Development and validation of an in vitro permeation test method for rectal mesalamine suppositories.

Non-viral strategies for transfection of the corneal endothelium.

Toward the ideal corneal construct: Design principles, biofabrication strategies, and translational challenges in 3D bioprinting.

Recombinant dimeric PICK1 peptide inhibitors for long-term relief of chronic pain by AAV therapeutics.

Advances in Differentiation of Induced Pluripotent Stem Cell-Derived Corneal Endothelial Cells: Pathway Insights and Evaluation of Characterization Practices.

Anita Law: Effect of Its Implementation on Tissue and Organ Donation and Transplant in Paraguay.

Primary dopaminergic cell transplantation is a potential therapeutic strategy for Parkinson's disease. However, the procedure commonly involves placing donor neurons heterotopically into the host striatum. To gain insights into the potential to reform circuitry between the substantia nigra and striatum, a sagittal explant system, including the striatum, medial forebrain bundle (MFB) and ventral mesencephalon (VM), was generated from postnatal rats. This exvivo system provided a platform to test the potential for heterotopic or homotopic grafts of whole embryonic day 14 (E14) rat VM or sub-dissected regions of the A9 or A10 cell groups to reform midbrain dopaminergic circuitry. Results showed that homotopically placed whole VM tissue and sub-dissected A10 donor tissue were able to extend tyrosine hydroxylase+ (TH+) projections along the full rostro-caudal extent of the MFB. However, homotopically grafted A9 dopamine neurons showed little capacity to extend TH+ neurites beyond the graft region. In addition, heterotopic placement of A9 tissue adjacent to the host striatum revealed selective infiltration of TH+ projections into the dorsal striatum, where they displayed functional electrophysiological responses in host striatal neurons. This was in opposition to A10 heterotopic grafts, where TH+ projections were more random with no evidence of synaptic coupling in the host. Such results illustrate the fundamental utility of this system for exploring dopaminergic circuitry reconstruction exvivo and indicate that the reformation of nigrostriatal circuitry may be limited for the A9 group in isolation, but that the A10 neurons can project along the full extent of the MFB.

Corneal perforations necessitate prompt surgical intervention to restore globe integrity and mitigate the risk of irreversible vision loss. Larger corneal perforations often require more complex surgical strategies, including tectonic patch grafting or penetrating keratoplasty. However, limited availability of donor tissue presents significant challenges in meeting urgency of these cases. We describe an ab interno technique approach for corneal perforation repair, using off-the-shelf human cornea as an alternative viable surgical treatment. The surgery was performed at a tertiary center in the United Kingdom, where Halo (VisionGift, Portland, OR) cornea, made from preserved human corneal tissue, was used for perforation repair. The tissue meets Food and Drug Administration and United Kingdom regulatory standards. An 89-year-old woman presented with a painful, red left eye associated with significant vision loss. She had a complex ocular history, including herpes zoster ophthalmicus keratitis. On examination, the left eye visual acuity was reduced to hand motion with an inferior corneal perforation. Surgical management involved placement of the Halo cornea disc internally over the defect with gas tamponade. At 1 week, the patient's left eye vision had improved to 6/24, with intraocular pressure of 10 mm Hg. Nine months postsurgery, the left eye's visual acuity improved to 6/9, with no graft detachment, inflammation, or vascularization observed. This case highlights the successful use of a Halo cornea graft for the management of a large peripheral corneal perforation in a patient with complex ocular pathology. This technique would be of particular interest to ophthalmologists who manage corneal perforations.

A suitable tissue-engineered equivalent is necessary to support cultured cells for cell therapy transplantation, thereby alleviating the increasing demand for donor tissue. A compressed collagen I hydrogel, Real Architecture For 3D Tissue (RAFT), was introduced to substitute native corneal stroma for supporting endothelial cell growth as an extracellular cellular matrix (ECM) tissue equivalent. Here, the RAFT's mechanical properties and transparency were optimized to tailor for designing a corneal endothelium transplantation graft. Meanwhile, the gene and protein expression of ZO-1, Na/K ATPase, and N-Cadherin were used to investigate the impact of mechanical properties on cell behavior. The results showed that increasing the collagen concentration and reducing the initial loading volume could generate a stiffer, thinner, and more transparent RAFT. Staining results showed that porcine corneal endothelial cells (PCECs) remained alive, forming a high cell density monolayer with ZO-1 and Na/K ATPase expressions on various stiffnesses of RAFTs. Gene and protein expression results showed that PCECs could grow on various stiffnesses of RAFTs (elastic modulus ranged from 1.17 ± 0.11 to 2.08 ± 0.14 MPa), expressing ZO-1, Na/K ATPase, and N-Cadherin. In short, RAFTs fabricated with 0.4 of 5 mg/mL collagen I shared similar optical and mechanical properties to the native cornea, with a thickness of 73.67 ± 1.70 μm, a stiffness of 0.40 ± 0.03 MPa, an elastic modulus of 1.17 ± 0.07 MPa, and light transmittance of 60.71% ± 1.17%. This is an ideal tissue-engineered cell carrier suitable for developing a cell-seeded RAFT graft for cell therapy.

