Mesenchymal stromal cells for ocular surface repair

Al-Jaibaji, Olla; Swioklo, Stephen; Connon, Che J.

doi:10.1080/14712598.2019.1607836

Cited by 16 publications

(9 citation statements)

References 87 publications

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“…Thus, the co-cultivation of LEPC with LMSC/LM could represent an improved strategy to generate cell transplants for patients suffering from limbal stem cell deficiency [ 10 , 11 ]. In addition, both LMSC and LM were shown to have potent immunomodulatory, anti-inflammatory and anti-angiogenic properties, making them attractive tools for clinical use [ 9 , 12 , 13 , 14 ]. To date, research on freshly isolated LMSC or LM, which may closely resemble the LNC in vivo, has been hampered by the lack of an efficient and fast protocol for isolating these cells as pure populations.…”

Section: Introductionmentioning

confidence: 99%

Efficient Isolation and Functional Characterization of Niche Cells from Human Corneal Limbus

Polisetti

Sharaf

Schlötzer‐Schrehardt

et al. 2022

IJMS

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The fate decision of limbal epithelial progenitor cells (LEPC) at the human corneal limbus is determined by the surrounding microenvironment with limbal niche cells (LNC) as one of its essential components. Research on freshly isolated LNC which mainly include limbal mesenchymal stromal cells (LMSC) and limbal melanocytes (LM) has been hampered by a lack of efficient protocols to isolate and purify these cells. We devised a protocol for rapid retrieval of pure LMSC, LM and LEPC populations by collagenase digestion of limbal tissue and subsequent fluorescence-activated cell sorting (FACS) using antibodies against CD90 and CD117. The sorted cells were characterized by immunophenotyping and functional assays. The effects of LMSC and LM on LEPC were studied in 3D co-cultures and LEPC differentiation status was assessed by immunohistochemistry. Enzymatic digestion and flow sorting yielded pure populations of LMSC (CD117−CD90+), LM (CD117+CD90−), and LEPC (CD117−CD90−). The LMSC exhibited self-renewal capacity (55.0 ± 4.6 population doublings), expressed mesenchymal stem cell markers (CD73, CD90, CD105, and CD44), and transdifferentiated to adipocytes, osteocytes, or chondrocytes. The LM exhibited self-renewal capacity and sustained melanin production. The sorted LEPC expressed epithelial progenitor markers (CK14, CK19, and CK15) and showed a colony-forming ability. Co-cultivation of LMSC and LM with LEPC resulted in a 4–5-layered stratified epithelium and supported the preservation of a LEPC phenotype, as reflected by increased p63+ and Ki67+ cells and decreased CK12+ cells compared with LEPC monocultures. A highly efficient isolation of pure LM, LMSC, and LEPC populations from a single preparation may allow for direct transcriptomic and proteomic profiling as well as functional studies on native unpassaged LNC, which can be considered as proper equivalents of LNC in vivo. The developed biomimetic 3D co-culture method could provide an experimental model for investigating the functional role of LNC in the limbal stem cell niche.

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Section: Introductionmentioning

confidence: 99%

Efficient Isolation and Functional Characterization of Niche Cells from Human Corneal Limbus

Polisetti

Sharaf

Schlötzer‐Schrehardt

et al. 2022

IJMS

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“…Current treatments often include corneal transplantation if the visual axis is affected, which has limitations due to donor availability and compatibility. To restore corneal transparency and integrity, Ad-MSCs therapy has been investigated [ 35 , 36 , 37 , 38 , 39 ]. Using clinical and animal studies, Ad-MSCs therapy has recently proven to be a promising method used in corneal reconstruction with multiple treatment approaches [ 40 , 41 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Hypothermically Stored Adipose-Derived Mesenchymal Stromal Cell Alginate Bandages Facilitate Use of Paracrine Molecules for Corneal Wound Healing

Al-Jaibaji

Swioklo

Shortt³

et al. 2020

IJMS

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Adipose-derived mesenchymal stromal cells (Ad-MSCs) may alleviate corneal injury through the secretion of therapeutic factors delivered at the injury site. We aimed to investigate the therapeutic factors secreted from hypothermically stored, alginate-encapsulated Ad-MSCs’ bandages in in vitro and in vivo corneal wounds. Ad-MSCs were encapsulated in 1.2% w/v alginate gels to form bandages and stored at 15 °C for 72 h before assessing cell viability and co-culture with corneal scratch wounds. Genes of interest, including HGF, TSG-6, and IGF were identified by qPCR and a human cytokine array kit used to profile the therapeutic factors secreted. In vivo, bandages were applied to adult male mice corneas following epithelial debridement. Bandages were shown to maintain Ad-MSCs viability during storage and able to indirectly improve corneal wound healing in vivo. Soluble protein concentration and paracrine factors such as TSG-6, HGF, IL-8, and MCP-1 release were greatest following hypothermic storage. In vivo, Ad-MSCs bandages-treated groups reduced immune cell infiltration when compared to untreated groups. In conclusion, bandages were shown to maintain Ad-MSCs ability to produce a cocktail of key therapeutic factors following storage and that these soluble factors can improve in vitro and in vivo corneal wound healing.

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“…Over the last few years, the field of cell-based therapies to treat both DED and LSCD pathologies has undergone great development. Experimental and clinical MSC-based therapies have increased in the last decade due to their immunomodulatory and anti-inflammatory properties, their capability to migrate to injured and inflamed tissues, and their capacity to differentiate into corneal epithelial cells [ 82 ].…”

Section: Corneal Epithelium Adsc Regeneration: Preclinical and Clinic...mentioning

confidence: 99%

Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells

Barrio

Mata

Miguel

et al. 2022

Cells

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Adipose-derived stem cells are a subtype of mesenchymal stem cell that offers the important advantage of being easily obtained (in an autologous manner) from low invasive procedures, rendering a high number of multipotent stem cells with the potential to differentiate into several cellular lineages, to show immunomodulatory properties, and to promote tissue regeneration by a paracrine action through the secretion of extracellular vesicles containing trophic factors. This secretome is currently being investigated as a potential source for a cell-free based regenerative therapy for human tissues, which would significantly reduce the involved costs, risks and law regulations, allowing for a broader application in real clinical practice. In the current article, we will review the existing preclinical and human clinical evidence regarding the use of such adipose-derived mesenchymal stem cells for the regeneration of the three main layers of the human cornea: the epithelium (derived from the surface ectoderm), the stroma (derived from the neural crest mesenchyme), and the endothelium (derived from the neural crest cells).

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Mesenchymal stromal cells for ocular surface repair

Cited by 16 publications

References 87 publications

Efficient Isolation and Functional Characterization of Niche Cells from Human Corneal Limbus

Efficient Isolation and Functional Characterization of Niche Cells from Human Corneal Limbus

Hypothermically Stored Adipose-Derived Mesenchymal Stromal Cell Alginate Bandages Facilitate Use of Paracrine Molecules for Corneal Wound Healing

Corneal Regeneration Using Adipose-Derived Mesenchymal Stem Cells

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