Current Stem Cell Research & Therapy - Volume 16, Issue 2, 2021

A novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has emerged in Wuhan, China since the end of December 2019 and has quickly spread all over the world in a matter of two months. To date, no specific treatment has been proven to be effective for coronavirus (COVID-19). With the rapid increase of infected patients and deaths, it is vital to explore an effective treatment for COVID-19. Current studies suggest that there exists cytokine storm in SARS-CoV-2-infected patients; some of the them will develop acute respiratory distress syndrome (ARDS) and multiple organ dysfunction, and even death. Mesenchymal stem cells (MSCs) possess the property of immunomodulation. Given the previous preclinical and clinical studies, MSCs therapy has shown safety and efficacy in the treatment of respiratory failure or ARDS. Based on similar principles, MSCs therapy may also be an effective therapy in the treatment of COVID-19. In this study, we summarized the clinical outcomes of MSCs for ARDS patients in some preclinical and clinical studies and discussed the application of MSCs for patients with COVID-19 in China and the related important issues with MSCs used during the outbreak.

Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of optic nerverelated permanent visual impairment among individuals of over 50 years of age after glaucoma. Due to perplexing disorder regarding its pathogenesis, there is still no widely accepted and established treatment plan. Mesenchymal stem cells (MSCs) are one of the rare stem cell types that therapeutic agents for immunomodulation and ischemic tissue repair in clinical practice. However, there are certain disadvantages in using MSCs, such as potential tumorigenicity, need for autologous collection, and short survival time. Previous evidence suggested that MSC-exosome significantly attenuated post-ischemic neuronal damage and induced long-term neuroprotection associated with enhanced angiogenesis in MSCs. Therefore, we hypothesized that the intravitreal administration of MSC-exosome could be a potentially effective therapeutic approach for NAION by using a similar mechanism via promoting angiogenesis, neuro-regeneration, and neurological recovery, suppressing oxidative stress and reducing apoptosis, and suppressing inflammation and immunity based on its biological structure and function in NAION. Questions that need to be answered before testing clinically include dose regimen, injection frequency, the optimal duration of treatment, and duration of medication.

The method of cellular reprogramming using small molecules involves the manipulation of somatic cells to generate desired cell types under chemically limited conditions, thus avoiding the ethical controversy of embryonic stem cells and the potential hazards of gene manipulation. The combinations of small molecules and their effects on mouse and human somatic cells are similar. Several small molecules, including CHIR99021, 616452, A83-01, SB431542, forskolin, tranylcypromine and valproic acid [VPA], have been frequently used in reprogramming of mouse and human somatic cells. This indicated that the reprogramming approaches related to these compounds were essential. These approaches were mainly divided into four classes: epigenetic modification, signal modulation, metabolic modulation and senescent suppression. The structures and functions of small molecules involved in these reprogramming approaches have been studied extensively. Molecular docking gave insights into the mechanisms and structural specificities of various small molecules in the epigenetic modification. The binding modes of RG108, Bix01294, tranylcypromine and VPA with their corresponding proteins clearly illustrated the interactions between these compounds and the active sites of the proteins. Glycogen synthase kinase 3β [CHIR99021], transforming growth factor β [616452, A83-01 and SB431542] and protein kinase A [forskolin] signaling pathway play important roles in signal modulation during reprogramming, however, the mechanisms and structural specificities of these inhibitors are still unknown. Further, the numbers of small molecules in the approaches of metabolic modulation and senescent suppression were too few to compare. This review aims to serve as a reference for reprogramming through small molecules in order to benefit future regenerative medicine and clinical drug discovery.

