Immunoregulatory Properties of Mouse Limbal Stem Cells

Holáň, Vladimı́r; Pokorná, Kateřina; Procházková, Jana; Krulová, Magdaléna; Zajı́cová, Alena

doi:10.4049/jimmunol.0903049

Cited by 24 publications

(14 citation statements)

References 37 publications

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“…1B) and by their capability to inhibit anti-CD3 induced T-cell proliferation (Fig. 1C), consistent with our previous results [27,28]. In addition, we confirmed a specific adipogenic and osteogenic differentiation of MSCs by expression of adipocyte-and osteoblaste-specific markers by real-time PCR (data not shown).…”

Section: Characterization Of Mscssupporting

confidence: 92%

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The Role of Mouse Mesenchymal Stem Cells in Differentiation of Naive T-Cells into Anti-Inflammatory Regulatory T-Cell or Proinflammatory Helper T-Cell 17 Population

Svobodová

Krulová

Zajı́cová

et al. 2012

Stem Cells and Development

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101

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Bone marrow-derived mesenchymal stem cells (MSCs) modulate immune response and can produce significant levels of transforming growth factor-b (TGF-b) and interleukin-6 (IL-6). These 2 cytokines represent the key factors that reciprocally regulate the development and polarization of naive T-cells into regulatory T-cell (Treg) population or proinflammatory T helper 17 (Th17) cells. In the present study we demonstrate that MSCs and their products effectively regulate expression of transcription factors Foxp3 and RORgt and control the development of Tregs and Th17 cells in a population of alloantigen-activated mouse spleen cells or purified CD4 + CD25-T-cells. The immunomodulatory effects of MSCs were more pronounced when these cells were stimulated to secrete TGF-b alone or TGF-b together with IL-6. Unstimulated MSCs produce TGF-b, but not IL-6, and the production of TGF-b can be further enhanced by the anti-inflammatory cytokines IL-10 or TGF-b. In the presence of proinflammatory cytokines, MSCs secrete significant levels of IL-6, in addition to a spontaneous production of TGF-b. MSCs producing TGF-b induced preferentially expression of Foxp3 and activation of Tregs, whereas MSC supernatants containing TGF-b together with IL-6 supported RORgt expression and development of Th17 cells. The effects of MSC supernatants were blocked by the inclusion of neutralization monoclonal antibody anti-TGF-b or anti-IL-6 into the culture system. The results showed that MSCs represent important players that reciprocally regulate the development and differentiation of uncommitted naive T-cells into anti-inflammatory Foxp3 + Tregs or proinflammatory RORgt + Th17 cell population and thereby can modulate autoimmune, immunopathological, and transplantation reactions.

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Section: Characterization Of Mscssupporting

confidence: 92%

“…Quantitative real-time polymerase chain reaction (PCR) was performed on an iCycler (BioRad, Hercules, CA) as we have previously described [28,29]. The primers used for amplification were as follows:…”

Section: Detection Of Tgf-b and Il-6 Gene Expression By Real-time Polmentioning

confidence: 99%

The Role of Mouse Mesenchymal Stem Cells in Differentiation of Naive T-Cells into Anti-Inflammatory Regulatory T-Cell or Proinflammatory Helper T-Cell 17 Population

Svobodová

Krulová

Zajı́cová

et al. 2012

Stem Cells and Development

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101

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“…The expression of Fas and FasL in the target cell was reported to be one of the protective mechanisms against lymphocyte attack that promote target cell survival. [33][34][35][36][37][38] Our results showed that there was no significant complement-dependent TDSC lysis. This was consistent with two recent reports that MSCs inhibited complement activation due to the production of factor H and absence of HLA-B.…”

Section: Discussionmentioning

confidence: 55%

Allogeneic Tendon-Derived Stem Cells Promote Tendon Healing and Suppress Immunoreactions in Hosts:In VivoModel

