Current Stem Cell Research & Therapy - Volume 13, Issue 4, 2018

Background: Numerous articles have been published on the potential of using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in clinical applications. As these types of stem cell are well studied, the research on germline stem cells (GSCs), which hold a huge potential for clinical application and permanent treatment for infertility, is left behind. Besides possessing the characteristics of being able to self-renew and to give rise to differentiated progeny throughout postnatal life, the potential of GSCs to transform into pluripotent status is remarkable but is unexploited. Objective: To explore the potential of germline stem cells in therapeutic usage, it's required to understand the underlying transformation mechanism of germline stem cells into pluripotent cells. Results: In this review, we summarized development of ESCs, GSCs, iPSCs, and embryonic stem-like (ES-like) cells derived from GSCs, discussed feasibility and the technical hurdles of using these types of stem cells in therapeutic cloning, and finally focused on the comparison of the ESCs, iPSCs and ESlike cells in current as well as potential applications in medicine. Moreover, the prospects of female germline stem cells (FGSCs) and their derived ES-like cells were also discussed as a novel alternative in clinical application. Conclusion: With the capacity of germline reconstitution and transformation into pluripotent status, GSCs possess significant potential for clinic usage and therapeutic cloning.

Background: Induced pluripotent stem cells hold tremendous potential for biological and therapeutic applications. The development of efficient technologies for targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. The revolutionary technology for genome editing known as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) system is recently recognized as a powerful tool for editing DNA at specific loci. Objective: The ease of use of the CRISPR-Cas9 technology will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. More recently, this system was modified to repress (CRISPR interference, CRISPRi) or activate (CRISPR activation, CRISPRa) gene expression without alterations in the DNA, which amplified the scope of applications of CRISPR systems for stem cell biology. Results and Conclusion: Here, we highlight latest advances of CRISPR-associated applications in human pluripotent stem cells. The challenges and future prospects of CRISPR-based systems for human research are also discussed.

Background: Regenerative medicine aims to provide therapeutic treatment for disease or injury, and cell-based therapy is a newer therapeutic approach different from conventional medicine. Ethical issues that rose by the utilisation of human embryonic stem cells (hESC) and the limited capacity of adult stem cells, however, hinder the application of these stem cells in regenerative medicine. Recently, isolation and characterisation of c-kit positive cells from human amniotic fluid, which possess intermediate characteristics between hESCs and adult stem cells, provided a new approach towards realising their promise for fetal and adult regenerative medicine. Despite the number of studies that have been initiated to characterize their molecular signature, research on developing approaches to maintain and enhance their regenerative potential is urgently needed and must be developed. Aim: Thus, this review is focused on understanding their potential uses and factors influencing their pluripotent status in vitro. Conclusion: In short, this cell source could be an ideal cellular resource for pluripotent cells for potential applications in allogeneic cellular replacement therapies, fetal tissue engineering, pharmaceutical screening, and in disease modelling.

Background: Revascularisation therapy is the current gold standard of care for critical limb ischemia (CLI), although a significant proportion of patients with CLI either are not fit for or do not respond well to this procedure. Recently, novel angiogenic therapies such as the use of autologous cellbased therapy (CBT) have been examined, but the results of individual trials were inconsistent. Objective: To pool all published studies that compared the safety and efficacy of autologous CBT derived from different sources and phenotypes with non cell-based therapy (NCT) in CLI patients. Methods: We searched Medline, Embase, Cochrane Library and ClinicalTrials.gov from 1974-2017. Sixteen randomised clinical trials (RCTs) involving 775 patients receiving the following interventions: mobilised peripheral blood stem cells(m-PBSC), bone marrow mononuclear cells(BM-MNC), bone marrow mesenchymal stem cells(BM-MSC), cultured BM-MNC(Ixmyelocel-T), cultured PB cells(VesCell) and CD34+ cells were included in the meta-analysis. Results: High-quality evidence (QoE) showed similar all-cause mortality rates between CBT and NCT. AR reduction by approximately 60% were observed in patients receiving CBT compared to NCT (moderate QoE). CBT patients experienced improvement in ulcer healing, ABI, TcO2, pain free walking capacity and collateral vessel formation (moderate QoE). Low-to-moderate QoE showed that compared to NCT, intramuscular BM-MNC and m-PBSC may reduce amputation rate, rest pain, and improve ulcer healing and ankle-brachial pressure index, while intramuscular BM-MSC appeared to improve rest pain, ulcer healing and pain-free walking distance but not AR. Efficacy of other types of CBT could not be confirmed due to limited data. Cell harvesting and implantation appeared safe and well-tolerated with similar rates of adverse-events between groups. Conclusion: Implantation of autologous CBT may be an effective therapeutic strategy for no-option CLI patients. BM-MNC and m-PSBC appear more effective than NCT in improving AR and other limb perfusion parameters. BM-MSC may be beneficial in improving perfusion parameters but not AR, however, this observation needs to be confirmed in a larger population of patients. Generally, treatment using various sources and phenotypes of cell products appeared safe and well tolerated. Large-size RCTs with long follow-up are warranted to determine the superiority and durability of angiogenic potential of a particular CBT and the optimal treatment regimen for CLI.

