Analysis of lacrimal gland derived mesenchymal stem cell secretome and its impact on epithelial cell survival

Dietrich, Jana; Roth, Mathias; König, Simone; Geerling, Gerd; Mertsch, Sonja; Schrader, Stefan

doi:10.1016/j.scr.2019.101477

Cited by 18 publications

(29 citation statements)

References 59 publications

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“…The eGFP-MSC expressed nestin, which was previously shown to be expressed by MSC isolated from wild-type (wt) B6 LG (Fig. 2A,B) 26 . In addition, nestin and eGFP expression was stable (>99% each) over 28 days (Fig.…”

Section: Resultsmentioning

confidence: 65%

“…In a previous study, we identified lipocalin-2 (Lcn2) and STAT1 in the secretome of MSC, contributing to the improvement of LG epithelial cell survival in vitro 26 . Therefore, we analyzed whether transplanted MSC also secrete Lcn2 and/or STAT1 in vivo .…”

Section: Resultsmentioning

confidence: 99%

“…In the current study, MSC for transplantation were isolated by explant culture from mice that express eGFP in a constitutive and ubiquitous manner (eGFP-MSC). Recently, explant culture was identified as a suitable method to isolate a pure, specific and functional MSC population from the murine LG 8,26 . The eGFP expression allowed the identification and tracking of transplanted MSC throughout the study.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, genetic modification and ectopic expression of a transgene (eGFP) might alter the physiology of the cells. Therefore, eGFP-MSC were characterized and compared to results obtained from wildtype (wt) mice in previous studies 8,26 . eGFP-MSC exhibited the characteristic fibroblastic morphology and growth behaviors comparable to that of wt-MSC 22,26,30 .…”

Section: Discussionmentioning

confidence: 99%

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MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice

Dietrich

Ott

Roth

et al. 2019

Sci Rep

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Dry eye disease (DED) is a multifactorial disease characterized by a disrupted tear film homeostasis and inflammation leading to visual impairments and pain in patients. Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. Thus, the application of MSC appears to be a promising therapeutic approach to induce LG regeneration in patients suffering from severe DED/ADDE.

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Section: Resultsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice

Dietrich

Ott

Roth

et al. 2019

Sci Rep

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“…The concentration of FGF2 was relatively low in the whole conditioned medium, but it would be higher in the immediate vicinity of 3T3 fibers in the co-culture. Recently, cellular secretome such as one from mesenchymal stem cells [13][14][15] and myokine [16][17][18] have been attracting attention in terms of their potential therapeutic effects, though some of them yet to be identified. It is difficult to determine the chemical composition of the secretome.…”

Section: Discussionmentioning

confidence: 99%

Cell fibers promote proliferation of co-cultured cells on a dish

Shima

Itou

Takeuchi

2020

Sci Rep

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This paper describes a co-culture method using cell fiber technology. Cell fibers are cell-laden hydrogel microfibers, in which cells are cultured three-dimensionally and allowed to reach more mature state than the conventional two-dimensional cell culture. Cells in the cell fibers are encapsulated by alginate shell. Only cellular secretome is released into the surrounding environment through the shell while the cells were retained by the fiber. With their high handleability and retrievability, we propose to use the cell fibers for co-culture to ensure steady supply of cellular secretome. We cultured mouse C2C12 myoblasts with mouse 3T3 fibroblasts encapsulated in the cell fibers for two days. The number of C2C12 cells increased proportionally to the number of co-cultured 3T3 fibers, suggesting that the secretome of 3T3 fibers promoted survival and proliferation of C2C12 cells. We believe that cell fiber technology is a useful tool for co-culturing cells, and it will contribute to both basic cell biology and tissue engineering with its unique features.Co-culture, in which two or more types of cells are cultured together, is a major method to study interactions between different types of cells in vitro. Cells interact with each other both directly (via physical contact) and indirectly (via secreted molecules; for example, cytokines, growth factors and hormones) and these interactions have an impact on cellular survival, proliferation, differentiation and maturation. To investigate the indirect cellular interactions, two major methods have been established; one using culture inserts and the other using conditioned medium. Culture inserts make upper and lower compartments in culture wells, which enables a concurrent co-culture. Two different types of cells are plated and cultured in the upper and lower compartments. Only cellular secretome, but not the cells themselves, is then transferred between those two compartments through the pores on the bottom of culture inserts, when the pore size is smaller than the cells. On the other hand, in the method that employs conditioned medium, a certain type of cells are cultured and the supernatant containing their secretome (conditioned medium) is collected to subsequently culture the other type of cells. These methods are often employed and have been shown to be effective to study various cellular interactions 1-3 . However, neither of them is highly space-efficient; the number of available cells that provides secretome is limited because of the culture area.Cell fiber is a unique tool for culturing cells three-dimensionally for a long period until they differentiate into a mature tissue 4 . Cell fibers, which are cell-laden hydrogel microfibers formed by using a double-coaxial laminar-flow microfluidic device, consist of two parts; the core containing cells and extra cellular matrix (ECM) proteins such as collagen, and the alginate shell. Various types of cells have been shown to form three-dimensional (3D) tissues in cell fibers; for example, cardiomyocytes, vascular endoth...

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Lacrimal gland regeneration: The unmet challenges and promise for dry eye therapy

et al. 2022

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Analysis of lacrimal gland derived mesenchymal stem cell secretome and its impact on epithelial cell survival

Cited by 18 publications

References 59 publications

MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice

MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice

Cell fibers promote proliferation of co-cultured cells on a dish

Lacrimal gland regeneration: The unmet challenges and promise for dry eye therapy

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