The Role of Exogenous/Endogenous Basic Fibroblast Growth Factor (FGF2) and Transforming Growth Factor β (TGFβ-1) on Human Corneal Endothelial Cells Proliferation in Vitro

Rieck, Peter; Oliver, Lisa; Engelmann, Katrin; Fuhrmann, Gregor; Hartmann, Christian; Courtois, Yves

doi:10.1006/excr.1995.1289

Cited by 32 publications

(24 citation statements)

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“…We subsequently learned that this pathological state is initiated by proliferation as a result of canonical Wnt signaling in the presence of EGF and/or bFGF and becomes irreversible with cessation of proliferation when TGF-β1 is added to trigger canonical TGF-β signaling with nuclear translocation of pSmad2/3 and Zeb1/2[29]. Our finding is consistent with several prior studies showing that TGF-β1/2 suppress proliferation promoted by bFGF in EDTA-treated HCEC[30], rat CEC[31], and bovine CEC[32], and that the use of SB431542, a selective inhibitor of the TGF-βR, prevents EMT in monkey and HCEC[33]. Because the outcome is EMT with the loss of the normal HCEC phenotype, one strategy of engineering HCEC should be directed to avoiding activation of canonical Wnt-Smad2/3-Zeb1/2 signaling.…”

Section: Isolation Of Human Corneal Endothelial Cellssupporting

confidence: 89%

Engineering of Human Corneal Endothelial Grafts

Zhu

Tighe

Chen

et al. 2015

Curr Ophthalmol Rep

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Human corneal endothelial cells (HCEC) play a pivotal role in maintaining corneal transparency. Unlike in other species, HCEC are notorious for their limited proliferative capacity in vivo after diseases, injury, aging, and surgery. Persistent HCEC dysfunction leads to sight-threatening bullous keratopathy with either an insufficient cell density or retrocorneal membrane due to endothelial-mesenchymal transition (EMT). Presently, the only solution to restore vision in eyes inflicted with bullous keratopathy or retrocorneal membrane relies upon transplantation of a cadaver human donor cornea containing a healthy corneal endothelium. Due to a severe global shortage of donor corneas, in conjunction with an increasing trend toward endothelial keratoplasty, it is opportune to develop a tissue engineering strategy to produce HCEC grafts. Prior attempts of producing these grafts by unlocking the contact inhibition-mediated mitotic block using trypsin-EDTA and culturing of single HCEC in a bFGF-containing medium run the risk of losing the normal phenotype to EMT by activating canonical Wnt signaling and TGF-β signaling. Herein, we summarize our novel approach in engineering HCEC grafts based on selective activation of p120-Kaiso signaling that is coordinated with activation of Rho-ROCK-canonical BMP signaling to reprogram HCEC into neural crest progenitors. Successful commercialization of this engineering technology will not only fulfill the global unmet need but also encourage the scientific community to re-think how cell-cell junctions can be safely perturbed to uncover novel therapeutic potentials in other model systems.

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Section: Isolation Of Human Corneal Endothelial Cellssupporting

confidence: 89%

Engineering of Human Corneal Endothelial Grafts

Zhu

Tighe

Chen

et al. 2015

Curr Ophthalmol Rep

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“…[3][4][5][6][7] As a culture medium supplement, FGF-2 was shown to sustain corneal endothelial cell survival and proliferation in serum-reduced and serum-free culture media. 1,2,4,5,[8][9][10][11][12][13] Furthermore, after cell transplantation of corneal endothelial cells on denuded donor corneas, addition of FGF-2 to the organ culture medium supported a differentiated morphology of the transplanted cells, although it did not promote cell proliferation in situ. 14,15 To date, five isoforms of FGF-2 are known.…”

Section: Purposementioning

confidence: 99%

Overexpression of Human HMW FGF-2 but Not LMW FGF-2 Reduces the Cytotoxic Effect of Lentiviral Gene Transfer in Human Corneal Endothelial Cells

Valtink¹,

Knels²,

Stanke

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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“…Bovine and human corneal endothelial cells contain poly-a positive RNA coding for FGF-2 and the growth factor is produced by these cells (Schweigerer et al, 1988;Wilson and Lloyd, 1991;Rieck et al, 1995). In addition, extracellular FGF-2 is present in the basement membrane underlying the endothelium, suggesting that FGF-2 may act in an autocrine or paracrine manner to stimulate migration of these cells (Vlodavsky et al, 1987).…”

Section: Introductionmentioning

confidence: 96%