Bone marrow-derived mononuclear cells (BMMNCs) offer the promise of augmenting poststroke recovery. There is mounting evidence of safety and efficacy of BMMNCs from preclinical studies of ischemic stroke; however, their pooled effects have not been described.

Since the discovery and isolation of a mesenchymal stem cell population from within the stromal vascular fraction (SVF) of adipose tissue, there has been a concerted effort to discover the characteristics of these cells. Particular attention has been paid to their morphology, selfrenewal capacity, multi-lineage differentiation capabilities and, as is of greatest interest in this instance, their cell surface profile.

Mesenchymal stem cells (MSC) are unique in their ability to self-renew and differentiate into one of many lineage possibilities. It is therefore integral to preserve these qualities to prevent the far reaching effects of a defective stem cell. Human mesenchymal stem cells (hMSC) are precursors for and can differentiate into osteoblasts, adipocytes and chondrocytes. They were originally found in the bone marrow, but have also been located in the umbilical cord, adipose tissue and muscle. Few studies have been conducted into the in vivo effects of age on these cells. This contribution reviews current knowledge surrounding the effects of age on the characteriation and differentiation of human mesenchymal stem cells.

To provide a comprehensive overview of the basic science rationale, surgical technique, and clinical outcomes of 1-step cartilage repair technique used as a treatment strategy for cartilage defects.

Despite recent advances in the treatment of arthritis with the development of disease-modifying antirheumatic drugs, 30% of patients still fail to respond to treatment. Given the potent anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSC) and their ability to repair damaged cartilage, bone, and tendons, it has been proposed that MSC could be ideal for cell-based treatment of arthritis.

CD133-positive melanoma cells are thought to be melanoma-initiating cells with cancer stem cell (CSC) characteristics. Some researchers have reported that CD133-negative subsets can also initiate tumors, so the clinical significance of a CD133-positive subpopulation of cells in melanoma remains controversial. This systematic review was designed to assess the value of CD133 as a CSC marker in melanomas. A meta-analysis was also performed to cumulatively analyze the data on CD133 expression levels in the selected studies.

Development of innovative therapies in intensive care medicine is particularly important since diseases as sepsis, acute respiratory distress syndrome (ARDS) and acute renal injury (AKI) have an elevated morbidity and mortality in spite of current gold-standard approaches. Mesenchymal stem cells (MSC) may have a promising role due to their properties in immunomodulation, tissue reparation and microbial clearance. Preclinical data and results of a systematic review of PubMed, PMC and ClinicalTrials.gov have been included to review the role of MSC therapy in sepsis, ARDS and AKI. A description of MSC biology, sources and benefits in preclinical models was included. A phase I/II clinical trial (RCT) is recruiting neutropenic patients with septic shock. In ARDS, the START trial (Stem cells in ARDS Treatment) is a phase I/II study of bone marrow-derived human MSC (hMSC) that is currently recruiting patients. In AKI, a phase I study has demonstrated the safety of hMSCs infusion in patients undergoing cardiac surgery with high risk to develop AKI. A phase II study is still active. The results of these studies will determine the real feasibility of MSC therapy in critically ill patients.

The emerging of intracavernosal injection (ICI) of vasoactive materials was a major breakthrough in the treatment of erectile dysfunction (ED). However, the current state and future direction of ICI role in the armamentarium of diagnosis, prevention and treatment of ED are not well defined. The aim of this study was to address the current place of ICI in the armamentarium of ED diagnosis and treatment. An English-language MEDLINE review for the utilization of 'intracavernosal injection & erectile dysfunction' was performed from 1990 to present time. Four hundred forty-eight articles were analyzed and classified according to the current utilization of ICI in the following conditions; diagnosis of ED, phosphodiesterase-5 inhibitor (PDE5I) non-responders, diabetes, post radical prostatectomy (RP), stem cells and gene therapy, new intracavernosal drugs, adverse effects and couple satisfaction. This paper is not a standard systematic review; it is eventually a literature review of original peer-reviewed manuscripts and clinical trials reported in Medline. The comprehensive analyses of all the reviewed data were not possible as the level of evidence for utility of ICI in each topic was not available. Current date have established the role of ICI of vasoactive materials as a very common alternative domain in treatment of severe ED particularly in diabetic patients, post-RP, PDE5I non-responders. Further, new studies have denoted the potential future role of intracavernosal treatment for ED in the era of stem cells and gene therapy. ICI of vasoactive material continues to be a highly effective and safe treatment tool for men with wide varieties of ED etiologies. Several experimental and clinical studies are currently investigating new ICI materials. Hopefully in the near future, we might witness evolved molecules and innovative strategies that could help to treat ED patients with different etiologies.

Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and limitations for a clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in clinical settings, in order to summarize the current evidence of their efficacy for the treatment of cartilage lesions and OA.Among the 60 selected studies, 7 were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the two different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC versus PBSCs. Overall, despite the increasing literature on this topic, the evidence is still limited, in particular for high-level studies. On the other hand, the available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell source, indication, or administration method. This effectiveness has been reflected by clinical improvements and also positive MRI and macroscopic findings, whereas histologic features gave more controversial results among different studies. Third, young age, lower BMI, smaller lesion size for focal lesions, and earlier stages of OA joints have been shown to correlate with better outcomes, even though the available data strength does not allow to define clear cutoff values. Finally, definite trends can be observed with regard to the delivery method: currently cultured cells are mostly being administered by i.a. injection, while one-step surgical implantation is preferred for cell concentrates. In conclusion, while promising results have been shown, the potential of these treatments should be confirmed by reliable clinical data through double-blind, controlled, prospective and multicenter studies with longer follow-up, and specific studies should be designed to identify the best cell sources, manipulation, and delivery techniques, as well as pathology and disease phase indications.

Late graft failure after allogeneic haematopoietic cell transplantation (HCT) can result from the failed engraftment of long-term engrafting cells. The use of thrombopoietin (TPO) receptor agonists (TRA) has been extensively studied and remains an important component of experimental ex vivo stem cell expansion protocols, but its use in allogeneic transplantation is still evolving.

We systematically reviewed published preclinical studies to evaluate the effectiveness of cell-seeded tissue engineering approach for urethral reconstruction in an animal model. The outcomes were summarized by success factors in the animal experiments, which evaluate the possibility and feasibility of a clinical application in the future. Preclinical studies of tissue engineering approaches for urethral reconstruction were identified through a systematic search in PubMed, Embase, and Biosis Previews (web of science SP) databases for studies published from 1 January 1980 to 23 November 2014. Primary studies were included if urethral reconstruction was performed using a tissue-engineered biomaterial in any animal species (with the experiment group being a cell-seeded scaffold and the control group being a cell-free scaffold) with histology and urethrography as the outcome measure. A total of 15 preclinical studies were included in our meta-analysis. The histology and urethrography outcome between the experimental and control groups were considered to be the most clinically relevant. Through this systematic approach, our outcomes suggested that applying the cell-seeded biomaterial in creating a neo-urethra was stable and effective. And multi-type cells including epithelial cells as well as smooth muscle cells or fibroblasts seemed to be a better strategy. Stem cells, especially after epithelial differentiation, could be a promising choice for future researches.

The aim of this study was to systematically present the best available stem cell therapies for children with cerebral palsy (CP). The databases Medline, PubMed, EMBASE, and the Cochrane Controlled Trials Register for RCTs were searched for studies published from 1967 to August 2015. Systematic reviews, randomised controlled trials (RCTs), controlled trials, uncontrolled trials, cohort studies, open-label studies, and a meta-analysis were analysed. Of 360 articles, seven fulfilled the inclusion criteria: one RCT and six were open-label trials. In these studies, one application of stem cells for children with CP was typical, and the total number of cells administered to patients ranged from 10(6) to 10(8)/kg. Different routes of cell delivery were used, though in most studies motor development was applied as an indicator of primary outcomes. In three articles, neuroimaging studies were also implemented to confirm the efficacy of the therapies. Observation periods varied from 3months to 5years, and patients' tolerance of the therapy was generally good. Stem cell therapy may improve some symptoms in patients with CP, though larger studies are needed to examine the impact of stem cell therapy upon CP.

Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Thus, sorafenib is being proposed for use in MM.

In 2007 the ACPGBI published a position statement on the management of cryptoglandular fistula in ano. Over the last seven years a number of new treatments have been developed and the aim of this systematic review was to assess their effectiveness.

