Current Stem Cell Research & Therapy - Volume 16, Issue 5, 2021

Background: Mesenchymal Stromal Cells (MSC) have the potential for self-renewal and differentiation in different tissues, characteristics that encourage their use in regenerative medicine. Dental tissue MSCs are easy to collect, have the same embryonic origin as neurons and have neuronal markers that allow their use in treating neurodegenerative diseases. Human Exfoliated Deciduous teeth (SHED)-derived stromal cells are considered immature and present positive expression of pluripotency and neuronal markers. Studies have shown that after the induction of neuronal differentiation in vitro, SHED increased the expression of neuronal markers, such as βIIItubulin, nestin, GFAP, NeuN, and NFM, demonstrating the potential use of these cells in preclinical studies. The results of this review reflect the consensus that in diseases such as spinal cord injury, cerebral ischaemia, and Alzheimer’s and Parkinson’s disease, SHED could function in the suppression of the inflammatory response, neuroprotection, and neuronal replacement. Conclusion: For these cells to be used in large-scale clinical trials, standardization of the isolation techniques and theneuronal induction medium are necessary. The potential of SHED to induce neuronal differentiation is evident, demonstrating that this resource is promising and shows great potential for use in future preclinical and clinical trials of neurodegenerative diseases.

The current decade witnesses the regenerative potential of Stem Cells (SCs) based lifesaving therapies for the treatment of various disease conditions. Human teeth act as a reservoir for SCs that exist in high abundance in baby, wisdom, and permanent teeth. The collection of Stem cells from Human Exfoliated Deciduous teeth (SHED) is considered a simple process as it offers the convenience of little or no pain. In comparison to the SCs from dental or bone marrow or other tissues, the SHED offers the benefit of higher cellular differentiation and proliferation. Massive in vitro and in vivo studies reveal the regenerative potential of SHED in the engineering of the dental pulp tissue, neuronal tissue, root, bio root, cardiovascular tissues, lymphatic tissues, renal tissues, dermal tissues, hepatic tissues, and bone tissues. The current review describes the methods of collection/ isolation/storage, various biomarkers, and types of SHED. This review highlights the regenerative potential of SHED in the engineering of different tissues of the human body. As per the available research evidence, the present study supports that SHED may differentiate into the endothelial cells, neurons, odontoblasts, pancreatic β-cells, hepatocytes, renal cells, fibroblasts, osteoblasts, and many other types of cells. The present study recommends that further clinical trials are required before the clinical application of SHED-based therapies.

Stem cells from Human Exfoliated Deciduous teeth (SHED) are considered one of the most attractive cell sources for tissue engineering due to their easy acquisition with no donor morbidity, ready availability, ability to self-renew with high proliferation, capacity for multilineage differentiation and immunomodulatory functions. To date, SHED are able to differentiate into odonto-/ osteoblasts, neuronal cells, endothelial cells, hepatocyte-like cells, chondrocytes, epidermal cells among many other cell types. Accordingly, SHED possess a promising potential to be used in the cell-based therapy for various diseases, including reversible pulpitis, orofacial bone defects, neurodevelopmental disease and ischemic injury. Despite this potential, it has been a concern that tissue specific stem cells do not differentiate with the same efficacy into all the different lineages as they may have an inherent tendency to differentiate toward the tissues from which they were originally derived. Furthermore, stem cell niche comprises of a complex microenvironment where various cells, soluble signals, extracellular matrix and physical cues interplay to maintain the stemness of SHED and modulate their differentiation. Therefore, it is of significant importance to identify the specific microenvironmental cues that regulate lineage specific differentiation of SHED, which could inspire to develop functional approaches in target tissue regeneration. In this review, we highlight the recent studies that demonstrated multilineage differentiation capacity of SHED, focusing on how the microenvironment could be modified using different cues in order to achieve tissue specific regeneration.

