Orbital Fibroblasts From Graves' Orbitopathy Patients Share Functional and Immunophenotypic Properties With Mesenchymal Stem/Stromal Cells

Brandau, Sven; Bruderek, Kirsten; Hestermann, Khaleda; Görtz, Gina-Eva; Horstmann, Mareike; Mattheis, Stefan; Lang, Stephan; Eckstein, Anja; Berchner‐Pfannschmidt, Utta

doi:10.1167/iovs.15-16610

Cited by 21 publications

(15 citation statements)

References 32 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…OFs from GO patients have also been characterized [28–30]. Several studies have provided experimental evidence that OFs derived from retrobulbar fat of GO patients have similar immunophenotypic features and differentiation abilities as MSCs but differ in terms of their immunosuppressive potential [28, 29]. Furthermore, comparative analyses of adipose-derived MSCs from GO orbital fat and abdominal fat have been conducted to understand the phenotypic characteristics of OFs in GO patients [30].…”

Section: Discussionmentioning

confidence: 99%

Human placenta-derived mesenchymal stem cells ameliorate orbital adipogenesis in female mice models of Graves’ ophthalmopathy

et al. 2019

View full text Add to dashboard Cite

Background: Graves' ophthalmopathy (GO) is a complication of Graves' disease (GD), in which orbital connective tissues become inflamed and increase in volume and orbital fibroblasts within the orbital fat and extraocular muscles differentiate into adipocytes in vitro when stimulated by hormones, several cytokines, and growth factors including TSH, IGF-1, IL-1, interferon γ, and platelet-derived growth factor. Human placental mesenchymal stem cells (hPMSCs) have immunomodulatory effects in disease pathogenesis. Although a number of studies have reported that hPMSCs can elicit therapeutic effects, these are not sufficient. Therefore, we constructed a GO animal model in order to find out the hPMSCs recovery effect. Methods: We investigated their anti-adipogenic effects in in vitro cultures of orbital fibroblasts established from GO patients. Primary orbital fibroblasts were exposed to differentiation medium for 10 days. After being co-cultured with hPMSCs, the characteristics of orbital fibroblast were determined by Oil Red O stain and real-time PCR. Then, we explored the in vivo regulatory effects of hPMSCs in an experimental mouse model of GO. We developed the GO mouse model using immunization by leg muscle electroporation of pTriEx1.1Neo-hTSHR A-subunit plasmid. Human PMSC injection was performed into the left orbit. We also analyzed the effects of hPMSCs in the GO animal model. Result: We found that hPMSCs inhibited a lipid accumulation and activated factors, such as ADIPONECTIN, PPARγ, C/EBPα, and TGFβ2 genes in adipogenesis-induced primary orbital fibroblasts from GO patients. Moreover, hPMSCs were highly effective at ameliorating adipogenesis in the orbital tissue of the model. Conclusion: These data indicate that hPMSCs recover pathogenic activation of orbital fibroblasts in animals undergoing experimental GO and confirm the feasibility of applying hPMSCs as a novel treatment for GO patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Human placenta-derived mesenchymal stem cells ameliorate orbital adipogenesis in female mice models of Graves’ ophthalmopathy

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Analysis by flow cytometry has shown that orbital fibroblasts are largely positive for CD90 (Thy-1) and negative for CD45 85,86 (Figure 2). There is potential for strategies that use the suppressive function of regulatory T cells to also prove beneficial to patients with Graves' orbitopathy 91 .…”

Section: [H2] Rituximabmentioning

confidence: 99%

New insights into the pathogenesis and nonsurgical management of Graves orbitopathy

et al. 2019

View full text Add to dashboard Cite

Graves' orbitopathy, also known as thyroid eye disease or thyroid-associated orbitopathy, is visually disabling, cosmetically disfiguring and has a substantial negative impact on a patients' quality of life. There is increasing awareness of the need for early diagnosis and rapid specialist input from endocrinologists and ophthalmologists. Glucocorticoids are the mainstay of treatment; however, recurrence occurs frequently once these are withdrawn. Furthermore, in >60% of cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required to reduce disfigurement, double vision and occasionally, to preserve vision. Clinical trials from over the past decade [Au: edits to define "recent" OK? Please edit my changes if I have misunderstood you This is fine] have shown that considerable benefit can be derived from the addition of anti-proliferative agents (such as mycophenolate or azathioprine) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab (anti-IGF-1R), which seems to substantially reduce proptosis, rituximab (anti-CD20), which reduces inflammation, and tocilizumab, which potentially benefits both of these parameters. Other strategies such as orbital radiotherapy have had their widespread role in combination therapy called into question. In the last decade, the pathophysiology of Graves' orbitopathy has also been revised with identification of new potential therapeutic targets. In this review we provide an up-to-date overview of the field, [Au: addition of linking text OK? This is fine] outline the optimal management of Graves' orbitopathy and summarise the research developments in this area to highlight future research questions and direct future clinical trials.

show abstract

“…While these studies suggested potential site-specific differences between fibroblasts, direct comparison of fibroblasts derived from different adipose tissue depots of the same donors has not been reported. On the other hand, Brandau et al 15 demonstrated comparable immunophenotypic and multipotent properties yet distinct functional differences between orbital fibroblasts derived from explant culture and ADSC generated by enzymatic digestion using the same aliquot of orbital adipose tissues from patients with TAO. Whether ADSC from patients with TAO demonstrates such site-specific features is not known.…”

Section: Discussionmentioning

confidence: 99%

Depot-specific characteristics of adipose tissue-derived stromal cells in thyroid-associated orbitopathy

Wong

Chu

et al. 2018

Br J Ophthalmol

View full text Add to dashboard Cite

show abstract

Orbital Fibroblasts From Graves' Orbitopathy Patients Share Functional and Immunophenotypic Properties With Mesenchymal Stem/Stromal Cells

Abstract: The in vitro data obtained in this study provide the first experimental evidence that orbital fibroblasts derived from retrobulbar fat of GO patients share biological characteristics with MSCs. These findings provide new insight into the biology of key cells in GO.

Cited by 21 publications

References 32 publications

Human placenta-derived mesenchymal stem cells ameliorate orbital adipogenesis in female mice models of Graves’ ophthalmopathy

Human placenta-derived mesenchymal stem cells ameliorate orbital adipogenesis in female mice models of Graves’ ophthalmopathy

New insights into the pathogenesis and nonsurgical management of Graves orbitopathy

Depot-specific characteristics of adipose tissue-derived stromal cells in thyroid-associated orbitopathy

Contact Info

Product

Resources

About