Stem cells are considered to have significant capacity to differentiate into various cell types in humans and animals. Unlike specialized cells, these cells can proliferate several times to produce millions of cells. Nowadays, pluripotent stem cells are important candidates to provide a renewable source for the replacement of cells in tissues of interest. The damage to neurons and glial cells in the brain or spinal cord is present in neurological disorders such as Amyotrophic lateral sclerosis, stroke, Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, Huntington’s disease, spinal cord injury, lysosomal storage disorder, epilepsy, and glioblastoma. Therefore, stem cell transplantation can be used as a novel therapeutic approach in cases of brain and spinal cord damage. Recently, researchers have generated neuron-like cells and glial-like cells from embryonic stem cells, mesenchymal stem cells, and neural stem cells. In addition, several experimental studies have been performed for developing stem cell transplantation in brain tissue. Herein, we focus on stem cell therapy to regenerate injured tissue resulting from neurological diseases and then discuss possible differentiation pathways of stem cells to the renewal of neurons.

Stem cell-based therapy is one of the therapeutic options with promising results in the treatment of diabetes. Stem cells from various sources are expanded and induced to generate the cells capable of secreting insulin. These insulin-producing cells [IPCs] could be used as an alternative to islets in the treatment of patients with diabetes. Soluble growth factors, small molecules, geneencoding transcription factors, and microRNAs [miRNAs] are commonly used for the induction of stem cell differentiation. MiRNAs are small non-coding RNAs with 21-23 nucleotides that are involved in the regulation of gene expression by targeting multiple mRNA targets. Studies have shown the dynamic expression of miRNAs during pancreatic development and stem cell differentiation. MiR- 7 and miR-375 are the most abundant miRNAs in pancreatic islet cells and play key roles in pancreatic development as well as islet cell functions. Some studies have tried to use these small RNAs for the induction of pancreatic differentiation. This review focuses on the miRNAs used in the induction of stem cells into IPCs and discusses their functions in pancreatic β-cells.

Tendon is a collagenous tissue to connect bone and muscle. Healing of damaged/injured tendon is the primary clinical challenge in musculoskeletal regeneration because they often react poorly to treatment. Tissue engineering (a triad strategy of scaffolds, cells and growth factors) may have the potential to improve the quality of tendon tissue healing under such impaired situations. Tendon tissue engineering aims to synthesize graft alternatives to repair the injured tendon. Biological scaffolds derived from decellularized tissue may be a better option as their biomechanical properties are similar to the native tissue. This review is designed to provide background information on the current challenges in curing torn/worn out the tendon and the clinical relevance of decellularized scaffolds for such applications.

Mesenchymal stem cell (MSC) therapy for clinical diseases associated with inflammation and tissue damage has become a progressive treatment strategy. MSCs have unique biological functions, such as homing, immune regulation, and differentiation capabilities, which provide the prerequisites for the treatment of clinical diseases. Oral diseases are often associated with abnormal immune regulation and epithelial tissue damage. In this review, we summarize previous studies that use MSC therapy to treat various oral inflammatory diseases, including oral ulceration, allergic diseases, chemo/radiotherapy-induced oral mucositis, periodontitis, osteonecrosis of the jaw, Sjögren's syndrome (SS), among other similar diseases. We highlight MSC treatment as a promising approach in the management of oral inflammatory diseases, and discuss the obstacles that remain and must be overcome for MSC treatment to thrive in the future.

Stem cells are undifferentiated cells with self-renewal property and varying differentiation potential that allow the regeneration of tissue cells of an organism throughout adult life beginning from embryonic development. Through the asymmetric cell divisions, each stem cell replicates itself and produces an offspring identical with the mother cell, and a daughter cell that possesses the characteristics of a progenitor cell and commits to a specific lineage to differentiate into tissue cells to maintain homeostasis. To maintain a pool of stem cells to ensure tissue regeneration and homeostasis, it is important to regulate the metabolic functioning of stem cells, progenitor cells and adult tissue stem cells that will meet their internal and external needs. Upon fertilization, the zygote transforms metabolic reprogramming while implantation, embryonic development, organogenesis processes and after birth through adult life. Metabolism in stem cells is a concept that is relatively new to be enlightened. There are no adequate and comprehensive in vitro studies on the comparative analysis of the effects of one-carbon (1-C) metabolism on fetal and adult stem cells compared to embryonic and cancer stem cells’ studies that have been reported recently. Since 1-C metabolism is linking parental environmental/ dietary factors and fetal development, investigating the epigenetic, genetic, metabolic and developmental effects on adult period is necessary. Several mutations and abnormalities in 1-C metabolism have been noted in disease changing from diabetes, cancer, pregnancy-related outcomes such as pre-eclampsia, spontaneous abortion, placental abruption, premature delivery, and cardiovascular diseases. In this review, the effects of 1-C metabolism, mainly the methionine and folate metabolism, in stem cells that exist in different developmental stages will be discussed.

