Abstract:Background
Current treatments for salivary gland (SG) hypofunction are palliative and do not address the underlying cause or progression of the disease. SG-derived stem cells have the potential to treat SG hypofunction, but their isolation is challenging, especially when the tissue has been damaged by disease or irradiation for head and neck cancer. In the current study, we test the hypothesis that multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model are capable of tr… Show more
“…3 suggest that only cells that formed aggregates during culture with SMG-ECM expressed markers of the SG epithelial cell phenotype. 221 Fig. 3 Ultrastructural characteristics of rat SMG tissue and SMG-ECM-treated aggregates were remarkably similar.…”
Section: Autologous Multipotent Mscs As a Potential New Therapeutic P...mentioning
confidence: 77%
“… 163 More recently, we prepared ECM from decellularized rat SMG tissue, and investigated whether this matrix can direct the trans-differentiation of autologous BM-MSCs to the SG epithelial cell lineage in vitro. 221 We found that culture of BM-MSCs with homogenates of SMG-ECM for 14 days induced the formation of aggregates that expressed SG-specific epithelial cell lineage markers (AQP5, MUC10, KRT14, MIST1) and acinar-associated tight junction proteins (CLDN3 and CLDN10). In addition, the accumulation of glycoprotein/mucin, shown by PAS staining, correlated with the appearance on transmission electron micrographs (TEM) of tight junctions, secretory granule-like structures, and peripheral nuclei, suggesting that the cells were capable of functions associated with differentiated SG cells.…”
Section: Autologous Multipotent Mscs As a Potential New Therapeutic P...mentioning
confidence: 84%
“…Scale bar is shown in each panel. Images were selected from original work published by BioMed Central in Tran et al 221 …”
Section: Autologous Multipotent Mscs As a Potential New Therapeutic P...mentioning
confidence: 99%
“…Scale bar for SMG tissue = 50 µm; scale bar for aggregates implanted for 30 days = 20 µm. Images were selected from original work published by BioMed Central in Tran et al 221 …”
Section: Autologous Multipotent Mscs As a Potential New Therapeutic P...mentioning
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 suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the “immuno-privileged” status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient’s immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.
“…3 suggest that only cells that formed aggregates during culture with SMG-ECM expressed markers of the SG epithelial cell phenotype. 221 Fig. 3 Ultrastructural characteristics of rat SMG tissue and SMG-ECM-treated aggregates were remarkably similar.…”
Section: Autologous Multipotent Mscs As a Potential New Therapeutic P...mentioning
confidence: 77%
“… 163 More recently, we prepared ECM from decellularized rat SMG tissue, and investigated whether this matrix can direct the trans-differentiation of autologous BM-MSCs to the SG epithelial cell lineage in vitro. 221 We found that culture of BM-MSCs with homogenates of SMG-ECM for 14 days induced the formation of aggregates that expressed SG-specific epithelial cell lineage markers (AQP5, MUC10, KRT14, MIST1) and acinar-associated tight junction proteins (CLDN3 and CLDN10). In addition, the accumulation of glycoprotein/mucin, shown by PAS staining, correlated with the appearance on transmission electron micrographs (TEM) of tight junctions, secretory granule-like structures, and peripheral nuclei, suggesting that the cells were capable of functions associated with differentiated SG cells.…”
Section: Autologous Multipotent Mscs As a Potential New Therapeutic P...mentioning
confidence: 84%
“…Scale bar is shown in each panel. Images were selected from original work published by BioMed Central in Tran et al 221 …”
Section: Autologous Multipotent Mscs As a Potential New Therapeutic P...mentioning
confidence: 99%
“…Scale bar for SMG tissue = 50 µm; scale bar for aggregates implanted for 30 days = 20 µm. Images were selected from original work published by BioMed Central in Tran et al 221 …”
Section: Autologous Multipotent Mscs As a Potential New Therapeutic P...mentioning
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 suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the “immuno-privileged” status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient’s immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.
“…In addition, cellular transdifferentiation has been a controversial mechanism by which MSCs improve oral dryness. Previous studies have shown that MSCs can undergo a mesenchymal-to-epithelial transformation when induced by natural SG-specific extracellular matrix and then differentiate into corresponding salivary gland cells to repair damaged glands by replacing damaged salivary gland cells [ 55 ]. Furthermore, when MSCs are co-cultured with SGEC, MSCs can transdifferentiate into SGEC and promote amylase and mucopolysaccharide secretion from salivary gland epithelial cells by inducing salivary gland gene expression [ 45 ], promoting salivary secretion and alleviating oral dryness.…”
Background
Radiation-induced xerostomia and oral mucositis are serious complications of radiation therapy for head and neck cancers. Current treatment options have limited efficacy. Mesenchymal stem cell (MSC) therapy has shown promising results in supporting the restoration of glandular secretion function and the regeneration of damaged tissues. This study aim to (1) assess the quality of evidence for MSCs treatment in rodent models of radiation-induced oral complications and (2) determine whether MSCs can improve the therapeutic effect of radiation-induced oral mucositis.
Methods
Intervention studies using MSCs in rodent models were comprehensively retrieved in the Pubmed, Medline, Embase, Web of Science, and Cochrane library databases on June 1, 2022. The quality of all in vivo experiments was assessed using SYRCLE, and this article is written following the PRISMA guidelines.
Results
A total of 12 studies were included in this systematic review. The study found that in animal models of radiation-induced xerostomia, MSCs could increase salivary protein secretion, improve SFR, shorten the salivary lag time, anti-apoptosis, etc. In animal models of radiation-induced oral mucositis, MSCs improve the micromorphology and macromorphology of RIOM. Moreover, the effect of MSCs on the modification of ulcer duration and latency may be related to the time of MSCs transplantation but further studies are needed.
Conclusion
The results of our systematic review suggest that MSCs appeared to be effective in the treatment of radiation-induced xerostomia and oral mucositis.
Graphical Abstract
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