-like neuropathies associated with GVHD was conducted until January 2015, analyzing the clinical presentation and the response to different therapeutic regimens. Nineteen patients have been reported in literature including the present one. Fourteen subjects fulfilled the criteria for CIDP, whereas two cases presented with an asymmetric motor onset and one showed motor involvement only associated with anti-ganglioside antibodies. In addition, two subjects already affected by CIDP developed a significant relapse after GVHD. This study reviews the literature data and reports one additional case of CIDP and GVHD, suggesting that the two clinical entities might share a similar immunological background.

Stem cell treatment is a novel therapeutic strategy for erectile dysfunction (ED) patients with bilateral cavernous nerve injury (CNI). The relative animal studies provide important clues to design pre-clinical studies and clinical studies further in the future.

Mesenchymal stem cells (MSC) are widely studied for their immunomodulatory properties. Data from in vitro and pre-clinical models demonstrate that MSC suppress activated immune cells and ameliorate the severity of experimental immune disease. In complex human studies, the immunomodulatory efficacy of MSC therapy is not well established. We conducted a systematic review of clinical studies which used MSC with the purpose of immunomodulation and included at least 10 patients to investigate the efficacy of MSC therapy. Sixty-two studies comprising 10 different immune disorders were included in the analysis, of which 18 studies represented controlled trials. Although several of the studies reported an amelioration of disease severity, other studies failed to observe a beneficial effect of MSC. The low number of randomized controlled trials, small number of studies per disease category and limited immunological readout parameters made it difficult to draw a definitive conclusion on the efficacy of MSC immune therapy.

Management of intervertebral disc (IVD) degenerative disease is challenging, as it is accompanied by irreversible loss of IVD cells. Stem cell transplantation to the disc has shown promise in decelerating or arresting the degenerative process. Multiple pre-clinical animal trials have been conducted, but with conflicting outcomes. To assess the effect of stem cell transplantation, a systematic review and meta-analysis was performed. A comprehensive literature search was conducted through Week 3, 2015. Inclusion criteria consisted of controlled animal trials. Two reviewers screened abstracts and full texts. Disagreements were resolved by a third reviewer. Random effects models were constructed to pool standardized mean difference (SMD). Twenty two studies were included; nine of which were randomized. Statistically significant differences were found with the stem cell group exhibiting increased disc height index (SMD=3.64, 95% confidence interval (CI): 2.49, 4.78; p<0.001), increased MRI T2 signal intensity (SMD=2.28, 95% CI: 1.48, 3.08; p<0.001), increased Type II collagen mRNA expression (SMD=3.68, 95% CI: 1.66, 5.70; p<0.001), and decreased histologic disc degeneration grade (SMD=-2.97, 95% CI: -3.97, -1.97; p<0.001). There was statistical heterogeneity between studies that could not be explained with pre-planned subgroup analyses based on animal species, study designs, and transplanted cell types. Stem cells transplanted to the IVD in quadruped animals decelerate or arrest the IVD degenerative process. Further studies in human clinical trials will be needed to understand if such benefit can be translated to bipedal humans.

The present article summarizes and analyzes the current knowledge about the role of the epithelial to mesenchymal transition (EMT) in the systemic invasiveness of pancreatic cancer.

Ex vivo cultured limbal epithelial transplantation (CLET) with amniotic membrane (AM) as the substrate is a relatively new type of surgical therapy in treating limbal stem cell deficiency (LSCD). We summarize available evidence for determining the efficiency of this technique by a systematic review and meta-analysis.

Low-level laser therapy (LLLT) has been used in several in vitro experiments in order to stimulate cell proliferation. Cells such as fibroblasts, keratinocytes, lymphocytes, and osteoblasts have shown increased proliferation when submitted to laser irradiation, although little is known about the effects of LLLT on stem cells. This study aims to assess, through a systematic literature review, the effects of LLLT on the in vitro proliferation of mesenchymal stem cells. Using six different terms, we conducted an electronic search in PubMed/Medline database for articles published in the last twelve years. From 463 references obtained, only 19 papers met the search criteria and were included in this review. The analysis of the papers showed a concentration of experiments using LLLT on stem cells derived from bone marrow, dental pulp, periodontal ligament, and adipose tissue. Several protocols were used to irradiate the cells, with variations on wavelength, power density, radiation time, and state of light polarization. Most studies demonstrated an increase in the proliferation rate of the irradiated cells. It can be concluded that the laser therapy positively influences the in vitro proliferation of stem cells studied, being necessary to carry out further experiments on other cell types and to uniform the methodological designs.

Obesity is a well recognized risk factor for several types of cancers, many of which occur solely or disproportionately in women. Adipose tissue is a rich source of adipose-derived stem cells (ASC), which have received attention for their role in cancer behavior. The purpose of this systematic review is to present the existing literature on the role of ASCs in the growth, development, progression, and metastasis of cancer, with an emphasis on malignancies that primarily affect women. To accomplish this goal, the bibliographic database PubMed was systematically searched for articles published between 2001 and 2014 that address ASCs' relationship to human cancer. Thirty-seven articles on ASCs' role in human cancer were reviewed. Literature suggests that ASCs exhibit cancer-promoting properties, influence/are influenced by the tumor microenvironment, promote angiogenesis, and may be associated with pathogenic processes through a variety of mechanisms, such as playing a role in hypoxic tumor microenvironment. ASCs appear to be important contributors to tumor behavior, but research in areas specific to women's cancers, specifically endometrial cancer, is scarce. Also, because obesity continues to be a major health concern, it is important to continue research in this area to improve understanding of the impact adiposity has on cancer incidence.