Current Stem Cell Research & Therapy - Volume 16, Issue 4, 2021

Cancer Stem Cells (CSCs) are responsible for tumor development, invasion and metastasis and resistance to chemotherapy and radiotherapy. Therefore, treatment strategies have turned to targeting CSCs, and utilizing nanotechnological approaches to target CSCs has become increasingly fascinating. Functionalized nanoparticles (NPs), such as metallic NPs, liposomes, polymeric NPs, albumin microspheres and nanomicelles, can easily cross the cytoplasmic membrane and accumulate at their targets to continuously release therapeutic agents in response to the characteristics of the tumor microenvironment. Different kinds of NPs possess different characteristics. Inducing immune responses might be the disadvantage they commonly owned through the summary and analysis of these NPs. For natural polymers, they have many attractive properties, but deficiencies also exist such as poor water-solubility, high viscosity, high permeability, etc. The drug-encapsulated NPs launched in the market and those in the clinical trials exhibit a bright prospect in cancer targeted therapy. In addition, the application of nanodiagnostic techniques, such as nanocantilever and DNA microarray technology and early cancer detection has become an indispensable component in clinical practice to improve in vivo detection and enhance targeting efficiency. This review mainly determines the species and usages of NPs in drug delivery and disease diagnosis, the delivery mechanisms of NPs, the main factors that affect nanomedicine efficiency and toxicity and the further trends in the development of targeted therapy. Nevertheless, more and deeper investigations are still needed to avert potential adverse effects and improve the delivery efficiency to achieve better therapeutic effects.

Background: Cell-based therapies represent one of the definitive treatment approaches to SCI which, to become a routine clinical application, is marred by several known unknowns. The Bone Marrow Mononuclear Cells (BMMNCs) and Mesenchymal Stem Cells (MSCs) represent the most clinically applied cell types for SCI in humans, with safety established, and to an extent, efficacy reported. Methods: In this review, we have analysed the clinical studies performed using BMMNC and MSC for complete SCI separately, and the potential for applying those cells in combination. We have also analysed those factors whose outcome in animal studies of SCI could be evaluated in depth but the clinical outcome cannot be evaluated intrinsically owing to practical difficulties. Conclusion: A combination of these two cell types, BMMNC and MSC, has been proven to be advantageous than applying them separately. Therefore, a thorough evaluation including the rationale and potential implications of applying these two therapies has been presented here, and we hypothesize that such a combination is likely to improvise the outcome of a wholesome approach to spinal cord regeneration after SCI.

Human Pluripotent Stem Cells (PSCs), including Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs), have the remarkable potential to self-renew and develop into various cell lineages. Human Mesenchymal Stem Cells (MSCs) or multipotent stem cells that are present in various organs can self-renew and differentiate into multiple mesenchymal lineages. Both human PSCs and MSCs hold great promise in cell-based therapies, disease modeling, drug discovery, and regenerative medicine. Human stem cells must be cultured under the optimal conditions to use them in transplantology. Therefore, researchers must ensure the sterility of human stem cell lines. Bacterial contamination is a common problem in laboratories and major precautions are required to detect the types of microorganisms, and to eliminate and prevent contamination in cell cultures. Stem cell culture media usually contain antibiotics and antimycotics such as penicillin- streptomycin (pen-strep), gentamicin, and amphotericin B (AmB) to avoid bacterial, fungal, and yeast contaminants. Numerous publications recognized the serious effect of antibiotics and antimycotics on in vitro properties of human stem cells, including proliferation, differentiation, survival, and genetic instability. This review study aimed to understand the impact of routinely used antibiotics and antimycotics such as pen-strep, gentamicin, and AmB on viability, proliferation, and functional properties (differentiation and pluripotency) of human PSCs and MSCs.

COVID-19 pandemic is a global health crisis of the 21st Century. There are currently no approved vaccines and no particular anti-viral treatment for coronavirus disease. As COVID-19 has a broad range of illnesses, it is necessary to find a safe and effective therapeutic method for COVID-19. An attractive approach for treating COVID-19 is cell therapy. Cell therapy aims to inject new and healthy stem cells into a patient’s body, to repair the damaged cells and tissues. Stem cell therapy is one of the most studied and important approaches in the treatment of COVID-19 these days. The significant clinical outcome was observed by the adoptive transfer of stem cells, specifically mesenchymal stem cells. This study reviews the characteristics of stem cells and clinical trials that have used stem cells in treating COVID-19.

