Compressed Collagen Enhances Stem Cell Therapy for Corneal Scarring

Shojaati, Golnar; Khandaker, Irona; Sylakowski, Kyle; Funderburgh, Martha L.; Du, Yiqin; Funderburgh, James L.

doi:10.1002/sctm.17-0258

Cited by 39 publications

(33 citation statements)

References 27 publications

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“…Corneal cell type, isolation from donor corneas Scaffold not detected in rabbits 35 , no evidence in rabbits 43 , scar suppression in mice 76 No evidence available 57,58…”

Section: Human Donor Corneal Cellsmentioning

confidence: 99%

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Lagali

2019

Current Eye Research

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The corneal stroma comprises 90% of the corneal thickness and is critical for the cornea's transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of transparency can occur. Corneal stromal pathology is the cause of millions of cases of blindness globally, and although corneal transplantation is the standard therapy, a severe global deficit of donor corneal tissue and eye banking infrastructure exists, and is unable to meet the overwhelming need. An alternative approach is to harness the endogenous regenerative ability of the corneal stroma, which exhibits self-renewal of the collagenous extracellular matrix under appropriate conditions. To mimic endogenous stromal regeneration, however, is a challenge. Unlike the corneal epithelium and endothelium, the corneal stroma is an exquisitely organized extracellular matrix containing stromal cells, proteoglycans and corneal nerves that is difficult to recapitulate in vitro. Nevertheless, much progress has recently been made in developing stromal equivalents, and in this review the most recent approaches to stromal regeneration therapy are described and discussed. Novel approaches for stromal regeneration include human or animal corneal and/or non-corneal tissue that is acellular or is decellularized and/or recellularized, acellular bioengineered stromal scaffolds, tissue adhesives, 3D bioprinting and stromal stem cell therapy. This review highlights the techniques and advances that have achieved first clinical use or are close to translation for eventual therapeutic application in repairing and regenerating the corneal stroma, while the potential of these novel therapies for achieving effective stromal regeneration is discussed. ARTICLE HISTORY

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“…Corneal cell type, isolation from donor corneas Scaffold not detected in rabbits 35 , no evidence in rabbits 43 , scar suppression in mice 76 No evidence available 57,58…”

Section: Human Donor Corneal Cellsmentioning

confidence: 99%

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Lagali

2019

Current Eye Research

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“…Our previous work has shown that human corneal stroma contains a population of cells (human corneal stem cells, CSSC), which exhibit properties of MSCs and differentiate to corneal keratocytes [2][3][4][5][6][7][8][9]. These cells also block deposition of opaque scar tissue in a corneal wound healing model and elicit regeneration of normal, transparent stromal extracellular matrix [7,8,[10][11][12]. An important aspect of tissue regeneration effected by MSCs depends on their modification of tissue immune response by secretion of soluble factors to their environment [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Reduce Corneal Fibrosis and Inflammation via Extracellular Vesicle-Mediated Delivery of miRNA

Shojaati

Khandaker

Funderburgh

et al. 2019

Stem Cells Translational Medicine

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125

114

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Mesenchymal stem cells from corneal stromal stem cells (CSSC) prevent fibrotic scarring and stimulate regeneration of transparent stromal tissue after corneal wounding in mice. These effects rely on the ability of CSSC to block neutrophil infiltration into the damaged cornea. The current study investigated the hypothesis that tissue regeneration by CSSC is mediated by secreted extracellular vesicles (EVs). CSSC produced EVs 130–150 nm in diameter with surface proteins that include CD63, CD81, and CD9. EVs from CSSC reduced visual scarring in murine corneal wounds as effectively as did live cells, but EVs from human embryonic kidney (HEK)293T cells had no regenerative properties. CSSC EV treatment of wounds decreased expression of fibrotic genes Col3a1 and Acta2, blocked neutrophil infiltration, and restored normal tissue morphology. CSSC EVs labeled with carboxyfluorescein succinimidyl ester dye, rapidly fused with corneal epithelial and stromal cells in culture, transferring microRNA (miRNA) to the target cells. Knockdown of mRNA for Alix, a component of the endosomal sorting complex required for transport, using siRNA, resulted in an 85% reduction of miRNA in the secreted EVs. The EVs with reduced miRNA were ineffective at blocking corneal scarring. Furthermore, CSSC with reduced Alix expression also lost their regenerative function, suggesting EVs as an obligate component in the delivery of miRNA. The results of these studies support an essential role for extracellular vesicles in the process by which CSSC cells block scarring and initiate regeneration of transparent corneal tissue after wounding. EVs appear to serve as a delivery vehicle for miRNA, which affects the regenerative action. Stem Cells Translational Medicine 2019;8:1192–1201

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“…Compressed collagen hydrogels which contained hCSSCs was reported to suppress scar formation and improve regeneration of the injured tissue in mouse models with corneal scars in the anterior stroma. Lower inflammatory immune response was detected when fibrin gel was applied instead of sutures to implant the hydrogel to the damaged stroma [133].…”

Section: 222mentioning

confidence: 99%

Bioengineering Approaches for Corneal Regenerative Medicine

Mahdavi

Abdekhodaie

Mashayekhan

et al. 2020

Tissue Eng Regen Med

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BACKGROUND: Since the cornea is responsible for transmitting and focusing light into the eye, injury or pathology affecting any layer of the cornea can cause a detrimental effect on visual acuity. Aging is also a reason for corneal degeneration. Depending on the level of the injury, conservative therapies and donor tissue transplantation are the most common treatments for corneal diseases. Not only is there a lack of donor tissue and risk of infection/rejection, but the inherent ability of corneal cells and layers to regenerate has led to research in regenerative approaches and treatments. METHODS: In this review, we first discussed the anatomy of the cornea and the required properties for reconstructing layers of the cornea. Regenerative approaches are divided into two main categories; using direct cell/growth factor delivery or using scaffold-based cell delivery. It is expected delivered cells migrate and integrate into the host tissue and restore its structure and function to restore vision. Growth factor delivery also has shown promising results for corneal surface regeneration. Scaffold-based approaches are categorized based on the type of scaffold, since it has a significant impact on the efficiency of regeneration, into the hydrogel and non-hydrogel based scaffolds. Various types of cells, biomaterials, and techniques are well covered. RESULTS: The most important characteristics to be considered for biomaterials in corneal regeneration are suitable mechanical properties, biocompatibility, biodegradability, and transparency. Moreover, a curved shape structure and spatial arrangement of the fibrils have been shown to mimic the corneal extracellular matrix for cells and enhance cell differentiation. CONCLUSION: Tissue engineering and regenerative medicine approaches showed to have promising outcomes for corneal regeneration. However, besides proper mechanical and optical properties, other factors such as appropriate sterilization method, storage, shelf life and etc. should be taken into account in order to develop an engineered cornea for clinical trials.

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Compressed Collagen Enhances Stem Cell Therapy for Corneal Scarring

Cited by 39 publications

References 27 publications

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Mesenchymal Stem Cells Reduce Corneal Fibrosis and Inflammation via Extracellular Vesicle-Mediated Delivery of miRNA

Bioengineering Approaches for Corneal Regenerative Medicine

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