Stromal fibroblasts are associated with collagen IV in scar tissues of alkali-burned and lacerated corneas

Ishizaki, Masamichi; Shimoda, Mariko; Wakamatsu, Kyoko; Ogro, Tatsuo; Yamanaka, Nobuaki; Kao, Candace W.-C.; Kao, Winston W.‐Y.

doi:10.1076/ceyr.16.4.339.10684

Cited by 34 publications

(21 citation statements)

References 12 publications

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“…They fail to repair damaged corneal stroma, although they proliferate and assume myofibroblast phenotypes of scar tissue. 13–15 In addition, there is a lack of definitive marker(s) that can aid the identification of MSC. 6 However, cell surface markers that are characteristic of MSC have been reported and are associated with the identity of MSC; for example CD44, CD105, CD73, and CD90, but not CD45, CD19, CD79, CD14, CD11b or HLA-DR.…”

Section: Introductionmentioning

confidence: 99%

Cell Therapy of Corneal Diseases

Kao

Coulson‐Thomas²

2016

Cornea

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Mesenchymal stem cells (MSC) isolated from connective tissues are pluripotent and differentiate to phenotypes of connective tissue cell lineages (osteoblasts, chondrocytes, adipocytes) in vitro and in vivo. They have been used to treat mouse models of connective tissue disease such as Lumican null (Lum−/−), and mucopolysaccharidosis (Gusb) mice. MSC have unique immunosuppressive properties allowing evasion of host rejection; thus, they are valuable tools for cell therapy of congenital and acquired diseases involving immune dysfunction of multiple tissues including ocular surface tissues (cornea). We previously showed that human umbilical mesenchymal stem cells (UMSCs) modulated host immune responses, enabling them to survive xenograft transplantations. In vitro UMSCs modulated inflammatory cells by inhibiting adhesion and invasion, and inducing cell death. UMSC also regulated M1/M2 macrophage polarization and induced T-regulatory cell maturation from naïve intraperitoneal cavity lavage cells. UMSCs exposed to inflammatory cells synthesized a rich extracellular glycocalyx composed of hyaluronan (HA) bound to the heavy chains (HCs) of inter-alpha-trypsin inhibitor (HC-HA), which contains tumor necrosis factorα-stimulated gene 6 (TSG6) that catalyzes the transfer of HCs to HA, versican and pentraxin-3. Our in vivo and in vitro results showed that glycocalyx regulated inflammatory cells, allowing UMSCs to survive host immune rejection. Administration of antibodies against glycocalyx constituents or digestion with hyaluronidase and chondroitinase ABC abolished the UMSC ability to modulate immune responses. Treatment with anti-CD44 antibodies also diminished modulation of M2 macrophages by UMSC, indicating cell surface CD44 is required for correct UMSC glycocalyx assembly to modulate inflammatory cells.

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Section: Introductionmentioning

confidence: 99%

Cell Therapy of Corneal Diseases

Kao

Coulson‐Thomas²

2016

Cornea

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“…Previous studies demonstrated deposition of collagen IV in rabbit corneal stroma injured by alkali burns or lacerations, and its association with fibroblast activation and scar tissue [20,21]. Similarly, α-SMA expression is the hallmark for myofibroblast differentiation, the cells responsible for stromal haze and scarring [12,22].…”

Section: Discussionmentioning

confidence: 97%

Long-term follow-up of a supradescemetic keratoprosthesis in rabbits: an immunofluorescence study

Espana

Acosta

Stoiber

et al. 2010

Graefes Arch Clin Exp Ophthalmol

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“…Deposition of Coll-IV was also found in rabbit corneal stroma injured by alkali burns or laceration, was associated with activated stromal fibroblasts, and was thought to be the reason for forming opaque granulation tissue. 7 In the early stage of wound healing, fibronectin exudated from the plasma or tears and secreted by activated fibroblasts is deposited in the corneal stroma as a provisional matrix. Fn is completely reabsorbed when the wound healing process is completed.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, we analysed the expression of collagen IV (Coll-IV), a basement membrane component, which is expressed by injured corneal stromal fibroblasts. 7 We also studied fibronectin (Fn), a provisional matrix component, which is expressed by stromal fibroblasts during early and active wound healing. 8 Furthermore, we determined whether fibroblasts expressed a-smooth muscle actin (a-SMA), a marker of myofibroblasts, 9 responsible for corneal wound contraction.…”

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confidence: 99%

Corneal stromal changes following reconstruction by ex vivo expanded limbal epithelial cells in rabbits with total limbal stem cell deficiency

Espana

Ti²,

Grueterich³

et al. 2003

British Journal of Ophthalmology

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Aim: To study corneal stromal changes and the presence of myofibroblasts after transplantation of ex vivo expanded limbal epithelium. Methods: A state of limbal deficiency was induced in 16 rabbits. After transplantation with autologous ex vivo expanded limbal epithelium on amniotic membrane (AM), their clinical outcomes were classified as success, partial success or failure according to surface smoothness, stromal clarity, and vascularisation. Clinical outcomes were correlated with phenotypic outcomes of corneal, conjunctival, or mixed epithelium, defined by expression of K3 keratin or MUC5AC. Immunostaining was performed with antibodies against collagen IV, fibronectin, and a-smooth muscle actin (a-SMA) to assess stromal wound remodelling. Results: Rabbits were sacrificed after a mean follow up of 10 (SD 3.3) months. Collagen IV, expressed in the basement membrane of all three groups, was found in the stroma of the partial success, but not in that of the success or the failure. Fibronectin was absent in the success and the failure, but expressed in the stroma of the partial success. a-SMA was expressed in superficial stroma of the partial success, but suppressed in areas with AM remnants. Conclusion: Restoration of a clear and transparent cornea is associated with a normal corneal epithelium and complete wound remodelling. In contrast, wound healing remains active and incomplete in conjunctivalised corneas, which remain opaque with myofibroblasts.

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Stromal fibroblasts are associated with collagen IV in scar tissues of alkali-burned and lacerated corneas

Abstract: The enhanced expression of collagen IV by the fibroblastic cells in the stroma of injured corneas is consistent with the notion that they may contribute to the formation of basal lamina-like structures in injured corneas.

Cited by 34 publications

References 12 publications

Cell Therapy of Corneal Diseases

Cell Therapy of Corneal Diseases

Long-term follow-up of a supradescemetic keratoprosthesis in rabbits: an immunofluorescence study

Corneal stromal changes following reconstruction by ex vivo expanded limbal epithelial cells in rabbits with total limbal stem cell deficiency

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