Primary studies in animal models and humans have suggested the therapeutic potential of autologous stem cell for treating chronic lower extremity ulcers. However, the results of pilot randomized controlled trials (RCTs) in humans have been inconsistent. A meta-analysis of RCTs was performed to evaluate the role of autologous stem cell-based therapy for lower extremity ulcers.Studies were identified during a systematic search of Medline, Embase, Cochrane's library, and references cited in related reviews and studies. Studies were included if they were RCTs published in English, recruited patients with lower extremity ulcers who were assigned to either a group for the topical therapy with autologous stem cells, and reported data regarding the healing of the ulcers.Relative risks (RRs) for healing rate and standardized mean differences (SMDs) for the changes in the mean sizes of ulcers were evaluated with a random-effects model. Overall, autologous stem cell-based therapy was associated with better healing of lower extremity ulcers (12 comparisons, 290 patients, RR for partial healing = 3.07, 95% confidence interval [CI] = 1.14-8.24, P = 0.03; RR for complete healing = 2.26, 95% CI = 1.48-3.16, P < 0.001) with little heterogeneity (I = 0%). Moreover, autologous stem cell-based therapy was associated with a greater reduction in mean ulcer size (SMD = -0.63, 95% CI = -1.03 to -0.22, P = 0.002). Subgroup analyses indicated that stem cells from peripheral blood and bone marrow seemed to exert similar beneficial effects on the healing of ulcers. Stem cell therapy was not associated with any increased risks for adverse events. The optimized sources, amounts, and delivery methods of stem cell -based therapy for patients with chronic lower extremity ulcers need to be determined, and the long-term effects of stem cell-based therapy on clinical outcomes need further exploration.Autologous stem cell-based therapy is effective and safe for improving the healing of chronic lower extremity ulcers and large-scale RCTs are needed to confirm our findings.

Knee osteoarthritis (OA) is a debilitating condition that may ultimately require total knee arthroplasty (TKA). Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI). The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment.

A systematic review and single-arm meta-analysis of clinical trials.

Avascular necrosis of the femoral head is caused by a multitude of etiologic factors and is associated with collapse with a risk of hip arthroplasty in younger populations. A focus on early disease management with the use of stem cells was proposed as early as 1985 by the senior author (PH). We undertook a systematic review of the medical literature to examine the progress in cell therapy during the last 30 years for the treatment of early stage osteonecrosis.

Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone for the long-term treatment of bipolar disorder. A number of biological properties of lithium have been discovered, including its hematological, antiviral and neuroprotective effects. In this article, a systematic review of the effect of lithium on hematopoietic, mesenchymal and neural stem cells is presented. The beneficial effects of lithium on the level of hematopoietic stem cells (HSC) and growth factors have been reported since 1970s. Lithium improves homing of stem cells, the ability to form colonies and HSC self-renewal. Lithium also exerts a favorable influence on the proliferation and maintenance of mesenchymal stem cells (MSC). Studies on the effect of lithium on neurogenesis have indicated an increased proliferation of progenitor cells in the dentate gyrus of the hippocampus and enhanced mitotic activity of Schwann cells. This may be connected with the neuroprotective and neurotrophic effects of lithium, reflected in an improvement in synaptic plasticity promoting cell survival and inhibiting apoptosis. In clinical studies, lithium treatment increases cerebral gray matter, mainly in the frontal lobes, hippocampus and amygdala. Recent findings also suggest that lithium may reduce the risk of dementia and exert a beneficial effect in neurodegenerative diseases. The most important mediators and signaling pathways of lithium action are the glycogen synthase kinase-3 and Wnt/β-catenin pathways. Recently, to study of bipolar disorder pathogenesis and the mechanism of lithium action, the induced pluripotent stem cells (iPSC) obtained from bipolar patients have been used.

Despite the vast improvements of cell therapy in spinal cord injury treatment, no optimum protocol has been developed for application of neural stem/progenitor cells. In this regard, the present meta-analysis showed that the efficacy of the neural stem/progenitor cell (NSPC) transplantation depends mainly on injury model, intervention phase, transplanted cell count, immunosuppressive use, and probably stem cell source. Improved functional recovery post NSPC transplantation was found to be higher in transection and contusion models. Moreover, NSPC transplantation in acute phase of spinal injury was found to have better functional recovery. Higher doses (>3×10(6)cell/kg) were also shown to be optimum for transplantation, but immunosuppressive agent administration negatively affected the motor function recovery. Scaffold use in NSPC transplantation could also effectively raise functional recovery.