The Graft of Autologous Adipose-Derived Stem Cells in the Corneal Stromal after Mechanic Damage

Ma, Xiaoli; Bao, Hui-jing; Cui, Lei; Zou, Jun

doi:10.1371/journal.pone.0076103

Cited by 35 publications

(25 citation statements)

References 34 publications

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“…When these cells were injected into wounded corneas, these cells prevented fibrotic scar formation and contributed to the regeneration of stromal ECM with lamellar structure and collagen organization typical for normal corneas (Basu et al, 2014). Overall, these studies open up new avenues for fibrosis treatment with a possibility for using autologous sources, such as limbal biopsies or adipose derived stem cells (Ma et al, 2013). …”

Section: Corneal Stromal Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

644

554

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Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.

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Section: Corneal Stromal Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

644

554

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“…The majority of studies have been performed using MSC derived from either bone marrow (13 studies) [13, 14, 17, 22–24, 38–40, 43, 47, 48, 50] or adipose tissue (9 studies) [19, 33, 35, 42, 44–46, 49, 51], with the remainder using MSC extracted from either umbilical cord tissues (4 studies) or dental pulp (2 studies) . Most studies have used cultures of MSC established from human tissues (19 studies) [13, 18–20, 23, 24, 33–39, 41, 42, 45, 46, 49, 51], with the balance having been established from rabbits (5 studies) , rats (3 studies) , and mice (1 study) .…”

Section: Overview Of Published Literaturementioning

confidence: 99%

“…The majority of studies have been performed using MSC derived from either bone marrow (13 studies) [13, 14, 17, 22-24, 38-40, 43, 47, 48, 50] or adipose tissue (9 studies) [19, 33, 35, 42, 44-46, 49, 51], with the remainder using MSC extracted from either umbilical cord tissues (4 studies) [20,34,36,41] or dental pulp (2 studies) [18,37]. Most studies have used cultures of MSC established from human tissues (19 studies) [13, 18-20, 23, 24, 33-39, 41, 42, 45, 46, 49, 51], with the balance having been established from rabbits (5 studies) [14,17,43,44,48], rats (3 studies) [40,47,50], and mice (1 study) [22]. A large proportion of studies (19 studies) [13, 14, 17, 18, 20, 22, 24, 33-35, 37, 38, 40, 42-44, 47-49] have involved in vivo experiments, with 11 studies involving administration of human MSC into rabbits (6 studies) [18,33,35,37,38,42], rats (3 studies) [13,24,49], or mice (2 studies) [20,34].…”

Section: Overview Of Published Literaturementioning

confidence: 99%

Concise Reviews: Can Mesenchymal Stromal Cells Differentiate into Corneal Cells? A Systematic Review of Published Data

et al. 2015

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The majority of stem cell therapies for corneal repair are based upon the use of progenitor cells isolated from corneal tissue, but a growing body of literature suggests a role for mesenchymal stromal cells (MSC) isolated from noncorneal tissues. While the mechanism of MSC action seems likely to involve their immuno-modulatory properties, claims have emerged of MSC transdifferentiation into corneal cells. Substantial differences in methodology and experimental outcomes, however, have prompted us to perform a systematic review of the published data. Key questions used in our analysis included: the choice of markers used to assess corneal cell phenotype, the techniques used to detect these markers, adequate reporting of controls, and tracking of MSC when studied in vivo. Our search of the literature revealed 28 papers published since 2006, with half appearing since 2012. MSC cultures established from bone marrow and adipose tissue have been best studied (22 papers). Critically, only 11 studies used appropriate markers of corneal cell phenotype, along with necessary controls. Ten out of these eleven papers, however, contained positive evidence of corneal cell marker expression by MSC. The clearest evidence is observed with respect to expression of markers for corneal stromal cells by MSC. In comparison, the evidence for MSC conversion into either corneal epithelial cells or corneal endothelial cells is often inconsistent or inconclusive. Our analysis clarifies this emerging body of literature and provides guidance for future studies of MSC differentiation within the cornea as well as other tissues. STEM CELLS 2015;33:785-791

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“…rbASCs have been used in tissue regeneration models for bone, cartilage, and cornea, but it has not been explicitly demonstrated that these stem cells are multipotent (Bahrani et al, ; De Girolamo et al, ; Ma, Bao, Cui, & Zou, ). Our results show that, like rat and human ASCs (Gimble, Katz, & Bunnell, ; Zuk, ), rbASCs are multipotent and are able to differentiate along chondrogenic, osteogenic, and adipogenic lineages.…”

Section: Discussionmentioning

confidence: 99%

Microencapsulated rabbit adipose stem cells initiate tissue regeneration in a rabbit ear defect model

Leslie

Cohen

Hyzy

et al. 2018

J Tissue Eng Regen Med

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Cell-based tissue engineering can promote cartilage tissue regeneration, but cell retention in the implant site post-delivery is problematic. Alginate microbeads containing adipose stem cells (ASCs) pretreated with chondrogenic media have been used successfully to regenerate hyaline cartilage in critical size defects in rat xiphoid suggesting that they may be used to treat defects in elastic cartilages such as the ear. To test this, we used microbeads made with low viscosity, high mannuronate medical grade alginate using a high electrostatic potential, and a calcium cross linking solution containing glucose. Microbeads containing rabbit ASCs (rbASCs) were implanted bilaterally in 3 mm critical size midcartilage ear defects of six skeletally mature male New Zealand White rabbits (empty defect; microbeads without cells; microbeads with cells; degradable microbeads with cells; and autograft). Twelve weeks post-implantation, regeneration was assessed by microCT and histology. Microencapsulated rbASCs cultured in chondrogenic media expressed mRNAs for aggrecan, Type II collagen, and Type X collagen. Histologically, empty defects contained fibrous tissue; microbeads without cells were still present in defects and were surrounded by fibrous tissue; nondegradable beads with rbASCs initiated cartilage regeneration; degradable microbeads with cells produced immature bone-like tissue, also demonstrated by microCT; and autografts appeared as normal auricular cartilage but were not fully integrated with the tissue surrounding the defect. Elastin, the hallmark of auricular cartilage, was not evident in the neocartilage. This delivery system offers the potential for regeneration of auricular cartilage, but vascularity of the treatment site and use of factors that induce elastin must be considered.

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The Graft of Autologous Adipose-Derived Stem Cells in the Corneal Stromal after Mechanic Damage

Cited by 35 publications

References 34 publications

Progress in corneal wound healing

Progress in corneal wound healing

Concise Reviews: Can Mesenchymal Stromal Cells Differentiate into Corneal Cells? A Systematic Review of Published Data

Microencapsulated rabbit adipose stem cells initiate tissue regeneration in a rabbit ear defect model

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