Cell Sheets Research Articles

Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation.

Electroporation is a promising nonthermal ablation method for cardiac arrhythmia treatment. Although initial clinical studies found electroporation pulsed-field ablation (PFA) both safe and efficacious, there are significant knowledge gaps concerning the mechanistic nature and electrophysiological consequences of cardiomyocyte electroporation, contributed by the paucity of suitable human in vitro models. Here, we aimed to establish and characterize a functional in vitro model based on human-induced pluripotent stem cells (hiPSCs)-derived cardiac tissue, and to study the fundamentals of cardiac PFA. hiPSC-derived cardiomyocytes were seeded as circular cell sheets and subjected to different PFA protocols. Detailed optical mapping, cellular, and molecular characterizations were performed to study PFA mechanisms and electrophysiological outcomes. PFA generated electrically silenced lesions within the hiPSC-derived cardiac circular cell sheets, resulting in areas of conduction block. Both reversible and irreversible electroporation components were identified. Significant electroporation reversibility was documented within 5 to 15-minutes post-PFA. Irreversibly electroporated regions persisted at 24-hours post-PFA. Per single pulse, high-frequency PFA was less efficacious than standard (monophasic) PFA, whereas increasing pulse-number augmented lesion size and diminished reversible electroporation. PFA augmentation could also be achieved by increasing extracellular Ca2+ levels. Flow-cytometry experiments revealed that regulated cell death played an important role following PFA. Assessing for PFA antiarrhythmic properties, sustainable lines of conduction block could be generated using PFA, which could either terminate or isolate arrhythmic activity in the hiPSC-derived cardiac circular cell sheets. Cardiac electroporation may be studied using hiPSC-derived cardiac tissue, providing novel insights into PFA temporal and electrophysiological characteristics, facilitating electroporation protocol optimization, screening for potential PFA-sensitizers, and investigating the mechanistic nature of PFA antiarrhythmic properties.

New Perspectives in Stem Cell Transplantation and Associated Therapies to Treat Retinal Diseases: From Gene Editing to 3D Bioprinting.

Inherited and non-inherited retinopathies can affect distinct cell types, leading to progressive cell death and visual loss. In the last years, new approaches have indicated exciting opportunities to treat retinopathies. Cell therapy in retinitis pigmentosa, age-related macular disease, and glaucoma have yielded encouraging results in rodents and humans. The first two diseases mainly impact the photoreceptors and the retinal pigmented epithelium, while glaucoma primarily affects the ganglion cell layer. Induced pluripotent stem cells and multipotent stem cells can be differentiated in vitro to obtain specific cell types for use in transplant as well as to assess the impact of candidate molecules aimed at treating retinal degeneration. Moreover, stem cell therapy is presented in combination with newly developed methods, such as gene editing, Müller cells dedifferentiation, sheet & drug delivery, virus-like particles, optogenetics, and 3D bioprinting. This review describes the recent advances in this field, by presenting an updated panel based on cell transplants and related therapies to treat retinopathies.

Extranodal Marginal Zone Lymphoma of Mucosa Associated Lymphoid Tissue (MALT LYMPHOMA) With Extensive Plasma Cell Differentiation and Localized Amyloid Deposition.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a mature and clinically indolent B cell lymphoma composed of heterogeneous cell population. Plasma cell differentiation is commonly seen in MALT lymphomas. However, plasmacytic differentiation along with localized amyloid deposition in the lungs is an extremely rare. We encountered a unique case of Extranodal MALT lymphoma with extensive plasmacytic differentiation and amyloid deposition. A 78-year-old female with past history of Gastric MALT lymphoma, status post chemotherapy presented in outpatient clinic. PET scan revealed an incidental 9 mm nodule in left lung, and subsequently underwent biopsy. Histology showed sheets of heterogeneous neoplastic cells including small lymphocytes, monocytoid cells, and abundant number of plasma cells (Fig A) in the background of hyalinization (Fig B). Immunohistochemical (IHC) reveals lymphoma cells are positive for CD20 (Fig C) and CD43, and plasma cells showed lambda restriction (Fig D). Furthermore, Congo Red stain of eosinophilic background showed positive birefringence upon polarization, consistent with Amyloid. Great caution is required in differentiating these cases from lymphoplasmacytic lymphoma as the histologic and IHC features can significantly overlap, and studies have also suggested that plasmacytic differentiation in these cases represent precursor neoplasm of plasma cells. Amyloid depositions in MALT lymphomas are rare and organ confined but can lead to local complications and cause considerable morbidity. Therefore, it is necessary to be aware of the association between MALT lymphoma with extensive plasma cell differentiation and amyloid deposition, as close clinical follow up is recommended.

Regeneration of the Retina Using Pluripotent Stem Cells: A Comprehensive Review.

Retinitis pigmentosa and age-related macular degeneration are the most frequent causes of irreversible visual impairment in the world. Existing therapeutic methods could be more effective, underscoring the necessity of new treatments. Reconstructing the retinal photoreceptors through the transplantation of human pluripotent stem cells, representing an attractive approach for restoring vision, has gained momentum. This paper gives an exhaustive account of what has been known in this field, the discoveries made, and the recent progress. This review paper outlines the retina's organisation, cell types, the pathophysiology of retinal injury/degeneration, and the reasoning behind using pluripotent stem cells in retinal regeneration. This article investigates differentiation strategies, molecular components that dictate cell type specification, and the recreation of retinal development in vitro, genetically engineering and manipulating epigenetic marks using various techniques for driving specific cell fates and improving therapy efficacy. Subretinal injection methods, cell encapsulation techniques, scaffold-based approaches, cell sheet transplantation, and their impact on integrating implanted cells into a functional retina are thoroughly reviewed. Using bioengineering approaches, biomaterials and growth factors form a favourable micro-ambience for grafted cells. Issues around safety and efficacy (tumorigenicity, immunological rejection, and long-term integration/functionality) are explored. Moreover,the paper emphasises the significance of rigorous characterisation, immunomodulatory strategies, and clinical and pre-clinical studies to ensure the safety and effectiveness of retinal regeneration therapy. Future perspectives and challenges are presented, looking at fine-tuning differentiation strategies, improving functional integration and regulatory aspects, and using co-therapy and supportive treatments.

Tailoring cell sheets for biomedical applications

AbstractCell sheet technology has emerged as a novel scaffold‐free approach for cell‐based therapies in regenerative medicine. Techniques for harvesting cell sheets are essential to preserve the integrity of living cell sheets. This review provides an overview of fundamental technologies to fabricate cell sheets and recent advances in cell sheet‐based tissue engineering. In addition to the commonly used temperature‐responsive systems, we introduce alternative approaches, such as ROS‐induced, magnetic‐controlled, and light‐induced cell sheet technologies. Moreover, we discuss the modification of the cell sheet to improve its function, including stacking, genetic modification, and vascularization. With the significant advances in cell sheet technology, cell sheets have been widely applied in various tissues and organs, including but not limited to the lung, cornea, cartilage, periodontium, heart, and liver. This review further describes both the preclinical and clinical applications of cell sheets. We believe that the progress in cell sheet technology would further propel its biomedical applications.

Classification Evaluation Method Considering the Effect of Specific Gravity Sorting in Air Classification—Case Study of Solar Panel Cell Sheets Classification—

Classification Evaluation Method Considering the Effect of Specific Gravity Sorting in Air Classification—Case Study of Solar Panel Cell Sheets Classification—

Production of alginate macrocapsule device for long-term normoglycaemia in the treatment of type 1 diabetes mellitus with pancreatic cell sheet engineering

