Although many clinical studies have assessed the efficacy of mesenchymal stem cells (MSCs) in knee osteoarthritis, evidence on their efficacy remains unclear owing to heterogeneity of cell entity and concomitant procedures.

Alternative approaches to transplantation for liver failure are needed. One of the alternative approaches is stem cell therapy. However, stem cell therapy in liver failure is not standardized yet, as every centre have their own methods. This systematic review is aimed at compiling and analyzing the various studies that use stem cells to treat liver failure, to get an insight into potential protocols in terms of safety and efficacy by comparing them to controls.

Crohn's disease is a pathological condition that has different options of treatment, but there are patients who need other therapeutic approach, such as the use of adipose-derived mesenchymal stem cells.

Ischemic cardiomyopathy is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ischemic cardiomyopathy. Several stem cell types, including cardiac-derived stem cells, bone marrow-derived stem cells, mesenchymal stem cells, skeletal myoblasts, CD34+ and CD133+ stem cells have been used in clinical trials. Clinical effects mostly depend on transdifferentiation and paracrine factors. One important issue is that a low survival and residential rate of transferred stem cells blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ischemic cardiomyopathy mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical conditions, the particular microenvironment onto which the cells are delivered, and clinical conditions remain to be addressed. Here we provide an overview of modern methods of stem cell delivery, types of stem cells and discuss the current state of their therapeutic potential.

Amyotrophic lateral sclerosis (ALS), which is also known as motor neuron disease (MND), is a fatal disease associated with rapidly progressive disability, for which no definitive treatment exists. Current treatment approaches largely focus on relieving symptoms to improve the quality of life of those affected. The therapeutic potential of cell-based therapies in ALS/MND has not been fully evaluated, given the paucity of high-quality clinical trials. Based on data from preclinical studies, cell-based therapy is a promising treatment for ALS/MND. This review was first published in 2015 when the first clinical trials of cell-based therapies were still in progress. We undertook this update to incorporate evidence now available from randomised controlled trials (RCTs).

The unavailability of sufficient numbers of human primary cells is a major roadblock for in vitro repair of bone and/or cartilage, and for performing disease modelling experiments. Immortalized mesenchymal stromal cells (iMSCs) may be employed as a research tool for avoiding these problems. The purpose of this review was to revise the available literature on the characteristics of the iMSC lines, paying special attention to the maintenance of the phenotype of the primary cells from which they were derived, and whether they are effectively useful for in vitro disease modeling and cell therapy purposes. This review was performed by searching on Web of Science, Scopus, and PubMed databases from 1 January 2015 to 30 September 2019. The keywords used were ALL = (mesenchymal AND ("cell line" OR immortal*) AND (cartilage OR chondrogenesis OR bone OR osteogenesis) AND human). Only original research studies in which a human iMSC line was employed for osteogenesis or chondrogenesis experiments were included. After describing the success of the immortalization protocol, we focused on the iMSCs maintenance of the parental phenotype and multipotency. According to the literature revised, it seems that the maintenance of these characteristics is not guaranteed by immortalization, and that careful selection and validation of clones with particular characteristics is necessary for taking advantage of the full potential of iMSC to be employed in bone and cartilage-related research.

The phenomenon of cancer cell heterogeneity has been explained by different hypotheses, each entailing different therapy strategies. The most recent is the cancer stem cell model, which says that tumourigenicity and self-renewal are restricted to rare stem cell-like cancer cells. Since its conception, conflicting evidence has been published. In this study, we tested the applicability of a new approach developed in the field of ecology, the hierarchy-of-hypotheses approach, for the Cancer Stem Cell hypothesis. This approach allows to structure a broad concept into more specific sub-hypotheses, which in turn can be connected to available empirical studies. To generate a dataset with empirical studies, we conducted a systematic literature review in the Web of Science limited to the first 1000 publications returned by the search. From this pool, 51 publications were identified that tested whether a cell sub-population had cancer stem cell properties. By classifying the studies according to: (1) assessed indicators, (2) experimental assays and (3) model cancer cells used, we built a hierarchical structure of sub-hypotheses. The empirical tests from the selected studies were subsequently assigned to this hierarchy of hypotheses, and the percentage of supporting, undecided and questioning evidence was calculated for each sub-hypothesis, as well as additional experimental characteristics. Our approach successfully allowed us to determine that within our dataset, the empirical support for the CSC hypothesis was only 49.0%. The support of different sub-hypotheses was highly variable. Most noticeable, the conception that putative cancer stem cells are a rare subset of cells could not be confirmed by most studies (13.5% support). The empirical support varied also between types of cancer, animal models and cell isolation method used. For the first time, this study showed the applicability of the hierarchy-of-hypotheses approach for synthesizing and evaluating empirical evidence for a broad hypothesis in the field of bio-medical research.

