A long-term retaining molecular coating for corneal regeneration.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang Y
PROVIDER: S-EPMC8114076 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose:To assess the stemness and regenerative potential of cryopreserved corneal stromal stem cells (cryo-CSSCs) after long-term storage. We also used the secretome from these cells to observe the effect on wound-healing capacity of corneal fibroblasts and on the expression of fibrotic markers during wound healing. Methods:CSSCs were obtained from three donors and stored in liquid nitrogen for approximately 10 years. Post thaw, cryo-CSSCs were characterized for stemness using phenotypic and genotypic markers along with colony-forming efficiency and three-dimensional spheroid formation. Multilineage differentiation was observed by differentiation into osteocytes, adipocytes, neural cells, and keratocytes. Secretome was harvested by culturing cryo-CSSCs in log phase. Wound-healing capacity was observed by live-cell time-lapse microscopy. Statistical analysis was done using 1-way ANOVA and Tukey posttest. Results:CSSCs displayed good viability post thaw and showed >90% expression of stem cell markers CD90, CD73, CD105, STRO1, and CD166. cryo-CSSCs also expressed stem cell genes OCT4, KLF4, and ABCG2, and could also form colonies and three-dimensional spheroids. Multipotency assessment showed that all three cryo-CSSCs could differentiate into osteocytes, adipocytes, neural cells, as shown by ?-III tubulin and neurofilament antibody staining and corneal keratocytes as observed by staining for Kera C, J19, and collagen V antibodies. The secretome derived from these three populations could promote the wound healing of corneal fibroblasts and reduce the expression of fibrotic markers SPARC and fibronectin. Conclusions:CSSCs maintained their stemness and multipotency after long-term storage, and secretome derived from these cells can be of paramount importance for corneal regeneration and prevention of fibrosis.
| S-EPMC6059729 | biostudies-literature
Project description:Purpose:To investigate the change in corneal toricity and associated refractive astigmatism after discontinuation of long-term orthokeratology (ortho-k) lens wear. Methods:This study investigated 136 subjects aged between 6 and 14 (9.1 ± 1.5) years old at the commencement of ortho-k treatment, who had been undergoing overnight ortho-k treatment for 24 to 72 (37.4 ± 11.9) months. Corneal refractive power and manifest refraction were measured and compared before ortho-k and 1 month after discontinuation of ortho-k lens wear. Changes in corneal curvature were analyzed. Corneal curvature data from a historical longitudinal study were used as control. Results:Compared to pre-ortho-k values, the corneal curvature became significantly flatter in the flatter meridian (-0.22 ± 0.27 D, P < 0.001) and steeper in the steeper meridian (0.06 ± 0.34 D, P=0.032) after cessation of ortho-k lens wear, resulting in a significant increase in corneal toricity (0.28 ± 0.43 D, P < 0.001), which is associated with an increase in refractive astigmatism (0.57 ± 0.57 D, r=0.465, P < 0.001). The amount of residual corneal flattening in the flatter meridian is significantly affected by the length of ortho-k treatment (t=-2.965, P=0.004) and the baseline age of subject (t=-2.841, P=0.005), but not by the baseline spherical or cylindrical refractive error (both P > 0.05). In the historical control group, there is no significant change in the corneal curvature over two years in children wearing spectacle lenses (both meridians, P > 0.05). Change of corneal toricity was more significant in the ortho-k group than in the spectacle control group (P=0.001). Conclusions:Long-term ortho-k lens wear increases corneal toricity after discontinuation of the treatment, which is associated with an increase in refractive astigmatism. A more pronounced change in corneal toricity was found in subjects who were younger to start ortho-k and have been in a longer period of treatment. This trial is registered with http://www.chictr.org.cn (ChiCTR-TNRC-11001210).
| S-EPMC6218724 | biostudies-literature
Project description:Myopia is very prevalent worldwide, especially among Asian populations. Orthokeratology is a proven intervention to reduce myopia progression. The current study investigated association between baseline corneal biomechanics and orthokeratology responses, and changes of corneal biomechanics from long-term orthokeratology. We fitted 59 adult subjects having myopia between -4.00D to -5.00D with overnight orthokeratology. Corneal biomechanics was measured through dynamic bidirectional corneal applanation (in terms of corneal hysteresis, CH and corneal resistance factor, CRF) and corneal indentation (in terms of corneal stiffness, S and tangent modulus, E). Subjects with poor orthokeratology responses had lower E (mean 0.474?MPa) than subjects with good orthokeratology responses (mean 0.536?MPa). Successful orthokeratology for 6 months resulted in reducing CH (reduced by 5.8%) and CRF (reduced by 8.7%). Corneal stiffness was stable, but E showed an increasing trend. Among subjects with successful orthokeratology, a higher baseline S resulted in greater myopia reduction (Pearson correlation coefficient, r?=?0.381, p?=?0.02).