Type 1 diabetes-mellitus (T1DM) is characterized by damage of beta cells in pancreatic islets. Cell-sheet engineering, one of the newest therapeutic approaches, has also been used to create functional islet systems by creating islet/beta cell-sheets and transferring these systems to areas that require minimally invasive intervention, such as extrahepatic areas. Since islets, beta cells, and pancreas transplants are allogeneic, immune problems such as tissue rejection occur after treatment, and patients become insulin dependent again. In this study, we aimed to design the most suitable cell-sheet treatment method and macrocapsule-device that could provide long-term normoglycemia in rats. Firstly, mesenchymal stem cells (MSCs) and beta cells were co-cultured in a temperature-responsive culture dish to obtain a cell-sheet and then the cell-sheets macroencapsulated using different concentrations of alginate. The mechanical properties and pore sizes of the macrocapsule-device were characterized. The viability and activity of cell-sheets in the macrocapsule were evaluated in vitro and in vivo. Fasting blood glucose levels, body weight, and serum insulin & C-peptide levels were evaluated after transplantation in diabetic-rats. After the transplantation, the blood glucose level at 225 mg dl–1 on the 10th day dropped to 168 mg dl–1 on the 15th day, and remained at the normoglycemic level for 210 days. In this study, an alginate macrocapsule-device was successfully developed to protect cell-sheets from immune attacks after transplantation. The results of our study provide the basis for future animal and human studies in which this method can be used to provide long-term cellular therapy in T1DM patients.

Regulatory mechanisms and regeneration strategies of the soft–hard tissue interface in the human periodontium

AbstractThe soft‐hard tissue interface of the human periodontium is responsible for periodontal homeostasis and is essential for normal oral activities. This soft‐hard tissue interface is formed by the direct insertion of fibrous ligaments into the bone tissue. It differs from the unique four‐layer structure of the fibrocartilage interface. This interface is formed by a combination of physical, chemical, and biological factors. The physiological functions of this interface are regulated by different signaling pathways. The unique structure of this soft‐hard tissue interface has inspired scientists to construct biomimetic gradient structures. These biomimetic systems include nanofiber scaffolds, cell sheets, and hydrogels. Exploring methods to repair this soft‐hard tissue interface can help solve clinically unresolved problems. The present review examines the structure of the soft‐hard tissue interface of the periodontium and the factors that influence the development of this interface. Relevant regulatory pathways and biomimetic reconstruction methods are also presented to provide ideas for future research on interfacial tissue engineering.

Comprehensive Tools of Alkaloid/Volatile Compounds-Metabolomics and DNA Profiles: Bioassay-Role-Guided Differentiation Process of Six Annona sp. Grown in Egypt as Anticancer Therapy.

Trees of the Annona species that grow in the tropics and subtropics contain compounds that are highly valuable for pharmacological research and medication development and have anticancer, antioxidant, and migratory properties. Metabolomics was used to functionally characterize natural products and to distinguish differences between varieties. Natural products are therefore bioactive-marked and highly respected in the field of drug innovation. Our study aimed to evaluate the interrelationships among six Annona species. By utilizing six Start Codon Targeted (SCoT) and six Inter Simple Sequence Repeat (ISSR) primers for DNA fingerprinting, we discovered polymorphism percentages of 45.16 and 35.29%, respectively. The comparison of the profiles of 78 distinct volatile oil compounds in six Annona species was accomplished through the utilization of GC-MS-based plant metabolomics. Additionally, the differentiation process of 74 characterized alkaloid compound metabolomics was conducted through a structural analysis using HPLC-ESI-MSn and UPLC-HESI-MS/MS, and antiproliferative activities were assessed on five in vitro cell lines. High-throughput, low-sensitivity LC/MS-based metabolomics has facilitated comprehensive examinations of alterations in secondary metabolites through the utilization of bioassay-guided differentiation processes. This has been accomplished by employing twenty-four extracts derived from six distinct Annona species, which were subjected to in vitro evaluation. The primary objective of this evaluation was to investigate the IC50 profile as well as the antioxidant and migration activities. It should be noted, however, that these investigations were exclusively conducted utilizing the most potent extracts. These extracts were thoroughly examined on both the HepG2 and Caco cell lines to elucidate their potential anticancer effects. In vitro tests on cell cultures showed a significant concentration cytotoxic effect on all cell lines (HepG2, HCT, Caco, Mcf-7, and T47D) treated with six essential oil samples at the exposure time (48 h). Therefore, they showed remarkable antioxidant activity with simultaneous cytotoxic effects. In total, 50% and 80% of the A. muricata extract, the extract with the highest migratory activity, demonstrated a dose-dependent inhibition of migration. It was strong on highly metastatic Caco cells 48 h after treatment and scraping the Caco cell sheet, with the best reduction in the migration of HepG2 cells caused by the 50% A. reticulata extract. Also, the samples showing a significant IC50 value showed a significant effect in stopping metastasis and invasion of various cancer cell lines, making them an interesting topic for further research.

