Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor

Mittal, Sanjay; Foulsham, William; Shukla, Sachin; Elbasiony, Elsayed; Omoto, Masahiro; Chauhan, Sunil

doi:10.1002/sctm.19-0004

Cited by 32 publications

(23 citation statements)

References 46 publications

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“…91 Most recently, Mittal et al have reported that MSCs modulate corneal alloimmunity and promote graft survival via secretion of HGF. 92 Previous studies have also shown that other growth factors like transforming growth factor-β (TGFβ) and platelet-derived growth factor (PDGF) also play important roles in corneal stromal wound healing. Bone marrow cells can also move to wounded site for repair along with limbal stromal cells and may help to prevent fibrosis.…”

Section: Cssc/lmscs and Corneal Stromal Wound Healingmentioning

confidence: 99%

Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration

Shukla

Shanbhag

Tavakkoli

et al. 2019

Current Eye Research

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Corneal pathologies are a major cause of blindness and visual impairment, especially in the developing world. However, not only is there a global shortage of donor corneal tissue, but a significant proportion of these blinding pathologies also carry an unfavourable long-term prognosis for conventional corneal transplantation. In the last few decades, there has been a spurt of research on developing alternate approaches to address corneal blindness, including stem cell therapy. After the discovery of epithelial stem cells at the limbus, successful cell-based approaches to treat severe ocular surface disease were developed and have subsequently become widely practised across the world. More recently, mesenchymal stem cells were identified near the epithelial stem cells at the limbus, providing a unique opportunity to develop regenerative therapies for both corneal epithelial and stromal pathologies. This review firstly emphasises on qualifying limbal stem cells as either epithelial or mesenchymal and then summarises all the existing knowledge on both cell types and their individual roles in corneal regeneration. The review describes the history, indications, techniques, and outcomes of the different methods of limbal epithelial stem cell transplantation and elaborates on the potential applications of limbal mesenchymal stem cell therapy. ARTICLE HISTORY

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Section: Cssc/lmscs and Corneal Stromal Wound Healingmentioning

confidence: 99%

Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration

Shukla

Shanbhag

Tavakkoli

et al. 2019

Current Eye Research

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“…The upregulated genes included pentraxin 3 (PTX3), tumor necrosis factor-inducible gene 6 (TSG-6), and cyclooxygenase-2 (COX-2), which are well-known to mediate the immunomodulatory actions of MSCs [ 7 , 8 , 9 , 10 , 11 , 12 ]. Meanwhile, hepatocyte growth factor (HGF) and stanniocalcin 1 (STC-1), other therapeutic factors expressed by MSCs [ 13 , 14 , 15 ], were among the downregulated genes in miR-146a inhibitor-MSCs. The expression of these immunoregulatory molecules was further validated by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA) ( Figure 2 C,D).…”

Section: Resultsmentioning

confidence: 99%

The Effect of miR-146a on the Gene Expression of Immunoregulatory Cytokines in Human Mesenchymal Stromal Cells

2020

IJMS

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Mounting evidence indicates that microRNAs (miRNAs), including miR-146a, have an impact on the immunomodulatory activities of mesenchymal stem/stromal cells (MSCs). Suppression of inflammatory macrophage activation is one of the main immunomodulatory mechanisms of MSCs. Here, we investigated whether miR-146a in MSCs might play a role in the effects of MSCs on macrophage activation. A miRNA microarray revealed that miR-146a was the most highly upregulated miRNA in MSCs upon co-culture with activated macrophages. Inhibition of miR-146a in MSCs through miR-146a inhibitor transfection had a different effect on the expression of immunoregulatory factors secreted by MSCs. Pentraxin 3, tumor necrosis factor-inducible gene 6, and cyclooxygenase-2, which are well-known mediators of the immunomodulatory functions of MSCs, were significantly upregulated in MSCs after miR-146a knockdown. By contrast, hepatocyte growth factor and stanniocalcin 1, other immunoregulatory molecules expressed by MSCs, were downregulated by miR-146a knockdown. Consequently, the inhibition of miR-146a in MSCs did not change the overall effect of MSCs on the suppression of inflammatory macrophage activation or the induction of anti-inflammatory macrophage polarization.

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“…HGF has also been implicated as a fundamental factor in immunomodulation, secreted by MSCs stimulated with IL-1ß. 38 HGF alone is powerful enough to suppress antigen presenting cell activation and to limit the generation of Th1 cells in the lymphoid tissue. Topical HGF application significantly reduced the rejection of corneal grafts in a murine model of GVHD, through suppression of immune cell infiltration, and has the potential to maintain and restore corneal transparency through the inhibition of α-SMA and its inducer TGF-ß.…”

Section: Paracrine Signalling Of Mscs and Potential Effect On Cornementioning

confidence: 99%

“…HGF has also been implicated as a fundamental factor in immunomodulation, secreted by MSCs stimulated with IL‐1ß 38 . HGF alone is powerful enough to suppress antigen presenting cell activation and to limit the generation of Th1 cells in the lymphoid tissue.…”

Section: Paracrine Signalling Of Mscs and Potential Effect On Cornealmentioning

confidence: 99%

Potential of mesenchymal stem cells as topical immunomodulatory cell therapies for ocular surface inflammatory disorders

Beeken

Ting

Sidney

2020

Stem Cells Translational Medicine

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Ocular surface inflammatory disorders (OSIDs) are a group of highly prevalent, heterogeneous diseases which display a variety of aetiologies and symptoms and are risk factors for serious complications including ocular and cornea impairment. Corneal inflammation is a common factor of all OSIDs, regardless of their cause or symptoms. Current medications include over-the-counter lubricating eye drops, corticosteroids, and ciclosporin, which either do not treat the corneal inflammation or have been associated with multiple side effects leading to alternative treatments being sought. Regenerative medicine cell therapies, particularly mesenchymal stem cells (MSCs), have shown great promise for immunosuppression and disease amelioration across multiple tissues, including the cornea. However, for successful development and clinical translation of MSC therapy for OSIDs, significant problems must be addressed. This review aims to highlight considerations, including whether the source of MSC isolation impacts the efficacy and safety of the therapy, in addition to assessing the feasibility of MSC topical application to the cornea and ocular surface through analysis of potential scaffolds and cell carriers for application to the eye. The literature contains limited data assessing MSCs incorporated into scaffolds for corneal administration, thus here we highlight the necessity of further investigations to truly exploit the potential of an MSC-based cell therapy for the treatment of OSIDs.

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Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor

Cited by 32 publications

References 46 publications

Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration

Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration

The Effect of miR-146a on the Gene Expression of Immunoregulatory Cytokines in Human Mesenchymal Stromal Cells

Potential of mesenchymal stem cells as topical immunomodulatory cell therapies for ocular surface inflammatory disorders

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