The purpose of the paper is to study the utilization profile of donor corneas with death-to-retrieval time (DRT) >12 h in the Indian population and to assess the safety of endothelial keratoplasty using such corneas. This retrospective study (Jan 2018-June 2023) analyzed eye bank records of donor corneas with DRT ≥12 h. The primary outcome assessed was the utilization rate across different keratoplasties. Secondary outcomes included records of endothelial cell density (ECD) of donor tissue. Records of outcomes of endothelial keratoplasty using such corneas in the form of postoperative recorded visual acuity, graft clarity, postoperative ECD, signs of graft infection, and failure were evaluated. Out of 333 donor corneas, 75.68% were suitable for transplantation, 21.3% were allocated for research, and 3% were unfit. Among transplantable corneas, 42.04% were used for optical penetrating keratoplasty (PK), 15.9% for Descemet stripping automated endothelial keratoplasty, 9.9% for therapeutic PK, 4.5% for deep anterior lamellar keratoplasty, 1.5% for patch grafts, 1.2% for tectonic PK, and 0.3% each in Descemet membrane endothelial keratoplasty and tuck in lamellar keratoplasty. Mean ECD for endothelial keratoplasty suitable corneas was 2633 ± 291 cells/mm². Minimum 6 months follow-up records of endothelial keratoplasty showed that 91% achieved best-corrected visual acuity ≥6/18 and ≥6/12 in 60%. The maximum follow-up period was 4 years. Mean ECD declined to 1857.02 ± 133.11 cells/mm² ( P < 0.0001). Graft rejection was recorded in 13.34%, elevated intraocular pressure in 18%, and graft infections in none. Properly screened corneas with DRT >12 h lead to successful endothelial keratoplasty outcomes. Traditional DRT limits should be re-evaluated, especially in regions with a shortage of donor cornea. Preservation quality, ECD, and preoperative assessment are critical.

Protocol for culturing healthy primary endothelial cells isolated from research-grade human corneoscleral donor tissue.

Abstract Patient-derived tumor organoids have emerged as a promising translational model for oncology drug development. However, its utility has been limited by restricted access to patient-derived materials and insufficient donor-related data such as clinical records. Here, we report the establishment of the Samsung Organoids, a GxP-based, standardized patient-derived organoid designed to support data-driven cancer drug development. All organoids were generated and processed by GxP-qualified personnel under rigorously controlled and fully documented procedures, ensuring reproducibility, traceability, and regulatory readiness. Each organoid line is linked to clinical information of the corresponding donor and multi-omics data both original tumor tissues and derived organoids. Comparative analyses demonstrated high concordance of mutational profiles and gene expression patterns between tumor tissues and matched organoids, confirming preservation of the patient-specific characteristics. To examine the responsiveness of organoids to various drugs including small molecules and ADCs, we performed high-throughput drug screening combined with high-content imaging. Drug responsiveness data revealed substantial inter-patient heterogeneity, enabling classification of organoids into distinct groups. Further, we identified particular gene expression signatures by cross-group comparison, demonstrating explanation of different drug sensitivity between organoids. Conclusively, by integrating patient clinical information with genomic/genetic alterations, transcriptomic signatures, and functional drug response data, the Samsung Organoids provides translational insights into determinants of therapeutic sensitivity and resistance, helping successful cancer drug development such as drug candidate selection, biomarker discovery, and preclinical decision-making. Citation Format: Minhyung Lee, Sekyu Oh, Seongju Jeong, Sung Min Ha, Chihah Moon, Nayoun Choi, Yoonhyeok Kwon, Seahee Kim, Sangmyung Lee, Brian Hosung Min. Samsung Organoids: A GxP-based drug screening leveraging patient-derived tumor organoids platform accompanied with clinical records and multi-omics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB397.