The world is currently engulfed with a viral disease with no cure. Thus, far, millions of people are infected with the virus across the length and breadth of the world, with thousands losing their lives each passing day. The WHO in February 2020 classified the virus as a coronavirus and the name Coronavirus-19 (CoV-19) was offered to the virus. The disease caused by the virus was termed coronavirus disease-19 (COVID-19). The pathogenesis of COVID-19 is associated with elevation of several immune players as well as inflammatory factors which contribute to cytokine storms. Currently, the detection of CoV-19 RNA is through reverse transcriptase-polymerase chain reaction (RTPCR). Mesenchymal stem cells (MSCs) are capable of suppressing several kinds of cytokines via the paracrine secretion system. Therefore, MSCs therapy could be game changer in the treatment of the current COVID-19 pandemic. Moreover, intravenous IG may be capable of suppressing the high expression of IL-6 by the CoV-19 resulting in lessen disease burden. Anti-inflammatory medications like, corticosteroids, tocilizumab, glycyrrhetinic acid, as well as etoposide may be very advantageous in decreasing the COVID-19 burden because their mode of action targets the cytokine storms initiated by the CoV-19. It is important to indicate that, these medications do not target the virus itself. Therefore, potent CoV-19 anti-viral medications are needed to completely cure patients with COVID-19. Furthermore, a vaccine is urgently needed to stop the spread of the virus. This review, therefore, elucidates the immune players in the management of COVID-19; focusing principally on MSCs and inflammatory mediators.

Advances in single-cell technology and genetic mouse models have resulted in the identification of new types of hemopoietic stem cells (HSC), resulting in baffling observations, suggesting a reconsideration of the long-held notion that all hematopoietic cells in the adult are derived from HSCs. The existence of long-lived HSC-independent hematopoiesis has led to the conclusion that despite the single hierarchical differentiation route that generates functional blood types, other differentiation routes exist in-vivo. Heterogeneity in the HSC population and the evolving knowledge around HSC has translated to it’s improved application as a therapeutic tool for various blood disorders. The reprogramming of non-hematopoietic somatic and mature blood cells to pluripotency with their subsequent differentiation into hematopoietic stem cells/progenitor cells and the introduction of new generation sequencing holds the potential for the resolution of ambiguities involved in HSC bone marrow transplantation. There is a change in the paradigm for HSC transplantation donor selection. Donor choice favors haploidentical HCT than cord blood. This review provides a general overview of the current events around hemopoietic stem cells, with emphasis on the rising trend of HSC transplantation, especially haploidentical stem cell transplantation.

Currently, combining stem cells (SCs) with biomaterial scaffolds provides a promising strategy for the future of biomedicine and regenerative medicine (RG). The cells need similar substrates of the extracellular matrix (ECM) for normal tissue development, which signifies the importance of three dimensional (3D) scaffolds to determine cell fate. Herein, the importance and positive contributions of corresponding 3D scaffolds on cell functions, including cell interactions, cell migrations, and nutrient delivery, are presented. Furthermore, the synthesis techniques which are recruited to fabricate the 3D scaffolds are discussed, and the related studies of 3D scaffold for different tissues are also reported in this paper. This review focuses on 3D scaffolds that have been used for tissue engineering purposes and directing stem cell fate as a means of producing replacements for biomedical applications.