Considering the structural loss that occurs after surgical procedures for cystic and tumoral pathology, in periodontitis, as well as the maxillary atrophy that determines the rehabilitation with dental implants, it is imperative to find satisfactory solutions. The opportunity provided by the findings in stem cells is a recent introduction in the field of oral surgery, based on the regenerative potential that these cells possess in order to restore defects at different levels of the oral cavity. The aim of this systematic review is to discover the real applications that stem cells may have in our treatments in the near future.

Klinefelter syndrome (KS) has been defined by sex chromosome aneuploidies (classically 47, XXY) in the male patient. The peripubertal timeframe in KS patients has been associated with the initiation of progressive testicular fibrosis, loss of spermatogonial stem cells (SSC), hypogonadism and impaired fertility. Less than half of KS patients are positive for spermatozoa in the ejaculate or testis via semen analysis or testicular sperm extraction, respectively. However, the chance of finding spermatogonia including a sub-population of SSCs in KS testes has not been well defined. Given the recent demonstration of successful cell culture for mouse and human SSCs, it could be feasible to isolate and propagate SSCs and transplant the cells back to the patient or to differentiate them in vitro to haploid cells.

Mesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.

Different delivery mechanisms have been proposed in the literature for targeted therapies in the treatment of lymphedema. They vary from simple and direct injection to sophisticated induction of gene expression in a targeted tissue. We conducted a systematic review of publications assessing the use of viral vectors for gene transfer in lymphedema treatment. We hypothesized that viral vectors are an effective way to deliver targeted therapy in lymphedema treatment. We conducted a comprehensive systematic review of the published literature on targeted therapies associated with lymphedema surgery using the PubMed database. Eligibility criteria excluded papers that reported use of viral vectors for other medical conditions. Abstracts, presentations, reviews, meta-analyses, and non-English language articles were also excluded. From 21 potential articles found in the literature, fourteen fulfilled study eligibility criteria. Positive outcomes in terms of lymphangiogenesis were seen. The viral vectors used included adenovirus and recombinant adeno-associated virus. Most of the genes expressed were growth factors, but expression of dominant-negative transforming growth factor-β1 receptor-II or Prox1 was also proposed. Five studies targeted genetic expression on lymphedema tissue, five on transplanted lymph nodes, two on skeletal muscle, and one on adipose-derived stem cells. Publications assessing use of viral vectors for gene transfer in lymphedema treatment demonstrated that it is an effective mechanism of delivering targeted therapies. However, to date, all studies were experimental and further studies must be performed before translating these therapies into clinical practice.

Mesenchymal stem cells are pluripotent cells that have the ability to generate cells from a cell line or in other cell types from different tissues but from the same origin. Although those cells have more limited differentiation capacity than embryonic stem cells, they are easily obtained from somatic tissue and can be grown in large quantities. This characteristic of undifferentiated stem cells differentiating into different cell lines arouses strategies in regenerative medicine for the treatment of different diseases such as neurodegenerative diseases.

Trauma- or osteoarthritis-related cartilage damage resulted in functional decline of joints and heavy burden of public health. Recently, the reparative role of mesenchymal stem/progenitor cells (MSCs) in articular cartilage (AC) reconstruction is drawing more and more attention.

Meniscus injuries are among the most common athletic injuries and result in functional impairment in the knee. Repair is crucial for pain relief and prevention of degenerative joint diseases like osteoarthritis. Current treatments, however, do not produce long-term improvements. Thus, recent research has been investigating new therapeutic options for regenerating injured meniscal tissue. This review comprehensively details the current methodologies being explored in the basic sciences to stimulate better meniscus injury repair. Furthermore, it describes how these preclinical strategies may improve current paradigms of how meniscal injuries are clinically treated through a unique and alternative perspective to traditional clinical methodology.

Multiple sclerosis (MS) typically arises in early/middle adulthood and is characterized by a progressive disability of the central nervous system (CNS). Currently approved therapies do not promote tissue repair or stop disease progression. Emerging data demonstrate that stem cells present a great potential in regenerative medicine and, consequently, have also been widely investigated as a potential treatment for MS. Therefore, the aim of this study was to conduct a systematic review to inquire into the safety, tolerability, and efficacy of mesenchymal stem cells (MSCs) therapies in MS.