Effects of a second iron-dextran injection administered to piglets during lactation on differential gene expression in liver and duodenum at weaning.

Six female littermate piglets were used in an experiment to evaluate the mRNA expression in tissues from piglets given one or two 1mL injections of iron dextran (200mg Fe/mL). All piglets in the litter were administered the first 1mL injection < 24h after birth. On day 7, piglets were paired by weight (mean body weight = 1.72 ± 0.13kg) and one piglet from each pair was randomly selected as control (CON) and the other received a second injection (+Fe). At weaning on day 22, each piglet was anesthetized, and samples of liver and duodenum were taken from the anesthetized piglets and preserved until mRNA extraction. differential gene expression data were analyzed with a fold change cutoff (FC) of |1.2| P < 0.05. Pathway analysis was conducted with Z-score cutoff of P < 0.05. In the duodenum 435 genes were significantly changed with a FC ≥ |1.2| P < 0.05. In the duodenum, Claudin 1 and Claudin 2 were inversely affected by + Fe. Claudin 1 (CLDN1) plays a key role in cell-to-cell adhesion in the epithelial cell sheets and was upregulated (FC = 4.48, P = 0.0423). Claudin 2 (CLDN2) is expressed in cation leaky epithelia, especially during disease or inflammation and was downregulated (FC = -1.41, P = 0.0097). In the liver, 362 genes were expressed with a FC ≥ |1.2| P < 0.05. The gene most affected by a second dose of 200mg Fe was hepcidin antimicrobial peptide (HAMP) with a FC of 40.8. HAMP is a liver-produced hormone that is the main circulating regulator of Fe absorption and distribution across tissues. It also controls the major flows of Fe into plasma by promoting endocytosis and degradation of ferroportin (SLC4A1). This leads to the retention of Fe in Fe-exporting cells and decreased flow of Fe into plasma. Gene expression related to metabolic pathway changes in the duodenum and liver provides evidence for the improved feed conversion and growth rates in piglets given two iron injections preweaning with contemporary pigs in a companion study. In the duodenum, there is a downregulation of gene clusters associated with gluconeogenesis (P < 0.05). Concurrently, there was a decrease in the mRNA expression of genes for enzymes required for urea production in the liver (P < 0.05). These observations suggest that there may be less need for gluconeogenesis, and possibly less urea production from deaminated amino acids. The genomic and pathway analyses provided empirical evidence linking gene expression with phenotypic observations of piglet health and growth improvements.

Fibronectin Connecting Cell Sheet Based on Click Chemistry for Wound Repair.

As a living repair material, cell sheet exhibits significant potential in wound repair. Nonetheless, wound healing is a complicated and protracted process that necessitates specific repair functions at each stage, including hemostasis and antibacterial activity. In this work, on the basis of harvesting the cell sheet via a photothermal response strategy, a fibronectin attached cell sheet (FACS) is prepared to enhance its wound repair capability. For this purpose, the azide group (N3 ) is initially tagged onto the cell surface through metabolic glycoengineering of unnatural sugars, and then the conjugate (DBCO-fibronectin) comprises of the dibenzocyclooctyne (DBCO) and fibronectin with multiple wound repair functions is linked to N3 using click chemistry. Biological evaluations following this demonstrates that the FACS preparation exhibits excellent biocompatibility, and the fibronectin modification enhances the capacity for cell proliferation and migration. Moreover, in vivo wound healing experiment confirms the reparative efficacy of FACS. It not only has a wound closure rate 1.46 times that of a conventional cell sheet but also reduces inflammatory cell infiltration, promotes hair follicle and blood vessel regeneration, and encourages collagen deposition. This strategy holds enormous clinical potential and paves the way for advanced functional modifications of cell sheets.