Mesenchymal Stem Cells (MSCs) are adult stem cells that are gaining worldwide attention for their multi-potential use in tissue engineering-based regenerative medicine. They can be obtained from numerous sources and one of the excellent sources is the dental tissue, such as Stem cells that are extracted from the Human Exfoliated Deciduous teeth (SHED). SHED are considered ideal due to their inherent characteristics, including the capability to proliferate quickly with minimal oncogenesis risk, multipotency capacity and their ability to suppress the immune system. On top of these positive cell traits, SHED are easily accessible with the patient’s safety assured, posing less ethical issues and could also provide a sufficient number of cells for prospective clinical uses. This is primarily attributed to their ability to differentiate into multiple cell linages, including osteoblasts, odontoblasts, neuronal cells, adipocytes, as well as endothelial cells. Albeit SHED having a bright future, there still remains an obstacle to develop reliable experimental techniques to retain the long-term regeneration potential of the stem cells for prospective research and clinical applications. Therefore, this review aims to describe the various isolation, expansion and cryopreservation techniques used by researchers in this stem cell field. Optimization of these techniques is crucial to obtain distinct SHED culture with preserved stem cell properties, which enable more reproducible results that will be the key for further stem cell therapy development.

Stem cells can multiply into more cells with similar types in an undifferentiated form and differentiate into other types of cells. The great success and key essence of stem cell technology is the isolation of high-quality Mesenchymal Stem Cells (MSCs) with high potency, either with multipotent or pluripotent property. In this line, Stem cells from Human Exfoliated Deciduous teeth (SHEDs) are highly proliferative stem cells from dental pulp and have multipoint differentiation capacity. These cells play a pivotal role in regenerative medicine, such as cell repair associated with neurodegenerative, hepatobiliary, and pancreatic diseases. In addition, stem cell therapy has been widely used to regulate immune response and repair of tissue lesions. This overview captured the differential biological characteristics, and the potential role of stem cell technology and paid special attention to human welfare SHEDs in eliminating the above-mentioned diseases. This review provides further insights into stem cell technology by expanding the therapeutic potential of SHEDs in tissue engineering and cell organ repairs.

The concept of regenerative endodontics wherein one can replace damaged pulp structures and recuperate the functionality in erstwhile necrotic and infected root canal systems has been a cutting-edge technology. Though the notion started as early as the 1960s, even before the discovery of stem cells and regenerative medicine, it was in the 2000s that this procedure gained momentum. Ever since then, researchers continue to discover its essential benefit to immature teeth and its ability to overcome the caveats of endodontic therapy, which is commonly known as root canal treatment. Further, through this therapy, one can redevelop root even in immature teeth with necrotic pulps, which overall helps in maintaining skeletal and dental development. Past literature indicates that regenerative endodontic procedures seem to be successful, especially when compared with other conventional techniques such as Mineral Trioxide Aggregate apexification. Besides, many clinicians have begun to apply regenerative endodontic procedures to mature teeth in adult patients, with several clinical case reports that have shown complete resolution of signs and symptoms of pulp necrosis. Generally, the three most desirable outcomes anticipated by clinicians from this procedure include resolution of clinical signs and symptoms, root maturation and redevelopment of the neurogenesis process. Despite this, whether these objectives and true regeneration of the pulp/dentin complex are achieved is still a question mark. Following the discovery that regenerative endodontics indeed is a stem cell-based treatment, addressing the fundamental issue surrounding stem cells might assist in achieving all identified clinical outcomes while favoring tissue formation that closely resembles the pulp-dentin complex.

Macrophage proliferation and skewed myelopoiesis-induced monocytosis, as well as neutrophils, enhance the generation of atherogenic inflammatory cells in a lesion area, leading to plaque formation and Cardiovascular Disease (CVD). Among all risk factors, accumulated data have shown that hyperlipidemia activates Hematopoietic Stem/Progenitor Cells (HSPCs) in the Bone Marrow (BM) niche. Recently, proliferation of Granulocyte-Monocyte Progenitors (GMPs) has been demonstrated to drive skewed myelopoiesis, while HSPCs remain quiescent. In this review, we discuss how HSPCs and GMPs participate in atherosclerosis of mice in terms of proliferation and cell mobilization from BM to peripheral blood and the lesion area. We also describe how the spleen, an extramedullary organ, is involved in skewed myelopoiesis and inflammation in atherosclerosis. We further summarize the clinical evidence of the relationship of HSPCs with coronary stenoses in patients with CVD. Ultimately, this review facilitates understanding the pathological roles of HSPCs and GMPs in atherosclerosis for future treatments.