Lui

Kong

Lau

et al. 2014

Tissue Engineering Part A

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The medium- to long-term healing effect and infiltration of inflammatory cells, after transplantation of allogeneic tendon-derived stem cell (TDSC) to the rat patellar tendon window wound, were examined. Allogeneic patellar TDSCs derived from a green fluorescent protein rat were used. The outcome of tendon healing and the infiltration of inflammatory cells were examined by histology and immunohistochemistry up to week 16 postinjury. The fate of the transplanted cells was examined by ex vivo fluorescent imaging and immunohistochemistry. Our results showed that the transplantation of allogeneic TDSCs promoted tendon healing with no increased risk of ectopic chondro-ossification up to week 16. A low infiltration of T cells, ED1 macrophages, ED2 macrophages, and mast cells in the window wound was obtained. The transplanted TDSCs were found in the window wound at week 1 and 2, but were absent after week 4 postinjury. In conclusion, allogeneic TDSCs promoted tendon repair in the medium to long term and exhibited weak immunoreactions and anti-inflammatory effects in the hosts after transplantation in a rat model. There was no increased risk of ectopic chondro-ossification after TDSC transplantation. The decrease in the number of transplanted cells with time suggested that allogeneic TDSCs did not promote tendon repair through direct differentiation.

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“…The first-strand cDNA was synthesized using random primers (Promega, Madison, WI) in a total reaction volume of 25 mL using M-MLV Reverse Transcriptase (Promega). Quantitative real-time PCR was performed in an iCycler (BioRad, Hercules, CA), as previously described [25,26]. The primers used for amplification are shown in Table 1.…”

Section: Detection Of Gene Expression By Real-time Polymerase Chain Rmentioning

confidence: 99%

The Key Role of Insulin-Like Growth Factor I in Limbal Stem Cell Differentiation and the Corneal Wound-Healing Process

Trošan

Svobodová

Chudíčková

et al. 2012

Stem Cells and Development

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Limbal stem cells (LSC), which reside in the basal layer of the limbus, are thought to be responsible for corneal epithelial healing after injury. When the cornea is damaged, LSC start to proliferate, differentiate, and migrate to the site of injury. To characterize the signaling molecules ensuring communication between the cornea and LSC, we established a mouse model of mechanical corneal damage. The central cornea or limbal tissue was excised at different time intervals after injury, and the expression of genes in the explants was determined. It was observed that a number of genes for growth and differentiation factors were significantly upregulated in the cornea rapidly after injury. The ability of these factors to regulate the differentiation and proliferation of limbal cells was tested. It was found that the insulin-like growth factor-I (IGF-I), which is rapidly overexpressed after injury, enhances the expression of IGF receptor in limbal cells and induces the differentiation of LSC into cells expressing the corneal cell marker, cytokeratin K12, without any effect on limbal cell proliferation. In contrast, the epidermal growth factor (EGF) and fibroblast growth factor-b (FGF-b), which are also produced by the damaged corneal epithelium, supported limbal cell proliferation without any effect on their differentiation. Other factors did not affect limbal cell differentiation or proliferation. Thus, IGF-I was identified as the main factor stimulating the expression of IGF receptors in limbal cells and inducing the differentiation of LSC into cells expressing corneal epithelial cell markers. The proliferation of these cells was supported by EGF and FGF.

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Immunoregulatory Properties of Mouse Limbal Stem Cells

Cited by 24 publications

References 37 publications

The Role of Mouse Mesenchymal Stem Cells in Differentiation of Naive T-Cells into Anti-Inflammatory Regulatory T-Cell or Proinflammatory Helper T-Cell 17 Population

The Role of Mouse Mesenchymal Stem Cells in Differentiation of Naive T-Cells into Anti-Inflammatory Regulatory T-Cell or Proinflammatory Helper T-Cell 17 Population

Allogeneic Tendon-Derived Stem Cells Promote Tendon Healing and Suppress Immunoreactions in Hosts:In VivoModel

The Key Role of Insulin-Like Growth Factor I in Limbal Stem Cell Differentiation and the Corneal Wound-Healing Process

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