IMMUNOMODULATORY POTENTIAL OF MAGNETICALLY ASSISTED CELL SHEET UNDER HYPOXIC ENVIRONMENTS UPON MAGNETIC STIMULATION

Common tendon injuries impair healing, leading to debilitation and an increased re-rupture risk. The impact of oxygen-sensing pathways on repair mechanisms, vital in regulating inflammation and fibrosis, remains unclear despite their relevance in tendon pathologies. Recent studies show that pulsed electromagnetic field (PEMF) reduce inflammation in human tendon cells (hTDCs) and in hypoxia-induced inflammation. We investigated the hypoxia's impact (1% and 2% oxygen tension) using magnetic cell sheet constructs (IL-1β-magCSs) primed with IL-1β. IL-1β-magCSs were exposed to low OT (1h, 4h,6h) in a hypoxic chamber. To confirm the role of PEMF (5Hz, 4mT, 50% duty cycle) on hypoxia modulation, IL-1β-magCSs, previously exposed to OT, were 1h-stimulated with PEMF. Our results show a significant increase in HIF- 1a and HIF-2a expression on IL-1β-magCSs after exposure to 2%-OT at all time points, compared to 1%- OT and normoxia. TNFa, IL-6, and IL-8 expression increased after 6 hours of 1%-OT exposure. PEMF stimulation of hypoxic IL-1β-magCSs led to decreased pro-inflammatory genes and increased anti-inflammatory (IL-4,IL-10) expression compared to unstimulated magCSs. IFN-g, TNF-α, and IL-6 release increased after 6 hours, regardless of %-OT, while IL-10 levels tended to rise after PEMF stimulation at 2%-OT. Also, NFkB expression was increased on IL-1β-magCSs exposed to 4 h and 6 h of 2%-OT, suggesting a link between NFkB and the production of pro-inflammatory factors. Moreover, PEMF stimulation showed a significantly decreased NFkB level in IL-1β-magCSs.Overall, low OT enhances expression of hypoxia-associated genes and inflammatory markers in IL-1β-magCSs with the involvement of NFkB. PEMF modulates the response of magCSs, previously conditioned to hypoxia and to inflammatory triggers, favouring expression of anti-inflammatory genes and proteins, supporting PEMF impact in pro-regenerative tendon strategies.Acknowledgements: ERC CoG MagTendon(No.772817), FCT under the Scientific Employment Stimulus-2020.01157.CEECIND. Thanks to Hospital da Prelada for providing tendon tissue samples (Portugal), and TERMRES Hub (Norte-01-0145-FEDER-022190).

Cell sheet produced from periodontal ligament stem cells activated by PAR1 improves osteogenic differentiation.

Periodontal regeneration is a challenge, and tissue engineering based on periodontal ligament stem cells (PDLSCs) has been shown to be a promising alternative to this process. However, the need for scaffolds has limited the therapeutic use of PDLSCs. In this context, scaffold-free tissue engineering using the cell sheet (CS) technique has been developed as an alternative approach to improve tissue regeneration. Previously, we showed that Protease-activated receptor-1 (PAR1) can regulate PDLSCs. Herein, we evaluate whether PAR1 influences osteogenesis in CSs produced from PDLSCs, without the use of scaffolds. PDLSCs were isolated and immunophenotyped. Then, CSs were obtained by supplementing the culture medium with ascorbic acid (50 µg/mL), and PAR1 was activated through its agonist peptide (100 nM). Scaffold-free 3D CSs were successfully produced from PDLSCs, and they showed higher proliferation potential than isolated PDLSCs. Also, PAR1 activation decreased senescence and improved osteogenic differentiation of CSs by increasing mineralized nodule deposition and alkaline phosphatase concentration; PAR1 also modulated osteogenic markers at the gene and protein levels. We further demonstrated that this effect was regulated by Wnt, TGF-βI, MEK, p38 MAPK, and FGF/VEGF signaling pathways in PDLSCs (p < 0.05%). Overall, PAR1 activation increased osteogenic activity in CSs, emerging as a promising scaffold-free therapeutic approach for periodontal regeneration.

