Generation of Hypoparathyroid Rats <em>via</em> Carbon-Nanoparticle-Assisted Parathyroidectomy

Hypoparathyroidism (HypoPT) is a rare disease involving the parathyroid glands that is characterized by a reduced secretion or potency of the parathyroid ...

Sichuan University

The radiation-induced bystander effect (RIBE) is a destructive reaction in nonirradiated cells and is one primary factor in determining the efficacy and success of radiation therapy in the field of cancer treatment. Previously reported studies have shown that the RIBE can be mediated by exosomes that carry miRNA components within. Exosomes, which are one type of cell-derived vesicle, exist in different biological conditions and serve as an important additional pathway for signal exchange between cells. In addition, exosome-derived miRNAs are confirmed to play an important role in RIBE, activating the bystander effect and genomic instability after radiotherapy. After investigating the field of RIBE, it is important to understand the mechanisms and consequences of biological effects as well as the role of exosomes and exosomal miRNAs therein, from different sources and under different circumstances, respectively. More discoveries could help to establish early interventions against RIBE while improving the efficacy of radiotherapy. Meanwhile, measures that would alleviate or even inhibit RIBE to some extent may exist in the near future.

Radiation-Induced Bystander Effect can be Transmitted Through Exosomes Using miRNAs as Effector Molecules.

Ionizing radiation (IR)-induced vascular disorders slow down tissue regeneration. Exosomes derived from plasma exhibit potential to promote angiogenesis; meanwhile, the immune microenvironment plays a significant role in the process. This study aimed to test the hypothesis that plasma exosomes promote angiogenesis in irradiated tissue by mediating the immune microenvironment. First, we explored the impact of IR on macrophages. We found that cell viability and capacity for promoting angiogenesis were decreased in irradiated macrophages compared to control macrophages. Then, we isolated and characterized rat plasma-derived exosomes (RP-Exos) which were defined as 40-160 nm extracellular vesicles extracted from rat plasma. Afterward, we evaluated the effects of RP-Exos on the behaviors of irradiated macrophages. Our results show that RP-Exos promoted cell proliferation. More importantly, we found that RP-Exos stimulated the immune microenvironment in a manner that improved the angiogenesis-related genes and proteins of irradiated macrophages. The supernatant of macrophage cell cultures was used as conditioned medium to treat human primary umbilical vein endothelial cells, further confirming the pro-angiogenic ability of macrophages receiving RP-Exo intervention. RP-Exos were used in vivo to treat irradiated skin or calvarial defects in irradiated Sprague-Dawley male rats. The results indicated the ability of RP-Exos to enhance angiogenesis and promote tissue regeneration. Our research suggested the potential of plasma exosomes to be used as immunomodulatory agents with angiogenic capacity to treat radiation-associated vascular disorders and facilitate tissue repair.

Exosomes derived from plasma: promising immunomodulatory agents for promoting angiogenesis to treat radiation-induced vascular dysfunction.

Temporomandibular disorders (TMD) are diseases involving the temporomandibular joint (TMJ), masticatory muscles, and osseous components. TMD has a high prevalence, with an estimated 4.8% of the U.S. population experiencing signs and symptoms, and represents a financial burden to both individuals and society. During TMD progression, the most frequently affected site is the condylar cartilage. Comprising both fibrous and cartilaginous tissues, condylar cartilage has restricted cell numbers but lacks a vascular supply and has limited regenerative properties. In 2016, a novel stem cell niche containing a reservoir of fibrocartilage stem cells (FCSCs) was discovered in the condylar cartilage of rats. Subsequently, FCSCs were identified in mouse, rabbit, and human condylar cartilage. Unlike mesenchymal stem cells or other tissue-specific stem/progenitor cells, FCSCs play a unique role in the development and regeneration of fibrocartilage. More importantly, engraftment treatment of FCSCs has been successfully applied in animal models of TMD. In this context, FCSCs play a major role in the regeneration of newly formed cartilage. Furthermore, FCSCs participate in the regeneration of intramembranous bone by interacting with endothelial cells in bone defects. This evidence highlights the potential of FCSCs as an ideal stem cell source for the regeneration of oral maxillofacial tissue. This review is intended to detail the current knowledge of the characteristics and function of FCSCs in the TMJ, as well as the potential therapeutic applications of FCSCs. A deep understanding of the properties of FCSCs can thus inform the development of promising, biologically based strategies for TMD in the future.