Diseases, trauma, and injuries are highly prevalent conditions that lead to many critical tissue defects. Tissue engineering has great potentials to develop functional scaffolds that mimic natural tissue structures to improve or replace biological functions. In many kinds of technologies, electrospinning has received widespread attention for its outstanding functions, which is capable of producing nanofibre structures similar to the natural extracellular matrix. Amongst the available biopolymers for electrospinning, poly (caprolactone) (PCL) has shown favorable outcomes for tissue regeneration applications. According to the characteristics of different tissues, PCL can be modified by altering the functional groups or combining with other materials, such as synthetic polymers, natural polymers, and metal materials, to improve its physicochemical, mechanical, and biological properties, making the electrospun scaffolds meet the requirements of different tissue engineering and regenerative medicine. Moreover, efforts have been made to modify nanofibres with several bioactive substances to provide cells with the necessary chemical cues and a more in vivo like environment. In this review, some recent developments in both the design and utility of electrospun PCL-based scaffolds in the fields of bone, cartilage, skin, tendon, ligament, and nerve are highlighted, along with their potential impact on future research and clinical applications.

Mesenchymal stem cells, because of their high proliferation, differentiation, regenerative capacity, and ease of availability, have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and act against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra- cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that act as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as they are the leading members of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

Mesenchymal Stem Cells (MSCs) enable a novel approach to stem cell therapy. Bone Marrow (BM) was the first source used in MSCs therapy. However, BM has a number of key limitations as a source of MSCs, such as the existence of only a small number of MSCs in the tissue; the painful, ethically problematic, and invasive nature of the associated collection process; and a decrease in MSC specifications as the age of donors increases. As a result, there has been increasing scholarly attention towards identifying alternative sources for MSCs. In specific, Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) have been identified as a valuable source from which MSC may be obtained with potentially fewer ethical issues. MSCs can regulate the immune response, promote tissue repair, increase regeneration, and improve anticancer effects. Thus, they are significant allogenic and autologous representatives for curing malignant and non-malignant disorders. In this review, therefore, the prospective applications for curing autoimmune disorders will be considered.

The cause of Coronavirus Disease 2019 (COVID-19) known as the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly designated 2019-nCoV) was first discovered in December 2019 in Wuhan, China. It then spread rapidly worldwide. Investigation for the discovery of drugs to cure this disease continues. The currently accepted treatments are supportive, but there is no specific disease curing intervention found yet. Since mid-February, therapies involving Mesenchymal Stem/Stromal Cells (MSCs) have been proposed for the treatment of patients with COVID-19. In light of these recent developments, this review will focus on: i) the mechanism of SARS-CoV-2 action and the subsequent pathology in COVID-19, ii) the proposed mechanism( s) of outcome-improving action of MSCs or MSC-derived extracellular vesicles in COVID-19 pneumonia, iii) registered MSC-based clinical trials and interventions for the treatment of COVID-19, iv) published case studies/series/trials reporting the use of MSC-based treatments in COVID-19 cases, and finally v) the need for authority regulations and clinical guidelines for MSCbased treatment strategies for COVID-19.

The objective of this review was to answer two critical questions in the cell-based bone defect therapies that were as follows: 1) does cell therapy associate with the increase in the occurrence of adverse events in the patients compared to control groups, 2) does the use of various cell therapy approaches, including More-than Minimal Manipulation (MMM) and Minimal Manipulation (MM), affect the occurrence of adverse events? An electronic literature search was performed in five databases. The controlled clinical trial studies were selected according to the eligibility criteria. Then, they were categorized into MMM and MM approaches, and a meta-analysis of the controlled clinical trials on the occurrence of adverse events was conducted. 23 controlled clinical trials, including 10 MMM (n=341 patients) and 13 MM (n=503 patients) approaches were assessed in this study. Bone defects were oral-maxillofacial defects (7MMM and 8MM), osteonecrosis of the femoral head (1MMM and 5MM), long bone shaft fracture (1MMM), and bone defect during revision total hip arthroplasty (1MMM). Cells were isolated from various tissues such as bone marrow (5MMM and 10MM), the dental pulp (2MMM and 2MM), adipose tissue (2MMM), periosteum (1MMM), and peripheral blood (1MMM). Notably, the adverse events were reported in 37 patients, and 3 patients in MMM and MM approaches, respectively. A meta-analysis demonstrated that there was no association between cell therapy and the occurrence of adverse events. Also, the MMM approach (OR: 1.46) has a higher chance of the occurrence of adverse events compared to the MM approach (OR: 0.71). These results suggested that cell therapy, specifically the MM approach, is safe to improve bone regeneration. Also, future systematic reviews should evaluate the efficacy of these cell therapy approaches.