Abstract
Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries.
Highlights
Acinar and ductal cells in the salivary glands are fundamental units of saliva production and s secretion
We observed that fibroblast-like mesenchymal stem cells (mMSCs) have altered their shape into round epithelial-like
Since morphological and molecular changes in the transdifferentiated mMSCs were mainly observed within 24 h of co-culture [25,26], we primarily focused on our analysis for day 1
Summary
Acinar and ductal cells in the salivary glands are fundamental units of saliva production and s secretion. Current treatment options are limited to palliative approaches, such as saliva substitutes and systemic secretagogues (pilocarpine or cevimeline) that stimulate saliva secretion from the residual acinar cells [7,8]. Salivary regenerative methods are focused on cell-based approaches, which necessitate the identification of potential progenitors or resident stem cells in order to substitute damaged ductal and acinar cells. Several studies have reported the presence of stem cell populations in mouse, rat, and human salivary glands. The scarcity of these cells has raised a challenge [10,11]. Utilization of a more abundant source of stem cells, such as bone marrow- and adipose-derived stem cells, has been explored to overcome this challenge
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