Current Stem Cell Research & Therapy - Volume 17, Issue 6, 2022

Mesenchymal stem cells (MSCs) are remarkable and noteworthy. Identification of markers for MSCs enables the study of their niche in vivo. It has been identified that glioma-associated oncogene 1 positive (Gli1+) cells are mesenchymal stem cells supporting homeostasis and injury repair, especially in the skeletal system and teeth. This review outlines the role of Gli1+ cells as MSC subpopulation in both bones and teeth, suggesting the prospects of Gli1 an + cells in stem cell- based tissue engineering.

Tendons are connective tissue structures of paramount importance to the human ability of locomotion. Tendinopathy and tendon rupture can be resistant to treatment and often recurs, thus resulting in a significant health problem with a relevant social impact worldwide. Unfortunately, existing treatment approaches are suboptimal. A better understanding of the basic biology of tendons may provide a better way to solve these problems and promote tendon regeneration. Stem cells, either obtained from tendons or non-tendon sources, such as bone marrow (BMSCs), adipose tissue (AMSCs), as well as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have received increasing attention toward enhancing tendon healing. There are many studies showing that stem cells can contribute to improving tendon healing. Hence, in this review, the current knowledge of BMSCs, AMSCs, TSPCs, ESCs, and iPSCs for tendon regeneration, as well as the advantages and limitations among them, has been highlighted. Moreover, the transcriptional and bioactive factors governing tendon healing processes have been discussed.

Natural Killer (NK) cells were initially described in the early 1970s as major histocompatibility complex unrestricted killers due to their ability to spontaneously kill certain tumor cells. In the past decade, the field of NK cell-based treatment has been accelerating exponentially, holding a dominant position in cancer immunotherapy innovation. Generally, research on NK cell-mediated antitumor therapies can be categorized into three areas: choosing the optimal source of allogeneic NK cells to yield massively amplified “off-the-shelf” products, improving NK cell cytotoxicity and longevity, and engineering NK cells with the ability of tumor-specific recognition. In this review, we focused on NK cell manufacturing techniques, some auxiliary methods to enhance the therapeutic efficacy of NK cells, chimeric antigen receptor NK cells, and monoclonal antibodies targeting inhibitory receptors, which can significantly augment the antitumor activity of NK cells. Notably, emerging evidence suggests that NK cells are a promising constituent of multipronged therapeutic strategies, strengthening immune responses to cancer.

Stem cells from human exfoliated deciduous teeth (SHEDs) are relatively easy to isolate from exfoliated deciduous teeth, which are obtained via dental therapy as biological waste. SHEDs originate from the embryonic neural crest, and therefore, have considerable potential for neurogenic differentiation. Currently, an increasing amount of research is focused on the therapeutic applications of SHEDs in neurological diseases and injuries. In this article, we summarize the biological characteristics of SHEDs and the potential role of SHEDs and their derivatives, including conditioned medium from SHEDs and the exosomes they secrete, in the prevention and treatment of neurological diseases and injuries.

Despite the plethora of literature regarding isolation and characterization of periodontal ligament stem cells (PDLSCs), due to the existence of controversies in the results, in this comprehensive review, we aimed to summarize and compare the effect of isolation methods on PDLSC properties, including clonogenicity, viability/proliferation, markers expression, cell morphology, differentiation, and regeneration. Moreover, the outcomes of included studies, considering various parameters, such as teeth developmental stages, donor age, periodontal ligament health status, and part of the teeth root from which PDLSCs were derived, have been systematically discussed. It has been shown that from included studies, PDLSCs can be isolated from teeth at any developmental stages, health status condition, and donor age. Furthermore, a non-enzymatic digestion method, named as an explant or outgrowth technique, is a suitable protocol for PDLSCs isolation.