Classical hematoxylin and eosin (H&E) staining enables review of tissue morphology but lacks information regarding the molecular state of cells. Immunohistochemical (IHC) techniques label specific proteins in tissue, allowing differentiation of relevant structures that may go undetectable in H&E. However, the IHC process is complex, expensive, and time-consuming, especially for multiplex IHC (mIHC) limiting its use in large cohorts. Stain conversion of H&E to IHC using generative artificial intelligence models such as generative adversarial networks (GANs) represent one solution to this problem. However, GANs are unstable during out of distribution sampling and are prone to hallucinations or mode collapse, limiting their accuracy in challenging image conversion tasks. To address this, the field has recently turned to diffusion models. Here, we introduce Schrödinger-bridge for Multiplex ImmunoLabel Estimation (SMILE). Unlike conventional diffusion models that map from source to target through an intermediate Gaussian noise, Schrödinger-bridge diffusion models skip this step and have been shown to better preserve structures during image translation. To test the performance of SMILE, we generated a large cohort of high-fidelity H&E-mIHC image pairs from pancreatic organ donors, targeting insulin, glucagon, and CD3. Our dataset well-sampled across type-1 diabetes status, pancreas anatomical location, age, and sex. Using this cohort, we demonstrate the superiority of SMILE compared to GANs via a comprehensive evaluation framework incorporating texture, distribution, and antibody-specific metrics, as well as blinded pathologist reviews. We further confirmed the ability of SMILE to generate accurate mIHC images from H&Es generated at an external site, to perform whole slide image conversion, and to generate realistic three-dimensional maps of the pancreatic islets in non-diabetic, auto-antibody positive, and type-1 diabetic donor tissue. Finally, we performed stain conversion of paired H&E to HER2 and Ki67 images in breast cancer, confirming the superiority of SMILE in diverse stain conversion applications. Collectively, this framework provides a scalable pipeline for high-throughput proteomic inference from archival H&Es, providing transformative potential for pancreatic research and digital pathology.

Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires a microenvironment that preserves cell viability, phenotype, and barrier integrity. Conventional culture substrates often lack physiological relevance or rely on animal-derived components, limiting translational applicability. In this study, we evaluated nanofibrillar cellulose (NFC) hydrogel (GrowDex®) as a xeno-free scaffold for primary human nasal epithelial cells (NECs). NECs isolated from healthy donor tissue were characterized by immunofluorescence and qPCR for basal, goblet, and ciliated cell markers. Cells embedded in NFC were assessed for viability, cytotoxicity, epithelial morphology, and barrier function. Transepithelial electrical resistance (TEER) and FITC-dextran permeability assays were used to quantify barrier integrity and compared with collagen- and polylysine-based controls. NECs cultured in NFC maintained high viability, stable epithelial morphology, and preserved subtype-specific marker expression without detectable cytotoxicity. NFC-supported cultures demonstrated enhanced barrier formation, indicated by higher TEER values and reduced paracellular permeability relative to controls, and sustained structural integrity during extended culture. These findings identify NFC hydrogel as a biocompatible, non-animal scaffold that supports functional human nasal epithelium regeneration and may contribute to advanced tissue engineering strategies for craniofacial bone repair.

Adequate keratinized mucosa width (KMW) is important for maintaining peri-implant health, mechanical stability, and patient comfort. Although the free gingival graft (FGG) remains the most predictable method for increasing KMW, harvesting large grafts is often limited by palatal donor-site anatomy and associated morbidity. The slit free gingival graft (slit-FGG) is a straightforward modification that enables controlled width expansion without compromising structural continuity, thereby reducing donor tissue requirements. In this technique, a single full-thickness longitudinal incision is made in the harvested graft, creating two juxtaposed ribbons connected by intact lateral platforms. These ribbons can be displaced unidirectionally or bidirectionally to achieve the desired expansion and adapted over an apically positioned mucosa on a prepared periosteal bed. Four systemically healthy patients with insufficient KMW in large edentulous areas were treated using the slit-FGG as part of staged implant therapy. All patients reported minimal postoperative discomfort, and at 6 months the augmented sites demonstrated stable vestibular depth and maintained increases in KMW. Within the limitations of this report, the slit-FGG appears to represent a practical graft-efficient alternative for peri-implant soft-tissue phenotype modification when donor tissue is limited or extensive coverage is required.

Longitudinal Trends in Tissue-related Adverse Events after Corneal Transplantation.

