Current Stem Cell Research & Therapy - Volume 16, Issue 3, 2021

Pluripotent Stem Cells [PSCs] are emerging as an excellent cellular source for the treatment of many degenerative diseases such as diabetes, ischemic heart failure, Alzheimer’s disease, etc. PSCderived pancreatic islet β-cells appear to be a promising therapy for type 1 diabetic patients with impaired β-cell function. Several protocols have been developed to derive β-cells from PSCs. However, these protocols produce β-like cells that show low glucose stimulated insulin secretion (GSIS) function and mirror GSIS profile of functionally immature neonatal β-cells. Several studies have documented a positive correlation between the sirtuins (a family of ageing-related proteins) and the GSIS function of adult β-cells. We are of the view that the GSIS function of PSC-derived β-like cells could be enhanced by improving the function of sirtuins in them. Studying the sirtuin expression and activation pattern during the β-cell development and inclusion of the sirtuin activators and inhibitor cocktail (specific to a developmental stage) in the present protocols may help us derive functionally mature, ready-to-use β- cells in-vitro making them suitable for transplantation in type 1 diabetes.

Avian embryos and related cell lines have found wide applications in basic and applied sciences. The embryonated egg is a great host for monoclonal antibodies and recombinant proteins. Avian cell lines derived from embryonated eggs have been used for the production of transgenic birds and virus inoculation in vaccine preparation. Hitherto, many efforts have been invested to develop efficient avian stem cell culture. Under the conventional conditions, there are various challenges, such as the type of feeder layers, conditioned medium, serum, and growth factors. Researchers have investigated different conditions to solve these problems. Recent studies have shown that targeted strategies using small molecule inhibitors could be used as alternatives to multi-growth factor delivery approaches. Since small molecule inhibitors were used for mammalian pluripotent stem cells (PSC), several kinds of research have examined the effect of the small molecule on self- -renewal and maintenance of avian PSC. Avian PSC can be derived from early blastodermal cells (stage X), circular primoridial germ cells (PGC; stage HH17), gonadal PGC (stage HH28), and embryonic germ cells (EGC; HH28). Previous studies have shown that the use of small molecule drugs such as PD0325901, SB431542, SC1, IDE1, Z-VAD, Blebbistatin, H-1152, and IDE1 could be an efficient method for the derivation of avian stem cells. This mini-review covers the recent development of avian stem cell culture by small molecules.

Mesenchymal stromal cells (MSCs) regulate other cell types through a strong paracrine component called the secretome, comprising several bioactive entities. The composition of the MSCs’ secretome is dependent upon the microenvironment in which they thrive, and hence, it could be altered by pre-conditioning the MSCs during in vitro culture. The primary aim of this review is to discuss various strategies that are being used for the pre-conditioning of MSCs, also known as “priming of MSCs”, in the context of improving their therapeutic potential. Several studies have underscored the importance of extracellular vesicles (EVs) derived from primed MSCs in improving their efficacy for the treatment of various diseases. We have previously shown that co-culturing hematopoietic stem cells (HSCs) with hypoxia-primed MSCs improves their engraftment potential. Now the question we pose is, would priming of MSCs with hypoxia favorably alter their secretome? and would this altered secretome work as effectively as the cell to cell contact did? Here we review the current strategies of using the secretome, specifically the EVs (microvesicles and exosomes), collected from the primed MSCs with the intention of expanding HSCs ex vivo. We speculate that effective priming of MSCs in vitro could modulate the molecular profile of their secretome, which could eventually be used as a cell-free biologic in clinical settings.

Abstract: Stem cells are undifferentiated cells with the ability to proliferate and convert to different types of differentiated cells that make up the various tissues and organs in the body. They exist both in embryos as pluripotent stem cells that can differentiate into the three germ layers and as multipotent or unipotent stem cells in adult tissues to aid in repair and homeostasis. Perturbations in these cells’ normal functions can give rise to a wide variety of diseases. In this review, we discuss the origin of different stem cell types, their properties and characteristics, their role in tissue homeostasis, current research, and their potential applications in various life-threatening diseases. We focus on neural stem cells, their role in neurogenesis and how they can be exploited to treat diseases of the brain including neurodegenerative diseases and cancer. Next, we explore current research in Induced Pluripotent Stem Cells (iPSC) techniques and their clinical applications in regenerative and personalized medicine. Lastly, we tackle a special type of stem cells called Cancer Stem Cells (CSCs) and how they can be responsible for therapy resistance and tumor recurrence and explore ways to target them.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since Dec 2019, known as COVID-19 or 19-nCoV, has led to a major concern of the potential for not only an epidemic but a pandemic in China and now it seems to be a public health problem all over the world. The general mortality rate of the COVID-19 was about 3%. However, the mortality risk seems to be a significant increase in elderly and cases with chronic disease, who are more likely to develop into acute respiratory distress syndrome (ARDS). There still lacks effective methods for ARDS of COVID-19 patients and the prognosis was poor. Mesenchymal Stem Cells (MSCs) based treatment has the advantage of targeting numerous pathophysiological components of ARDS by secreting a series of cell factors, exerting anti-inflammatory, antioxidative, immunomodulatory, antiapoptotic, and proangiogenic effects, resulting in significant structural and functional recovery following ARDS in various preclinical models. Recently, pilot clinical studies indicated MSCs based therapy was promise in treatment of ARDS caused by SARS-CoV-2. However, little is known about MSCs therapy for ARDS caused by COVID-19.