Transplantation of Stem Cell Spheroid-Laden 3-Dimensional Patches with Bioadhesives for the Treatment of Myocardial Infarction.

Myocardial infarction (MI) is treated with stem cell transplantation using various biomaterials and methods, such as stem cell/spheroid injections, cell sheets, and cardiac patches. However, current treatment methods have some limitations, including low stem cell engraftment and poor therapeutic effects. Furthermore, these methods cause secondary damage to heart due to injection and suturing to immobilize them in the heart, inducing side effects. In this study, we developed stem cell spheroid-laden 3-dimensional (3D) patches (S_3DP) with biosealant to treat MI. This 3D patch has dual modules, such as open pockets to directly deliver the spheroids with their paracrine effects and closed pockets to improve the engraft rate by protecting the spheroid from harsh microenvironments. The spheroids formed within S_3DP showed increased viability and expression of angiogenic factors compared to 2-dimensional cultured cells. We also fabricated gelatin-based tissue adhesive biosealants via a thiol-ene reaction and disulfide bond formation. This biosealant showed stronger tissue adhesiveness than commercial fibrin glue. Furthermore, we successfully applied S_3DP using a biosealant in a rat MI model without suturing invivo, thereby improving cardiac function and reducing heart fibrosis. In summary, S_3DP and biosealant have excellent potential as advanced stem cell therapies with a sutureless approach to MI treatment.

Seepage and Swelling-Neuroendocrine Tumour Testis

Neuroendocrine tumour of testis configures a well differentiated neuroendocrine tumour or a low grade, epithelial neoplasm demonstrating neuroendocrine differentiation. Testicular neuroendocrine tumour may concur with pre-pubertal teratoma or exceptionally articulate as a post-pubertal subtype. Tumour cells manifest with a near diploid genotype. Tumour cells appear devoid of is chromosome 12p or numerical aberrations confined to X chromosome. Cytological examination exhibits isolated singular cells or sheets of neoplastic cells permeated with granular cytoplasm, uniform, spherical nuclei and evenly distributed, fine nuclear chromatin. Morphologically, tumefaction exhibits cellular nests, glands with intra-luminal mucin, solid sheets, insular, acinar or trabecular pattern of tumour evolution. Monomorphic neoplastic cells are pervaded with abundant, granular, eosinophilic cytoplasm, regular spherical nuclei and fine or salt and pepper nuclear chromatin, encompassed within a delicate, fibrous or hyalinised stroma.

Ewing’s Sarcoma of the Mandible with Extensive Bony Metastasis in a Young Male: A Case Report

Ewing’s Sarcoma Family of Tumours (ESFTs) comprises locally aggressive, undifferentiated small round blue-cell tumours of neuroectodermal origin, predominantly seen in adolescents. These tumours arise from non random chromosomal translocations involving the Ewing’s Sarcoma (EWS) gene. ESFTs in the mandible are uncommon. A 14-year-old male patient presented with a painless swelling in the right jaw. Plain radiographs, ultrasonography, contrast-enhanced Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) revealed a large, partially well-defined, highly vascular soft tissue mass in the right mandibular region. It measured approximately 80×82×75 mm (anteroposterior x transverse x craniocaudal), with both solid and cystic components. The mass was destroying the underlying right temporomandibular joint, head, ramus and posterior body of the right hemimandible, including extensive sunray-type bony spiculations. There were multiple lytic lesions in the skull and facial bones, as well as, altered marrow signal intensity in the calvarium, bilateral humeri and clavicles, and cervical and thoracic vertebrae, indicating a locally aggressive tumour with extensive metastasis into the bones and marrow. The diagnosis was confirmed by histopathology, which showed fibrocollagenous tissue infiltrated by sheets of small round cells with scanty eosinophilic cytoplasm and prominent nuclei. Management typically involves a combination of chemotherapy, radiation and surgery. However, metastatic Ewing’s Sarcoma has a poor prognosis.

In Vitro Culture of White Adipose Tissue.