Background: Fracture non-union is a significant problem with a wide range demographic and massive socioeconomic elements, as well as the clinical difficulties it presents. Conventional treatments with autograft and allograft bone grafting pose serious difficulties, thus, it is necessary to develop novel techniques with our ever increasing knowledge of bioengineering using natural materials. Objective: To search for current evidence regarding the treatment of fracture non-union or bone defects using mesenchymal stem cells (MSCs). Results: The results presented in this review show that the use of mesenchymal stem cells for the treatment of non-union and bone defects is optimistic. Several papers had positive outcomes to report. There is a need for higher level evidence. Conclusion: A strong need of clinical results is required to further progress in cell therapy. Launched trials will hopefully provide this information in the near future. If clinical trials are positive, further development of complex tissue engineering techniques may be developed to treat large bone defects.

Background: Currently, antibodies are progressively applied in medicine for different purposes, including diagnostic and therapeutic indications. Over twenty monoclonal antibodies utilized for many therapeutic reasons from therapy of cancers, immune disorders, and osteoporosis to localized bony defects. In addition, therapeutic antibodies represented various findings in bone tissue engineering. Objectives: The current study aims to systematically review the available literature on antibody assisted bone regeneration in animal models. Methods: A through electronic search was conducted from January 1992 to June 2017 limited to English language publications on administrations of antibodies for bone regeneration. Data extraction was ere performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Twenty studies were selected and analyzed in this systematic review. Among these studies, six articles reported in vitro results in addition to in vivo evaluations. The data is tabulated according to the route of administrations as locally administrated antibody which includes anti-bone morphogenetic protein 2 (anti-BMP2) and systemic administrated antibodies, which include anti-sclerostin and anti- Dickkopf-1 (DKK1). Data are summarized and reported by the following variables: Type of study, types of cells for in vitro investigations, types of animal models and defects characteristics, types of scaffolds used in the defect site, duration of follow-ups; and outcomes of assessments. Conclusions: A novel approach of administration of antibodies demonstrated promising results for bone tissue engineering. However, more investigations, particularly in larger animals, are required for their further possible clinical administration.

Spinal surgery presents a challenge for both neurosurgery and orthopaedic surgery. Due to the heterogeneous differentiation potential of mesenchymal stem cells, there is much interest in the treatment of spine surgery. Animal and human trials focussing on the efficacy of mesenchymal stem cells in spinal cord injury, spine fusion and disc degeneration were included in this systematic review. Published articles up to January 2016 from MEDLINE, PubMed and Ovid were used by searching for specific terms. Of the 2595 articles found, 53 met the selection criteria and were included for analysis (16 on spinal cord injury, 28 on intervertebral disc repair and 9 on spinal fusion). Numerous studies reported better results when the mesenchymal stem cells were used in co-culture with other cells or used in scaffolds. Mesenchymal stem cells were also found to have an immune-modulatory role, which can improve surgical outcome. This systematic review suggests that mesenchymal stem cells can be used safely and effectively for these spinal surgery treatments. Whilst, in certain studies, mesenchymal stem cells did not necessarily show improved results from existing treatments, they provide an alternative option. This can reduce morbidity that arises from current surgical treatment.