Resident CD34-positive cells contribute to peri-endothelial cells and vascular morphogenesis in salivary gland after irr
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NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE
Resident CD34‑positive cells contribute to peri‑endothelial cells and vascular morphogenesis in salivary gland after irradiation Takashi I1,2 · Yuichiro Ueda1 · Philipp Wörsdörfer1 · Yoshinori Sumita3 · Izumi Asahina2 · Süleyman Ergün1 Received: 16 March 2020 / Accepted: 22 September 2020 © The Author(s) 2020
Abstract Salivary gland (SG) hypofunction is a common post-radiotherapy complication. Besides the parenchymal damage after irradiation (IR), there are also effects on mesenchymal stem cells (MSCs) which were shown to contribute to regeneration and repair of damaged tissues by differentiating into stromal cell types or releasing vesicles and soluble factors supporting the healing processes. However, there are no adequate reports about their roles during SG damage and regeneration so far. Using an irradiated SG mouse model, we performed certain immunostainings on tissue sections of submandibular glands at different time points after IR. Immunostaining for CD31 revealed that already one day after IR, vascular impairment was induced at the level of capillaries. In addition, the expression of CD44—a marker of acinar cells—diminished gradually after IR and, by 20 weeks, almost disappeared. In contrast, the number of CD34-positive cells significantly increased 4 weeks after IR and some of the CD34-positive cells were found to reside within the adventitia of arteries and veins. Laser confocal microscopic analyses revealed an accumulation of CD34-positive cells within the area of damaged capillaries where they were in close contact to the CD31-positive endothelial cells. At 4 weeks after IR, a fraction of the CD34-positive cells underwent differentiation into α-SMA-positive cells, which suggests that they may contribute to regeneration of smooth muscle cells and/or pericytes covering the small vessels from the outside. In conclusion, SG-resident CD34-positive cells represent a population of progenitors that could contribute to new vessel formation and/or remodeling of the pre-existing vessels after IR and thus, might be an important player during SG tissue healing. Keywords Salivary gland · Xerostomia · Radiation · Resident CD34-positive cells · Mesenchymal stem cells Abbreviations CD Cluster of differentiation/cluster designation CXCR1 CXC chemokine receptor 1 IR Irradiation SFR Salivary flow rate SG Salivary gland Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00702-020-02256-1) contains supplementary material, which is available to authorized users. * Takashi I i‑takashi@nagasaki‑u.ac.jp 1
Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany
2
Unit of Translational Medicine, Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
3
Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
MSC Mesenchymal s
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