White adipose tissue (WAT) plays a crucial endocrine organ that regulates blood glucose and lipid levels, satiety, and inflammation. Before the described technique, primary white adipocytes could not be stably cultured in vitro. The lack of a reliable primary culture model impeded research in WAT metabolism and drug development. We have developed a novel technique for WAT primary culture called "sandwiched white adipose tissue" (SWAT). SWAT overcomes the natural buoyancy of adipocytes by sandwiching minced WAT between sheets of adipose-derived stromal cells. The resulting constructs are viable for at least 8weeks in culture. SWAT maintains the intact extracellular matrix, cell-to-cell contacts, and physical pressures of in vivo WAT conditions; additionally, SWAT maintains a robust transcriptional profile, sensitivity to exogenous chemical signaling, and whole tissue function. SWAT represents a simple, reproducible, and effective method of primary adipose culture. Potentially, it is a broadly applicable platform for research in WAT physiology, pathophysiology, metabolism, and pharmaceutical development.

Advances in cartilage tissue regeneration: a review of stem cell therapies, tissue engineering, biomaterials, and clinical trials.

Cartilage tissue, characterized by its limited regenerative capacity, presents significant challenges in clinical therapy. Recent advancements in cartilage regeneration have focused on integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to overcome existing limitations. Stem cells, particularly Mesenchymal Stem Cells (MSCs) and induced pluripotent stem cells (iPSCs), hold promise for cartilage repair due to their ability to differentiate into chondrocytes, the key cells responsible for cartilage formation. Tissue engineering approaches, including 3D models, organ-on-a-chip systems, and organoids, offer innovative methods to mimic natural tissue microenvironments and evaluate potential treatments. MSC-based techniques, such as cell sheet tissue engineering, address challenges associated with traditional therapies, including cell availability and culture difficulties. Furthermore, advancements in 3D bioprinting enable the fabrication of complex tissue structures, while organ-on-a-chip systems provide microfluidic platforms for disease modeling and physiological mimicry. Organoids serve as simplified models of organs, capturing some complexity and enabling the monitoring of pathophysiological aspects of cartilage diseases. This comprehensive review underscores the transformative potential of integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to improve cartilage regeneration and pave the way for more effective clinical treatments.

Cell Sheet Engineering in Periodontology: A Review

Cell sheet engineering has developed its own place for the regeneration of tissues. It focuses on phenomena occurring at the cellular level, whereas regenerative medicine and tissue engineering aim to create or stimulate new tissue for the treatment of disease. In medicine and dentistry, tissue engineering, cell-based therapies, and regenerative medicine have been progressing rapidly for regeneration procedures. It has emerged as a promising strategy for scaffold-free cell-based regenerative medicine therapy by means of transplantable single or multi-layered cell-dense sheets to achieve tissue repair and regeneration. Cell sheet engineering could be one of the procedures for regeneration of periodontal tissues, which can yield better results. In this review, the authors will highlight the principal techniques of cell sheet engineering and its application in tissue regeneration in periodontal therapy.

Diagnosis of Infarcted Breast Lesions on FNAC, a Blustering Fool: Short Case Series.

Fine-needle aspiration cytology (FNAC) is often used as a screening tool. Cytopathologist should be aware of various mimickers of the malignancy. One of these is infarction of benign breast lesions. Careful examination of cytomorphological features will avoid the misdiagnosis of malignancy in such cases. Six cases were diagnosed as benign breast lesion for 4 years and 5 months in our newly established tertiary referral center. Histopathology follow-up was available in one case. Of six cases, three cases (50%) were reported as fibroadenoma with infarction, two cases (33%) as benign breast lesion with infarction favor fibroadenoma, and one as breast lesion with infarction favor phyllodes tumor in view of recurrence. Most were in the second or third decade of their life. All cases showed dyscohesive cells with pyknotic nuclei. Monolayered sheets of necrotic cells were seen in the four cases (66%). Viable cells were seen in four cases. FNAC provides a rapid and accurate diagnosis of benign breast lesions with infarction in the hands of experienced pathologists who can help in better patient care. Small-sized uniform pyknotic nuclei of dyscohesive cells and regular nuclear membranes help to differentiate them from inflammatory and malignant lesions.