Head and Neck Squamous Cell Carcinoma (HNSCC) is categorized as the sixth most common cancer worldwide, with an incidence of more than 830,000 cases per year and a mortality rate of 50%. Tobacco use, alcohol consumption, and Human Papillomavirus infection are the prominent risks for HNSCC. Despite significant developments in the treatment of HNSCC, a high rate of recurrences makes the clinical situation worse and results in poor survival rates. Recent perspectives demonstrate that although epithelial transformation plays a crucial role in cancer development, tumor surrounding microenvironment takes part in the progression of cancer as well. Cancer Stem Cells (CSCs), which harbor unlimited self-renewal capacity, have a crucial role in the growth of HNSCC and this cell population is responsible for tumor recurrence unless eliminated by targeted therapy. CSCs are not only a promising target for tumor therapy but also a crucial biomarker to determine the patients at high risk for undetermined results and disease development, just as the bone marrow, which is the niche of hematopoietic and mesenchymal stem cells, is important for stem cell maintenance. Similarly, the concept of microenvironment is also important for the maintenance of CSCs. Apart from the cell-cell interactions, there are many parameters in the cancer microenvironment that affect the development of cancer, such as extracellular regulation, vascularization, microbial flora, pH, and oxygenation. The purpose of this review is to introduce HNSCC, explain the role of CSCs and their microenvironment, and refer to the conventional and novel targeted therapy for HNSCC and CSCs.

Background: Given the minimal capacity and sometimes the failure of the mammalian nervous system to regenerate and repair itself after damage, strategies are required to help enhance this regenerative process. Adipose-derived Mesenchymal Stem Cells (ADMSCs) are likely candidates to assist in the recovery process due to their ability to differentiate into neural cells. Successful implementation of this intervention in a clinical setting would increase the rate of recovery following traumatic brain injury. Review: Various strategies have been attempted to differentiate ADMSCs into neural cells for clinical use. Such methods have not been entirely successful in the development of functioning specialized cells for subsequent practical use. Therefore, the implementations of this differentiation technique in the clinical trial have not been effective. In this article, the potential of differentiating ADMSCs into neural cells and the various methods employed, including biological induction, chemical induction and photobiomodulation (PBM) will be discussed, where the combined use of transducers and PBM for neural differentiation of ADMSCs is also deliberated. Conclusion: PBM shows promise as an avenue for effective ADMSCs differentiation into neural cells and their proliferation. Applying PBM with optimized biological factors and chemical inducers may prove to be an effective tool for clinical application.

Mesenchymal Stem Cells (MSCs) are one of the most promising tools for cell therapy, that are isolated from bone marrow and many other adult tissues such as liver, cord blood, placenta, dental pulp and adipose tissue. Due to the lack of MHC class II expression on the surface of MSCs, they can also be used as a potent cell source for tissue regeneration in non-autologous cell therapy applications. Many advantages of MSCs such as their self-renewal, in vitro proliferation, rapid cell doubling capacity, anti-fibrotic, anti-apoptotic, anti-inflammatory, immunomodulatory and immunosuppressive effects, and also paracrine nature have been demonstrated in various pre-- clinical studies and clinical evidence. The ability of MSCs to differentiate into multiple cell lineages, as well as the lack of ethical issues in comparison with embryonic and induced Pluripotent Stem Cells (iPSCs), has introduced them as a suitable candidate for cell therapy. This review provides a comprehensive overview of various clinical trials based on MSCs for the treatment of a variety of diseases, demonstrating their capability in the treatment of dermatological, musculoskeletal, neurological, cardiovascular, respiratory, renal, gastroenterological and urological conditions, etc.

Background: Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating Heart Failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy are not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. Methods: We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized Controlled Trials (RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model by the use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was safely assessed by death and rehospitalization and the secondary outcome was efficacy, which was assessed by six-minute walk distance and Left Ventricular Ejection Fraction (LVEF), Left Ventricular End-systolic Volume (LVESV), Left Ventricular End-diastolic Volume (LVEDV) and Brain Natriuretic Peptide (BNP). Results: A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT. MSCs transplantation significantly improved Left Ventricular Ejection Fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased Left Ventricular End-Systolic Volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, - 12.83], p<0.00001) and Left Ventricular End-Diastolic Volume (LVEDV) by 5.78 ml (MD [95% CI]=- 5.78[-12.00, 0.43], p=0.07), in the MSCs group, BNP was decreased by 133.51 pg/ml MD [95% CI]= - 133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. Conclusion: Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure are safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*108 cells were of better effect.