| S-EPMC6715748 | biostudies-literature
Project description:Human pluripotent stem cells (hPSCs) hold great promise for the treatment of various human diseases. However, their therapeutic benefits and mechanisms for treating corneal endothelial dysfunction remain undefined. Here, we developed a therapeutic regimen consisting of the combination of hPSC-derived corneal endothelial precursors (CEPs) with nicotinamide (NAM) for effective treatment of corneal endothelial dysfunction. In rabbit and nonhuman primate models, intracameral injection of CEPs and NAM achieved long-term recovery of corneal clarity and thickness, similar with the therapeutic outcome of cultured human corneal endothelial cells (CECs). The transplanted human CEPs exhibited structural and functional integration with host resident CECs. However, the long-term recovery relied on the stimulation of endogenous endothelial regeneration in rabbits, but predominantly on the replacing function of transplanted cells during the 3-year follow-up in nonhuman primates, which resemble human corneal endothelium with limited regenerative capacity. Mechanistically, NAM ensured in vivo proper maturation of transplanted CEPs into functional CECs by preventing premature senescence and endothelial-mesenchymal transition within the TGF-β-enriched aqueous humor. Together, we provide compelling experimental evidence and mechanistic insights of simultaneous delivery of CEPs and NAM as a potential approach for treating corneal endothelial dysfunction.
| S-EPMC8718141 | biostudies-literature
Project description:Background Retention can be difficult in longitudinal trials, especially among minoritized groups and individuals with low socioeconomic status (SES) who may experience more barriers to research participation. Organized retention strategies may help; however, limited research has reported on this in detail. Methods We employed several strategies throughout a 15-month randomized controlled trial to encourage retention among a diverse sample of adults with type 2 diabetes. Participants were randomized to receive mobile health support for diabetes self-care for 12 months or an attention control. Participants completed assessments at 3, 6, 12, and 15 months post-baseline. We used three main categories of retention strategies: flexibility in participation (e.g., multiple methods for data collection), communication (e.g., tracking contacts), and community building (e.g., study branding, newsletters). We monitored participants' use of strategies and examined associations between participant characteristics and retention. Results Retention remained high (≥90%) at each follow-up assessment. Participants used various methods for survey completion: online (34%), in-person (31%), and mail (30%). Most (73%) used a mail-in A1c kit at least once. Multiple completion methods were important for retaining minoritized and lower SES participants who completed assessments in-person more frequently. Communication also facilitated retention; 39% of participants used a study Helpline and tracking systems helped maintain contact. Conclusions Retaining disadvantaged patients in clinical trials is necessary so findings generalize to and can benefit these populations. Retention strategies that reduce barriers to participation and engage participants and community partners can be successful. Future studies should assess the impact of retention strategies.
| S-EPMC8172486 | biostudies-literature
Project description:Several species of sacoglossan sea slugs possess the incredible ability to sequester chloroplasts from the algae they consume. These "photosynthetic animals" incorporate stolen chloroplasts, called kleptoplasts, into the epithelial cells of tubules that extend from their digestive tracts throughout their bodies. The mechanism by which these slugs maintain functioning kleptoplasts in the absence of an algal nuclear genome is unknown. Here, we report a draft genome of the sacoglossan slug Elysia crispata morphotype clarki, a morphotype native to the Florida Keys that can retain photosynthetically active kleptoplasts for several months without feeding. We used a combination of Oxford Nanopore Technologies long reads and Illumina short reads to produce a 786-Mb assembly (N50 = 0.459 Mb) containing 68,514 predicted protein-coding genes. A phylogenetic analysis found no evidence of horizontal acquisition of genes from algae. We performed gene family and gene expression analyses to identify E. crispata genes unique to kleptoplast-containing slugs that were more highly expressed in fed versus unfed developmental life stages. Consistent with analyses in other kleptoplastic slugs, our investigation suggests that genes encoding lectin carbohydrate-binding proteins and those involved in regulation of reactive oxygen species and immunity may play a role in kleptoplast retention. Lastly, we identified four polyketide synthase genes that could potentially encode proteins producing UV- and oxidation-blocking compounds in slug cell membranes. The genome of E. crispata is a quality resource that provides potential targets for functional analyses and enables further investigation into the evolution and mechanisms of kleptoplasty in animals.
