Abstract:Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been… Show more
“…In addition, we found that the ACC and MECA samples had a higher proportion of stem cells and myoepithelial cells (Wilcoxon Rank Sum p -value < 0.001), whereas the SDC and MEC samples exhibited abundant fibroblasts, dendritic cells (DCs), and ductal/basal epithelial cells (Wilcoxon Rank Sum p -value < 0.001). These results are consistent with the known cellular compositions of ID (higher rate of cellular division and stem cell properties) and ED (higher number of professional antigen-presenting cells (APCs)) 30 – 34 . Fig.…”
Gene expression analysis enhances proper cancer subtyping, a better understanding of the molecular characteristics of cancer, and strategies for precision medicine. However, salivary gland cancer (SGC) subtyping remains largely unexplored because of its rarity and diverse histopathological and immunological characteristics. This study aimed to determine whether the histological origin and immunological characteristics of SGC subtypes are intrinsic tumor immunity factors. We performed immune profiling of 94 RNA-seq of SGC tissues and found that the SGCs that originated from the excretory duct (ED), such as the salivary duct and mucoepidermoid carcinomas, exhibit higher immunity than those from the intercalated duct (ID), such as the adenoid cystic and myoepithelial carcinomas, based on the computationally predicted immune score (p < 0.001), immune cell enrichment in the tumor immune microenvironment (TIME) (p < 0.001), T-cell receptor diversity (p < 0.001), and expression of signal I (major histocompatibility complex, MHC, p < 0.001) and signal II (co-stimulatory, p < 0.001 and co-inhibitory, p < 0.001) genes. Further analysis revealed that tolerogenic dendritic cell-induced dysfunctional T-cell populations and T-cell exclusion in the TIME are the major immune evasive mechanisms of the ED-and ID-derived SGCs, respectively.
“…In addition, we found that the ACC and MECA samples had a higher proportion of stem cells and myoepithelial cells (Wilcoxon Rank Sum p -value < 0.001), whereas the SDC and MEC samples exhibited abundant fibroblasts, dendritic cells (DCs), and ductal/basal epithelial cells (Wilcoxon Rank Sum p -value < 0.001). These results are consistent with the known cellular compositions of ID (higher rate of cellular division and stem cell properties) and ED (higher number of professional antigen-presenting cells (APCs)) 30 – 34 . Fig.…”
Gene expression analysis enhances proper cancer subtyping, a better understanding of the molecular characteristics of cancer, and strategies for precision medicine. However, salivary gland cancer (SGC) subtyping remains largely unexplored because of its rarity and diverse histopathological and immunological characteristics. This study aimed to determine whether the histological origin and immunological characteristics of SGC subtypes are intrinsic tumor immunity factors. We performed immune profiling of 94 RNA-seq of SGC tissues and found that the SGCs that originated from the excretory duct (ED), such as the salivary duct and mucoepidermoid carcinomas, exhibit higher immunity than those from the intercalated duct (ID), such as the adenoid cystic and myoepithelial carcinomas, based on the computationally predicted immune score (p < 0.001), immune cell enrichment in the tumor immune microenvironment (TIME) (p < 0.001), T-cell receptor diversity (p < 0.001), and expression of signal I (major histocompatibility complex, MHC, p < 0.001) and signal II (co-stimulatory, p < 0.001 and co-inhibitory, p < 0.001) genes. Further analysis revealed that tolerogenic dendritic cell-induced dysfunctional T-cell populations and T-cell exclusion in the TIME are the major immune evasive mechanisms of the ED-and ID-derived SGCs, respectively.
“…The final goal of differentiating SG cells is to provide a cure for xerostomia patients. There have been clinical trials of allogeneic MSC transplantation, but they showed only short-term effect and could not repair damaged cells in the long term [6]. A possible reason would be immune rejection of MSC [25].…”
Section: Application and Limitationmentioning
confidence: 99%
“…Stem cell-based approaches hold great promise for SG regeneration due to their unique ability to differentiate into various cell types and promote tissue repair. Previous animal studies on engrafting mesenchymal stromal cells (MSCs) into damaged SG showed increased salivary flow rate and SG mass [6]. Meanwhile, Lin et al (2011) [7] have shown a more desirable effect using MSC-derived acinar-like cells for treatment compared to using MSC directly.…”
Salivary gland dysfunction significantly affects oral health and the quality of life, necessitating the development of effective regenerative therapies. In recent years, in vitro stem cell differentiation has emerged as a promising approach for salivary gland regeneration. This review provides a comprehensive overview of the current state of research in this field and discusses various types of stem cells, differentiation protocols, and the challenges and opportunities for translation to clinical practice. Additionally, we explore the potential of stem cell-based therapies which may revolutionize salivary gland regeneration and improve patient outcomes in the future.
“…This groundbreaking work marks the first instance of salivary gland rescue using salispheres and the first clear demonstration of salivary gland stem/progenitor cell self-renewal and multilineage differentiation into functional organoids. MSCs are multipotent adult stem cells that can differentiate into several cell types, including adipocytes [184], osteoblasts [185], chondrocytes [186], myocytes [187], cardiomyocytes [188], hepatocytes [189], neuronal cells [190], and salivary gland cells [191], among others. MSCs exhibit anti-inflammatory, anti-fibrotic, and regenerative potential [192,193].…”
Salivary gland dysfunction affects millions globally, and tissue engineering may provide a promising therapeutic avenue. This review delves into the current state of salivary gland tissue engineering research, starting with a study of normal salivary gland development and function. It discusses the impact of fibrosis and cellular senescence on salivary gland pathologies. A diverse range of cells suitable for tissue engineering including cell lines, primary salivary gland cells, and stem cells are examined. Moreover, the paper explores various supportive biomaterials and scaffold fabrication methodologies that enhance salivary gland cell survival, differentiation, and engraftment. Innovative engineering strategies for the improvement of vascularization, innervation, and engraftment of engineered salivary gland tissue, including bioprinting, microfluidic hydrogels, mesh electronics, and nanoparticles, are also evaluated. This review underscores the promising potential of this research field for the treatment of salivary gland dysfunction and suggests directions for future exploration.
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