Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors

International Journal of Molecular Sciences

卷:21

Mi-Jeong Yoo¹  Firas Kobeissy²  Yun-Jong Park³  Jin Koh⁴  Sixue Chen⁴  Wafaa Saleh⁵  Seunghee Cha⁶  Mahmoud Mona⁶  Rehae Miller⁶ 

[1] Department of Biology, Clarkson University, Potsdam, NY 13699, USA;

[2] Department of Emergency Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA;

[3] Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993 USA;

[4] Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL 32610, USA;

[5] Oral Medicine and Periodontology Department, Faculty of Dentistry, Mansoura University, Mansoura 35516, Egypt;

[6] Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL 32610, USA;

关键词: mouse bone marrow-derived stem cells (mMSC);    co-culture;    secretome;    salivary glands;    Sjögren’s Syndrome;    salivary progenitors;   

DOI  :  10.3390/ijms21239055

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown