Human corneal stromal stem cells express anti-fibrotic microRNA-29a and 381-5p – A robust cell selection tool for stem cell therapy of corneal scarring

Yam, Gary Hin‐Fai; Yang, Tsung‐Ying; Geary, Moira L.; Santra, Mithun; Funderburgh, Martha L.; Rubin, Elizabeth; Du, Yiqin; Sahel, J; Jhanji, Vishal; Funderburgh, James L.

doi:10.1016/j.jare.2022.05.008

Cited by 11 publications

(11 citation statements)

References 57 publications

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“…Genes belonging to signaling pathways such as Wnt (211 DEGs), TGF-β (85 DEGs), stem cell (23 DEGs), and wound healing pathways (254 DEGs) were also obtained ( Supplementary Figure S1, and Supplementary Tables S5 and S6 ). Many studies have proven the anti-inflammatory and immunomodulatory properties of the LMSCs [ 70 , 76 , 77 , 82 ]. The findings of the current study also support the anti-inflammatory nature of these cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling of Human Limbus-Derived Stromal/Mesenchymal Stem Cells—Novel Mechanistic Insights into the Pathways Involved in Corneal Wound Healing

Tavakkoli

Damala

Koduri

et al. 2022

IJMS

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Limbus-derived stromal/mesenchymal stem cells (LMSCs) are vital for corneal homeostasis and wound healing. However, despite multiple pre-clinical and clinical studies reporting the potency of LMSCs in avoiding inflammation and scarring during corneal wound healing, the molecular basis for the ability of LMSCs remains unknown. This study aimed to uncover the factors and pathways involved in LMSC-mediated corneal wound healing by employing RNA-Sequencing (RNA-Seq) in human LMSCs for the first time. We characterized the cultured LMSCs at the stages of initiation (LMSC−P0) and pure population (LMSC−P3) and subjected them to RNA-Seq to identify the differentially expressed genes (DEGs) in comparison to native limbus and cornea, and scleral tissues. Of the 28,000 genes detected, 7800 DEGs were subjected to pathway-specific enrichment Gene Ontology (GO) analysis. These DEGs were involved in Wnt, TGF-β signaling pathways, and 16 other biological processes, including apoptosis, cell motility, tissue remodeling, and stem cell maintenance, etc. Two hundred fifty-four genes were related to wound healing pathways. COL5A1 (11.81 ± 0.48) and TIMP1 (20.44 ± 0.94) genes were exclusively up-regulated in LMSC−P3. Our findings provide new insights involved in LMSC-mediated corneal wound healing.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling of Human Limbus-Derived Stromal/Mesenchymal Stem Cells—Novel Mechanistic Insights into the Pathways Involved in Corneal Wound Healing

Tavakkoli

Damala

Koduri

et al. 2022

IJMS

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“…They showed that the EV treatment was effective in preventing neutrophil infiltration, reducing fibrosis marker expression, and recovery of the stromal organization. Our group recently characterized these CSSC-derived EVs using Nanostring microRNA profiler platform (Human v3 miRNA assay) and identified the presence of anti-fibrosis microRNAs hasa-miR-29a and miR-381-5p) in the Evs cargo [ 112 ]. In vitro, the expression of these two microRNAs reduced the lipopolysaccharide-stimulated M1 response of mouse macrophages and suppressed the TGFβ1-caused fibrotic reaction of human primary CSKs.…”

Section: Cell-free Approach For Stromal Wound Healing and Regenerationmentioning

confidence: 99%

Regenerative Therapy for Corneal Scarring Disorders

Chandran,

Santra,

Rubin

et al. 2024

Biomedicines

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The cornea is a transparent and vitally multifaceted component of the eye, playing a pivotal role in vision and ocular health. It has primary refractive and protective functions. Typical corneal dysfunctions include opacities and deformities that result from injuries, infections, or other medical conditions. These can significantly impair vision. The conventional challenges in managing corneal ailments include the limited regenerative capacity (except corneal epithelium), immune response after donor tissue transplantation, a risk of long-term graft rejection, and the global shortage of transplantable donor materials. This review delves into the intricate composition of the cornea, the landscape of corneal regeneration, and the multifaceted repercussions of scar-related pathologies. It will elucidate the etiology and types of dysfunctions, assess current treatments and their limitations, and explore the potential of regenerative therapy that has emerged in both in vivo and clinical trials. This review will shed light on existing gaps in corneal disorder management and discuss the feasibility and challenges of advancing regenerative therapies for corneal stromal scarring.

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“…They were reported to control corneal tissue inflammation and fibrosis [17][18][19]. Our recent study has identified that 2 specific miRNAs (miR-29a and 381-5p), delivered via CSSC-derived EV, could downregulate stromal inflammation and fibrotic onset after corneal injury in mice, leading to a scarless stromal ECM remodeling [20].…”

Section: Introductionmentioning

confidence: 99%

Combined Therapy Using Human Corneal Stromal Stem Cells and Quiescent Keratocytes to Prevent Corneal Scarring after Injury

Jhanji

Santra

Riau

et al. 2022

IJMS

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Corneal blindness due to scarring is conventionally treated by corneal transplantation, but the shortage of donor materials has been a major issue affecting the global success of treatment. Pre-clinical and clinical studies have shown that cell-based therapies using either corneal stromal stem cells (CSSC) or corneal stromal keratocytes (CSK) suppress corneal scarring at lower levels. Further treatments or strategies are required to improve the treatment efficacy. This study examined a combined cell-based treatment using CSSC and CSK in a mouse model of anterior stromal injury. We hypothesize that the immuno-regulatory nature of CSSC is effective to control tissue inflammation and delay the onset of fibrosis, and a subsequent intrastromal CSK treatment deposited collagens and stromal specific proteoglycans to recover a native stromal matrix. Using optimized cell doses, our results showed that the effect of CSSC treatment for suppressing corneal opacities was augmented by an additional intrastromal CSK injection, resulting in better corneal clarity. These in vivo effects were substantiated by a further downregulated expression of stromal fibrosis genes and the restoration of stromal fibrillar organization and regularity. Hence, a combined treatment of CSSC and CSK could achieve a higher clinical efficacy and restore corneal transparency, when compared to a single CSSC treatment.

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Human corneal stromal stem cells express anti-fibrotic microRNA-29a and 381-5p – A robust cell selection tool for stem cell therapy of corneal scarring

Cited by 11 publications

References 57 publications

Transcriptomic Profiling of Human Limbus-Derived Stromal/Mesenchymal Stem Cells—Novel Mechanistic Insights into the Pathways Involved in Corneal Wound Healing

Transcriptomic Profiling of Human Limbus-Derived Stromal/Mesenchymal Stem Cells—Novel Mechanistic Insights into the Pathways Involved in Corneal Wound Healing

Regenerative Therapy for Corneal Scarring Disorders

Combined Therapy Using Human Corneal Stromal Stem Cells and Quiescent Keratocytes to Prevent Corneal Scarring after Injury

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