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with significant morbidity and mortality, and it often leads to poor clinical outcome. Although great efforts have been made toward animal and clinical studies, optimal therapy of SAH remains a challenge for scientists and clinicians. Increasing evidence suggests that stem-cell-based therapies may provide innovative approaches for treatment of SAH-related disability. In this review, we summarized the recent advances in stem cell research in SAH. Neuroregeneration after SAH could be conducted by the activation of endogenous neural stem cells (NSCs), transplantation of external stem cells, or reprogramming non-neuronal cell to neurons. The potential mechanism and signaling pathways, as well as the efficiency and safety of these stem cell treatments, were discussed in detail. Although lots of challenges remain for translating the laboratory findings and technologies into clinical therapies, these research studies provided the foundation and guidance for using different resources of stem cells as a brain repair strategy after SAH.

Previous studies have found that bone mesenchymal stem cells (BMSCs) were capable of self-replication, multi-differentiation, and regeneration. The aim of this study was to carry out a systematic review and meta-analysis of the efficacy of BMSC therapy for ovariectomized rats.

Infertility is a major problem worldwide. Various strategies are being used to develop better treatments for infertility and The most trending strategy is the stem cell therapy. In this study, the literature on stem cell therapy for ovarian disorders is summarized with analysis of current developments.

Regenerative stem cell-based therapies for bronchopulmonary dysplasia (BPD), the most common preterm birth complication, demonstrate promise in animals. Failure to objectively appraise available preclinical data and identify knowledge gaps could jeopardize clinical translation. We performed a systematic review and network meta-analysis (NMA) of preclinical studies testing cell-based therapies in experimental neonatal lung injury. Fifty-three studies assessing 15 different cell-based therapies were identified: 35 studied the effects of mesenchymal stromal cells (MSCs) almost exclusively in hyperoxic rodent models of BPD. Exploratory NMAs, for select outcomes, suggest that MSCs are the most effective therapy. Although a broad range of promising cell-based therapies has been assessed, few head-to-head comparisons and unclear risk of bias exists. Successful clinical translation of cell-based therapies demands robust preclinical experimental design with appropriately blinded, randomized, and statistically powered studies, based on biological plausibility for a given cell product, in standardized models and endpoints with transparent reporting.

Background: Symptomatic cartilage lesions and early osteoarthritis produce significant clinical and economic burdens. Cartilage repair can improve the symptoms and delay arthroplasty. The complete healing of damaged cartilage with the consistent reproduction of normal hyaline cartilage has not yet been achieved. The choice of harvesting site might influence the cells' abilities to modulate immunologic and inflammatory responses. Recently, dental pulp has been shown to contain a stem cell niche consisting of dental pulp stem cells (DPSCs) that maintain their self-renewal capacity due to the active environment in the dental pulp of deciduous teeth. Objective: The aim of this study was to critically review the current literature on the potential and limitations of the use of dental pulp-derived mesenchymal stem cells in cell-based therapies for cartilage regeneration. Methods: An electronic, customized search of scientific articles was conducted using the PubMed/MEDLINE and EMBASE databases from their inception to December 2018. The inclusion criteria were applied, and the articles that described the use of DPSC in cartilage treatment were selected for complete evaluation. The articles were classified according to the scaffold used, experimental model, chondrogenic differentiation features, defect location, cartilage evaluation, and results. After the application of the eligibility criteria, a total of nine studies were selected and fully analyzed. Results: A variety of animal models were used, including mice, rats, rabbits, and miniature pigs, to evaluate the quality and safety of human DPSCs in the repair of cartilage defects. Among the articles, two studies focused on preclinical models of cartilage tissue engineering. Five studies implanted DPSCs in other animal sites. Conclusion: The use of DPSCs is a potential new stem cell therapy for articular cartilage repair. The preclinical evidence discussed in this article provides a solid foundation for future clinical trials. Impact statement Osteoarthritis presents an ever-increasing clinical and socioeconomic burden. While cartilage repair has the potential to improve symptoms and delay joint replacement, complete regeneration of hyaline cartilage has been an elusive goal. Dental pulp has been shown to contain a niche that protects dental pulp stem cells (DPSCs) from the cumulative effects of genetic and environmental factors and maintains their self-renewal capacity due to the active environment. Transplantation and preclinical trials have demonstrated the strong potential of regenerative tissue-engineering protocols using DPSCs.