There is a global shortage of donor tissue for corneal transplantation. Long-term stored ethanol-preserved corneoscleral tissue may help address this shortage, particularly in emergency cases of corneal perforation. This retrospective study analyzed tectonic keratoplasties for perforated corneal ulcers performed between January 2018 and December 2022. A total of 20 surgeries in 14 patients (6 female, 8 male) using ethanol-conserved corneoscleral tissue were included. Surgical, postoperative, and follow-up data were analyzed until December 2024, including graft storage duration, epithelialization, graft survival, complications, and best-corrected visual acuity. Outcomes were considered favorable if only planned surgery or no further surgery was required, and unfavorable if additional emergency intervention was necessary. The mean patient age was 83.5 (interquartile range 69.2-87.8) years (range 40.2-89.8). The cause of corneal perforation included immune-mediated corneal ulcers n = 8 (40%), neurotrophic corneal ulcers n = 7 (35%), herpetic corneal ulcerations n = 4 (20%), and fungal keratitis n = 1 (5%). The median graft size was 4.0 mm, with a median storage duration of 71.5 days (range 4-346). Graft survival resulted to 23.2 ± 17.4 months. A favorable outcome was achieved in 12 cases (60%). Epithelial closure was observed in all cases within 15 days. Best-corrected visual acuity improved from 1.7 ± 0.8 logMAR to 1.1 ± 0.7 logMAR. Ethanol-preserved corneoscleral tissue is safe and feasible for emergency tectonic keratoplasty. Its extended storage capacity may aid in the current global shortage of donor corneas.

Corneal fibrosis, clinically referred to as corneal scarring, disrupts the normal architecture and transparency of the cornea and remains a major cause of visual impairment worldwide. Although corneal transplantation can restore vision, its effectiveness is constrained by limited accessibility, donor tissue shortages, and the risk of allograft rejection. Treatments with human corneal stromal stem cells (hCSSCs) have demonstrated scarless healing in preclinical models of acute corneal injury. Here, we report that hCSSCs also modulated pre-existing corneal opacities. We established a reproducible in vivo model of chronic corneal opacity. Given that scar severity varies among corneas even after identical injuries, we developed a non-invasive, image-based method to quantify opacity volume longitudinally in individual corneas. Using this approach, we evaluated the scar-reducing potential of three hCSSC batches previously shown to inhibit acute scarring. Following cell treatment, the pre-existing opacity volumes gradually decreased. In vitro, hCSSCs exposed to pro-inflammatory stimulus exhibited increased metalloproteinase (MMP) activity relative to tissue inhibitor of metalloproteinase (TIMP), as indicated by an elevated MMP2/TIMP2 ratio. This shift may promote matrix remodeling and scar resolution. Overall, our findings provide proof-of-concept for hCSSC-based therapy as a strategy to reduce established corneal scarring and restore corneal transparency.

Research with BSL-4 viruses such as Ebola, Marburg, and Nipah presents significant challenges due to their high virulence and the stringent containment measures required. This study establishes human airway organoids as a robust model for investigating BSL-4 pathogens. In contrast to conventional cell lines, airway organoids enable investigation of virus-host interactions within a human tissue context, providing insights that are more directly translatable to human disease. We generated airway organoids from both clinical donor tissues and commercially available nasal epithelial cells and showed in comparative analyses with whole lung tissue that these organoids are comparable in terms of cell composition. Despite biological variations, airway organoids derived from different sources and donors exhibit a remarkably similar cellular make-up. We further demonstrated that organoids derived from nasal swabs can effectively replicate BSL-4 viruses. This establishes them as a standardized 3D model for broader research applications including infection kinetics, immune evasion, and tissue-specific tropism within a controlled environment. This platform provides a powerful tool for antiviral testing and studying virus-host interactions, thus helping bridge critical gaps in high containment virus research and advancing our understanding of these pathogens, bypassing some of the challenges of animal models.

Guttae are a hallmark of Fuchs endothelial corneal dystrophy (FECD) and the disease’s progression. A posterior fibrillar layer (PFL) that covers central guttae has been previously described, but its formation and progression remain unclear. This study aims to further investigate the characteristics of guttae and the PFL in FECD. In a well-characterized prospective FECD patient cohort, a total of 43 DMEK (Descemet membrane endothelial keratoplasty) specimens were immunostained for ZO1 or COL1, flat-mounted, and analyzed using differential interference contrast (DIC), autofluorescence (excited at 480 nm), and polarized light microscopy. Guttae and PFL were quantified and correlated with clinical data. Guttae were visualized by DIC and autofluorescence imaging and classified into two types with gradual transition: peripheral, knob-like guttae and central, flat guttae. Guttae with low autofluorescence often were covered by corneal endothelial cells (CEnC). Central guttae were found to be covered by a PFL that contained COL1 and was visualized using polarized light microscopy. The PFL displayed a fibrous structure that blurred guttae in DIC illumination. Its presence correlated with clinical parameters, such as anterior scatter and post-operative corneal edema resolution providing insight into the relation of PFL and FECD severity. The combination of DIC, autofluorescence, and polarized light microscopy provides a robust method for investigating guttae and the PFL. This could facilitate preoperative assessment of corneal donor tissue and enhance postoperative clinical diagnostics by detailed detection of guttae and PFL in patients.