Fibrocartilage Stem Cells in the Temporomandibular Joint: Insights From Animal and Human Studies.

Dental follicle progenitor/stem cells (DFPCs) are a group of dental mesenchyme stem cells that lie in the dental follicle and play a critical role in tooth development and maintaining function. Originating from neural crest, DFPCs harbor a multipotential differentiation capacity. More importantly, they have superiorities, including the easy accessibility and abundant sources, active self-renewal ability and noncontroversial sources compared with other stem cells, making them an attractive candidate in the field of tissue engineering. Recent advances highlight the excellent properties of DFPCs in regeneration of orofacial tissues, including alveolar bone repair, periodontium regeneration and bio-root complex formation. Furthermore, they play a unique role in maintaining a favorable microenvironment for stem cells, immunomodulation and nervous related tissue regeneration. This review is intended to summarize the current knowledge of DFPCs, including their stem cell properties, physiological functions and clinical application potential. A deep understanding of DFPCs can thus inspire novel perspectives in regenerative medicine in the future.

Function of Dental Follicle Progenitor/Stem Cells and Their Potential in Regenerative Medicine: From Mechanisms to Applications.

Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) are two peptides that regulate mineral ion homeostasis, skeletal development, and bone turnover by activating parathyroid hormone 1 receptor (PTH1R). PTH1R signaling is of profound clinical interest for its potential to stimulate bone formation and regeneration. Recent pre-clinical animal studies and clinical trials have investigated the effects of PTH and PTHrP analogs in the orofacial region. Dental mesenchymal stem cells (MSCs) are targets of PTH1R signaling and have long been known as major factors in tissue repair and regeneration. Previous studies have begun to reveal important roles for PTH1R signaling in modulating the proliferation and differentiation of MSCs in the orofacial region. A better understanding of the molecular networks and underlying mechanisms for modulating MSCs in dental diseases will pave the way for the therapeutic applications of PTH and PTHrP in the future. Here we review recent studies involving dental MSCs, focusing on relationships with PTH1R. We also summarize recent basic and clinical observations of PTH and PTHrP treatment to help understand their use in MSCs-based dental and bone regeneration.

Parathyroid Hormone 1 Receptor Signaling in Dental Mesenchymal Stem Cells: Basic and Clinical Implications.

Resulting from bacterial infection, apical periodontitis (AP) is a common inflammatory disease of the periapical region of the tooth. The regeneration of the destroyed periapical alveolar bone and the surrounding periodontium tissues has long been a difficult task in clinical practice. These lesions are closely related to pathogen invasion and an overreactive immune response. It is worth noting that the protective healing process occurs simultaneously, in which mesenchymal stem cells (MSCs) have a crucial function in mediating the immune system and promoting regeneration. Here, we review the recent studies related to AP, with a focus on the regulatory network of MSCs. We also discuss the potential therapeutic approaches of MSCs in inflammatory diseases to provide a basis for promoting tissue regeneration and modulating inflammation in AP. A deeper understanding of the protective action of MSCs and the regulatory networks will help to delineate the underlying mechanisms of AP and pave the way for stem-cell-based regenerative medicine in the future.

Protective Actions in Apical Periodontitis: The Regenerative Bioactivities Led by Mesenchymal Stem Cells.

Pulpal and periapical diseases are the most common dental diseases. The traditional treatment is root canal therapy, which achieves satisfactory therapeutic outcomes-especially for mature permanent teeth. Apexification, pulpotomy, and pulp revascularization are common techniques used for immature permanent teeth to accelerate the development of the root. However, there are obstacles to achieving functional pulp regeneration. Recently, two methods have been proposed based on tissue engineering: stem cell transplantation, and cell homing. One of the goals of functional pulp regeneration is to achieve innervation. Nerves play a vital role in dentin formation, nutrition, sensation, and defense in the pulp. Successful neural regeneration faces tough challenges in both animal studies and clinical trials. Investigation of the regeneration and repair of the nerves in the pulp has become a serious undertaking. In this review, we summarize the current understanding of the key stem cells, signaling molecules, and biomaterials that could promote neural regeneration as part of pulp regeneration. We also discuss the challenges in preclinical or clinical neural regeneration applications to guide deep research in the future.

Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends.

Oral inflammatory diseases such as apical periodontitis are common bacterial infectious diseases that may affect the periapical alveolar bone tissues. A protective process occurs simultaneously with the inflammatory tissue destruction, in which mesenchymal stem cells (MSCs) play a primary role. However, a systematic and precise description of the cellular and molecular composition of the microenvironment of bone affected by inflammation is lacking. In this study, we created a single-cell atlas of cell populations that compose alveolar bone in healthy and inflammatory disease states. We investigated changes in expression frequency and patterns related to apical periodontitis, as well as the interactions between MSCs and immunocytes. Our results highlight an enhanced self-supporting network and osteogenic potential within MSCs during apical periodontitis-associated inflammation. MSCs not only differentiated toward osteoblast lineage cells but also expressed higher levels of osteogenic-related markers, including Sparc and Col1a1. This was confirmed by lineage tracing in transgenic mouse models and human samples from oral inflammatory-related alveolar bone lesions. In summary, the current study provides an in-depth description of the microenvironment of MSCs and immunocytes in both healthy and disease states. We also identified key apical periodontitis-associated MSC subclusters and their biomarkers, which could further our understanding of the protective process and the underlying mechanisms of oral inflammatory-related bone disease. Taken together, these results enhance our understanding of heterogeneity and cellular interactions of alveolar bone cells under pathogenic and inflammatory conditions. We provide these data as a tool for investigators not only to better appreciate the repertoire of progenitors that are stress responsive but importantly to help design new therapeutic targets to restore bone lesions caused by apical periodontitis and other inflammatory-related bone diseases.

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling.

The biological characteristics of the temporomandibular joint disc involve complex cellular network in cell identity and extracellular matrix composition to modulate jaw function. The lack of a detailed characterization of the network severely limits the development of targeted therapies for temporomandibular joint-related diseases. Here we profiled single-cell transcriptomes of disc cells from mice at different postnatal stages, finding that the fibroblast population could be divided into chondrogenic and non-chondrogenic clusters. We also find that the resident mural cell population is the source of disc progenitors, characterized by ubiquitously active expression of the NOTCH3 and THY1 pathways. Lineage tracing reveals that Myh11 mural cells coordinate angiogenesis during disc injury but lost their progenitor characteristics and ultimately become Sfrp2 non-chondrogenic fibroblasts instead of Chad chondrogenic fibroblasts. Overall, we reveal multiple insights into the coordinated development of disc cells and are the first to describe the resident mural cell progenitor during disc injury.

A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury.

The utilization of lasers has been regarded as a novel technique for the purposes of clinical use in the dental field. Recently, numerous studies have been conducted on the potential applications of laser therapy in endodontics. Moreover, due to their ablation, penetrability, and disinfection capabilities, lasers have performed well with respect to endodontic treatments, including root canal treatment, vital pulp therapy (pulp capping and pulpotomy), dentinal hypersensitivity treatment, and management of dental pain related to pulp and periradicular disease. In particular, the superiorities of laser-aided pulp therapy are emphasized through condensed clinical controlled trials, and histological studies, in this review. Moreover, the ingenious use of laser applications with respect to aiding in the acceleration of root development and the extraction of foreign matters (i.e., broken files and fiber posts) in canals has quickly become the cutting-edge trend of current research. This review offers a summary and discussion of the current literature on all the aforementioned laser applications. Moreover, the characteristics of laser devices, including erbium lasers, neodymium-doped lasers, CO lasers, and diode lasers, are detailed and discussed here, providing useful references for laser application in endodontics. We also focus on the different wavelengths with respect to the lasers that are applied in endodontics. High-power lasers perform well as operative instruments; in addition, low-level lasers lead to the regulation of pulp inflammation, and the promotion of pulp healing. This narrative review provides a summary of the advanced applications of lasers in conjunction with various devices in the practice of endodontics, and aims to inspire innovative perspectives on lasers in the context of the treatment of dental diseases, especially pulp diseases, in the future.

Ping Lyu

Sichuan University

Generation of Hypoparathyroid Rats via Carbon-Nanoparticle-Assisted Parathyroidectomy