| S-EPMC10700116 | biostudies-literature
Project description:Objective:To report long-term clinical outcomes of gamma-irradiated corneal lenticules in partial and full-thickness keratoplasty. Methods and Analysis:This multicentre, retrospective case series includes 23 patients who underwent surgery at three centres (India, Guatemala, and USA) between May 2009 and March 2018. The main outcome measures were epithelialization and retention for therapeutic keratoplasty and best spectacle-corrected visual acuity (BSCVA) for optical keratoplasty. Results:Patients were categorised according to primary aetiology requiring corneal transplantation: non-inflammatory conditions, infectious keratitis and sterile keratolysis. Nine patients with non-inflammatory conditions underwent anterior lamellar keratoplasty (n=7) and Boston type 1 keratoprosthesis (n=2). All nine grafts remained intact and epithelialized during follow-up (median 24 months). In the seven patients who underwent anterior keratoplasty, the graft stayed optically clear during follow-up (median 12 months), with BSCVA between 20/20 and 20/40 in all but one patient who developed cataract. Nine patients with severe infectious keratitis had emergency patch grafting. Six of those grafts epithelialized and remained intact over a median of 30 months, providing tectonic support until optical keratoplasty with fresh tissue could be performed. Three grafts had recurrent infectious keratitis 1-3 months postoperatively, two of which underwent tectonic keratoplasty with fresh tissue which also eventually became infected during follow-up. In five additional patients with sterile keratolysis who underwent lamellar patch graft, two grafts remained intact during follow-up (median 36 months). Two patients had recurrent corneal melt within 1 month, and both had subsequent corneal surgery with fresh tissue which also failed. There were no donor-related complications. Conclusion:Gamma-irradiated sterile corneal stromal lenticules can be considered as a viable alternative to fresh tissue in various clinical settings.
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Project description:Recent data suggest that therapy-resistant quiescent cancer stem cells (qCSCs) are the source of relapse in colon cancer. Here, using colon cancer patient-derived organoids and xenografts, we identify rare long-term label-retaining qCSCs that can re-enter the cell cycle to generate new tumors. RNA sequencing analyses demonstrated that these cells display the molecular hallmarks of quiescent tissue stem cells, including expression of p53 signaling genes, and are enriched for transcripts common to damage-induced quiescent revival stem cells of the regenerating intestine. In addition, we identify negative regulators of cell cycle, downstream of p53, that we show are indicators of poor prognosis and may be targeted for qCSC abolition in both p53 wild-type and mutant tumors. These data support the temporal inhibition of downstream targets of p53 signaling, in combination with standard-of-care treatments, for the elimination of qCSCs and prevention of relapse in colon cancer.
| S-EPMC8185225 | biostudies-literature
Project description:Trapping air at the solid-liquid interface is a promising strategy for reducing frictional drag and desalting water, although it has thus far remained unachievable without perfluorinated coatings. Here, we report on biomimetic microtextures composed of doubly reentrant cavities (DRCs) and reentrant cavities (RCs) that can enable even intrinsically wetting materials to entrap air for long periods upon immersion in liquids. Using SiO2/Si wafers as the model system, we demonstrate that while the air entrapped in simple cylindrical cavities immersed in hexadecane is lost after 0.2 s, the air entrapped in the DRCs remained intact even after 27 days (~106 s). To understand the factors and mechanisms underlying this ten-million-fold enhancement, we compared the behaviors of DRCs, RCs and simple cavities of circular and non-circular shapes on immersion in liquids of low and high vapor pressures through high-speed imaging, confocal microscopy, and pressure cells. Those results might advance the development of coating-free liquid repellent surfaces.
| S-EPMC6127334 | biostudies-literature
Project description:Corneal transplantation is the most effective clinical treatment for corneal defects, but it requires precise size of donor corneas, surgical sutures, and overcoming other technical challenges. Postoperative patients may suffer graft rejection and complications caused by sutures. Ophthalmic glues that can long-term integrate with the corneal tissue and effectively repair the focal corneal damage are highly desirable. Herein, a hybrid hydrogel consisting of porcine decellularized corneal stroma matrix (pDCSM) and methacrylated hyaluronic acid (HAMA) was developed through a non-competitive dual-crosslinking process. It can be directly filled into corneal defects with various shapes. More importantly, through formation of interpenetrating network and stable amide bonds between the hydrogel and adjacent tissue, the hydrogel manifested excellent adhesion properties to achieve suture-free repair. Meanwhile, the hybrid hydrogel not only preserved bioactive components from pDCSM, but also exhibited cornea-matching transparency, low swelling ratio, slow degradation, and enhanced mechanical properties, which was capable of withstanding superhigh intraocular pressure. The combinatorial hydrogel greatly improved the poor cell adhesion performance of HAMA, supported the viability, proliferation of corneal cells, and preservation of keratocyte phenotype. In a rabbit corneal stromal defect model, the experimental eyes treated with the hybrid hydrogel remained transparent and adhered intimately to the stroma bed with long-term retention, accelerated corneal re-epithelialization and wound healing. Giving the advantages of high bioactivity, low-cost, and good practicality, the dual-crosslinked hybrid hydrogel served effectively for long-term suture-free treatment and tissue regeneration after corneal defect.
| S-EPMC9234351 | biostudies-literature