The isolation and culture of murine Bone Marrow-derived Mesenchymal stromal Stem Cells (mBMSCs) have attracted great interest in terms of the pre-clinical applications of stem cells in tissue engineering and regenerative medicine. In addition, culturing mBMSCs is important for studying the molecular mechanisms of bone remodeling using relevant transgenic mice. Several factors have created challenges in the isolation and high-yield expansion of homogenous mBMSCs; these factors include low frequencies of Bone Marrow-derived mesenchymal stromal Stem Cells (BMSCs) in bone marrow, variation among inbred mouse strains, contamination with Haematopoietic Progenitor Cells (HPCs), the replicative senescence phenotype and cellular heterogeneity. In this review, we provide an overview of nearly all protocols used for isolating and culturing mBMSCs with the aim of clarifying the most important guidelines for culturing highly purified mBMSC populations retaining in vitro and in vivo differentiation potential.

The prevalence of Heart Failure (HF) has increased over time. Ischemic heart failure accounts for 50% of HF, which results from ischemic coronary heart diseases such as Myocardial Infarction (MI). Conventionally, reduction of cardiac load and revascularization partially increase cardiomyocyte survival and preserve cardiac functions. Nevertheless, how to improve cardiomyocyte rescue and prevent HF progression remain as challenges. Mesenchymal Stem Cells (MSCs) are multipotent stem cells that give rise to various lineages. The administration of MSCs promotes cardiomyocyte survival and improves cardiac functions in animal models of MI and patients with ischemic cardiomyopathy. However, after injection, MSCs persist for a very short time, indicating that the prolonged protective effects of MSCs on cardiomyocytes may be mediated by paracrine functions of MSCs, such as exosomes. In this review, we focus on MSC-derived exosomes in cardiomyocyte protection to facilitate future applications of exosomes in HF treatment.

Infertility is defined as not being able to become pregnant or to conceive a child after one year or longer of regular unprotected intercourse. Male infertility refers to a male’s inability to cause pregnancy that can result from deficiencies in semen quality, sperm concentration, or abnormal sperm function. Till now, there are few effective methods for the treatment of a couple with male infertility. In the past few years, stem cell-based therapy as a promising strategy has emerged for the treatment of male infertility. Human Pluripotent Stem Cells (hPSCs) can self-renew and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) and induced Pluripotent Stem Cells (hiPSCs) are two pluripotent populations that can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. Both undifferentiated hiPSCs and hESCs are powerful candidates for the treatment of male infertility. Generation of male germ cells from hPSCs can provide new mechanistic insights into the regulation of spermatogenesis and have a great opportunity for families with infertility. Therefore, a robust, reproducible, and low-cost culture method that supports hPSCs differentiation into male germ cells is necessary. However, very few studies have focused on the derivation of sperm-like cells from hiPSCs and the details of hPSCs differentiation into male germ cells have not been fully investigated. Therefore, in this review, we focus on the in vitro differentiation potential of hiPSCs into male germ cells.

Background: Accumulating evidence has revealed the important role of Cancer Stem Cells (CSCs) in driving tumor initiation and tumor relapse or metastasis. Therapeutic strategies that selectively target CSCs may be effective approaches to eliminate cancer. Salinomycin, an antitumor agent, was identified as a selective inhibitor of several types of CSCs. We previously reported that salinomycin inhibits the migration and invasiveness of Liver Cancer Stem Cells (LCSCs). Objective: This study was conducted to explore the role of salinomycin in suppressing the stemness properties of LCSCs and the mechanism. Methods: LCSCs were identified and enriched from MHCC97H cells. Salinomycin was used to treat LCSCs at the indicated concentrations. Sphere formation ability, chemotherapy resistance, expression of CSC surface markers, Young’s modulus and tumorigenicity of LCSCs were assessed to evaluate the effect of salionmycin on LCSCs. The expression of β-catenin was evaluated by western blotting. LiCl was used to activate the Wnt/β-catenin signaling pathway. Results: Salinomycin suppresses the stemness properties of LCSCs. Moreover, salinomycin could also inhibit the activation of Wnt/β-catenin signaling in LCSCs. Nevertheless, the stemness properties of LCSCs could be recovered when Wnt/β-catenin signaling was activated by LiCl. Further studies demonstrated that salinomycin also significantly reduces the tumorigenicity of LCSCs in vivo by suppressing the Wnt/β-catenin signaling pathway. Conclusion: Salinomycin could suppress stemness properties and induce differentiation of LCSCs through the Wnt/β-catenin signaling pathway, which provides evidence that salinomycin may serve as a potential drug for liver cancer therapy targeting LCSCs in the clinic.