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) remains a serious clinical problem but has no approved pharmacotherapy. Mesenchymal stem cells (MSCs) represent an attractive therapeutic tool for tissue damage and inflammation owing to their unique immunomodulatory properties. The present study aims to explore the therapeutic effect and underlying mechanisms of human umbilical cord MSCs (UC-MSCs) in ALI mice. Objective: In this study, we identify a novel mechanism for human umbilical cord-derived MSCs (UC-MSCs)-mediated immunomodulation through PGE2-dependent reprogramming of host macrophages to promote their PD-L1 expression. Our study suggests that UC-MSCs or primed- UC-MSCs offer new therapeutic approaches for lung inflammatory diseases. Methods: Lipopolysaccharide (LPS)-induced ALI mice were injected with 5×10⁵ UC-MSCs via the tail vein after 4 hours of LPS exposure. After 24 hours of UC-MSC administration, the total protein concentration and cell number in the bronchoalveolar lavage fluid (BALF) and cytokine levels in the lung tissue were measured. Lung pathological changes and macrophage infiltration after UCMSC treatment were analyzed. Moreover, in vitro co-culture experiments were performed to analyze cytokine levels of RAW264.7 cells and Jurkat T cells. Results: UC-MSC treatment significantly improved LPS-induced ALI, as indicated by decreased total protein exudation concentration and cell number in BALF and reduced pathological damage in ALI mice. UC-MSCs could inhibit pro-inflammatory cytokine levels (IL-1β, TNF-α, MCP-1, IL-2, and IFN-γ), while enhancing anti-inflammatory cytokine IL-10 expression, as well as reducing macrophage infiltration into the injured lung tissue. Importantly, UC-MSC administration increased programmed cell death protein ligand 1 (PD-L1) expression in the lung macrophages. Mechanistically, UC-MSCs upregulated cyclooxygenase-2 (COX2) expression and prostaglandin E2 (PGE2) secretion in response to LPS stimulation. UC-MSCs reduced the inflammatory cytokine levels in murine macrophage Raw264.7 through the COX2/PGE2 axis. Furthermore, UC-MSC- derived PGE2 enhanced PD-L1 expression in RAW264.7 cells, which in turn promoted programmed cell death protein 1 (PD-1) expression and reduced IL-2 and IFN-γ production in Jurkat T cells. Conclusion: Our results suggest that UC-MSCs attenuate ALI via PGE2-dependent reprogramming of macrophages to promote their PD-L1 expression.

Aim: The aim of this study was to compare dental pulp tissue in human exfoliated deciduous teeth (SHEDs) and dental pulp stem cells (DPSCs) in response to ascorbic acid as the sole osteoblast inducer. Background: A cocktail of ascorbic acid, β-glycerophosphate, and dexamethasone has been widely used to induce osteoblast differentiation. However, under certain conditions, β-glycerophosphate and dexamethasone can cause a decrease in cell viability in stem cells. Objectives: This study aims to determine the cytotoxic effect and potential of ascorbic acid as the sole inducer of osteoblast differentiation. Methods: Cytotoxicity analyses in the presence of 10-500 μg/mL ascorbic acid were performed in both cell types using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The concentrations below the IC50 (i.e., 10-150 μg/mL) were used to determine osteoblast differentiation potential of ascorbic acid using the alkaline phosphatase (ALP) assay, von Kossa staining, and reverse transcription-polymerase chain reaction. Results: SHEDs and DPSCs proliferated for 21 days, expressed a Mesenchymal Stem Cell (MSC) marker (CD73+), and did not express Hematopoietic Stem Cell (HSC) markers (CD34- and SLAMF1-). SHEDs had a higher range of IC50 values (215-240 μg/mL ascorbic acid), while the IC50 values for DPSCs were 177-211 μg/mL after 24-72 hours. SHEDs treated with 10-100 μg/mL ascorbic acid alone exhibited higher ALP-specific activity and a higher percentage of mineralisation than DPSCs. Both cell types expressed osteoblast markers on day 21, i.e., RUNX2+ and BSP+, in the presence of ascorbic acid. Conclusions: SHEDs survive at higher concentrations of ascorbic acid as compared to DPSC. The cytotoxic effect was only exhibited at ≥250 μg/mL ascorbic acid. In addition, SHED exhibited better ALP and mineralization activities, but lower osteoblast marker expression than DPSC in response to ascorbic acid as the sole inducer.