Exploiting urine-derived induced pluripotent stem cells for advancing precision medicine in cell therapy, disease modeling, and drug testing.

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

Bioengineering autologous cartilage grafts for functional posterior lamellar eyelid reconstruction: A preliminary study in rabbits.

The reconstruction of posterior lamellar eyelid defects remains a significant challenge in clinical practice due to anatomical complexity, specialized function, and aesthetic concerns. The ideal substitute for the posterior lamellar should replicate the native tarsoconjunctival tissue, providing both mechanical support for the eyelids and a smooth surface for the globe after implantation. In this study, we present an innovative approach utilizing tissue-engineered cartilage (TEC) grafts generated from rabbit auricular chondrocytes and a commercialized type I collagen sponge to reconstruct critical-sized posterior lamellar defects in rabbits. The TEC grafts demonstrated remarkable mechanical strength and maintained a stable cartilaginous phenotype both in vitro and at 6 months post-implantation in immunodeficient mice. When employed as autografts to reconstruct tarsal plate defects in rabbits' upper eyelids, these TEC grafts successfully restored normal eyelid morphology, facilitated smooth eyelid movement, and preserved the histological structure of the conjunctival epithelium. When applied in bilayered tarsoconjunctival defect reconstruction, these TEC grafts not only maintained the normal contour of the upper eyelid but also supported conjunctival epithelial cell migration and growth from the defect margin towards the centre. These findings highlight that auricular chondrocyte-based TEC grafts hold great promise as potential candidates for clinical posterior lamellar reconstruction. STATEMENT OF SIGNIFICANCE: The complex structure and function of the posterior lamellar eyelid continue to be significant challenges for clinical reconstructive surgeries. In this study, we utilized autologous auricular chondrocyte-based TEC grafts for posterior lamellar eyelid reconstruction in a preclinical rabbit model. The TEC grafts exhibited native cartilaginous histomorphology and comparable mechanical strength to those of the native human tarsal plate. In rabbit models with either tarsal plate defects alone or bilayered tarsoconjunctival defects, TEC grafts successfully restored the normal eyelid contour and movement, as well as supported preservation and growth of conjunctival epithelium. This is the first study to demonstrate autologous TEC grafts can be employed for repairing tarsal plate defects, thereby offering an alternative therapeutic approach for treating posterior lamellar defects in clinic settings.

Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy.

Diabetes presents a pressing healthcare crisis, necessitating innovative solutions. Organoid technologies have rapidly advanced, leading to the emergence of bioengineering islet organoids as an unlimited source of insulin-producing cells for treating insulin-dependent diabetes. This advancement surpasses the need for cadaveric islet transplantation. However, clinical translation of this approach faces two major limitations: immature endocrine function and the absence of a perfusable vasculature compared to primary human islets. In this review, we summarize the latest developments in bioengineering functional islet organoids in vitro and promoting vascularization of organoid grafts before and after transplantation. We highlight the crucial roles of the vasculature in ensuring long-term survival, maturation, and functionality of islet organoids. Additionally, we discuss key considerations that must be addressed before clinical translation of islet organoid-based therapy, including functional immaturity, undesired heterogeneity, and potential tumorigenic risks.

Biomaterials and tissue engineering strategies for posterior lamellar eyelid reconstruction: Replacement or regeneration?

Reconstruction of posterior lamellar eyelids remains challenging due to their delicate structure, highly specialized function, and cosmetic concerns. Current clinically available techniques for posterior lamellar reconstruction mainly focus on reconstructing the contour of the eyelids. However, the posterior lamella not only provides structural support for the eyelid but also offers a smooth mucosal surface to facilitate globe movement and secrete lipids to maintain ocular surface homeostasis. Bioengineered posterior lamellar substitutes developed via acellular or cellular approaches have shown promise as alternatives to current therapies and encouraging outcomes in animal studies and clinical conditions. Here, we provide a brief reference on the current application of autografts, biomaterials, and tissue-engineered substitutes for posterior lamellar eyelid reconstruction. We also shed light on future challenges and directions for eyelid regeneration strategies and offer perspectives on transitioning replacement strategies to regeneration strategies for eyelid reconstruction in the future.

Urine-Derived Stem Cells for Epithelial Tissues Reconstruction and Wound Healing.

Epithelial tissue injury can occur on any surface site of the body, particularly in the skin or urethral mucosa tissue, due to trauma, infection, inflammation, and toxic compounds. Both internal and external body epithelial tissue injuries can significantly affect patients' quality of life, increase healthcare spending, and increase the global economic burden. Transplantation of epithelial tissue grafts is an effective treatment strategy in clinical settings. Autologous bio-engineered epithelia are common clinical skin substitutes that have the specific advantages of avoiding tissue rejection, obviating ethical concerns, reducing the risk of infection, and decreasing scarring compared to donor grafts. However, epithelial cells are often obtained from the individual's skin and mucosa through invasive methods, which cause further injury or damage. Urine-derived stem cells (USC) of kidney origin, obtained via non-invasive acquisition, possess high stemness properties, self-renewal ability, trophic effects, multipotent differentiation potential, and immunomodulatory ability. These cells show versatile potential for tissue regeneration, with extensive evidence supporting their use in the repair of epidermal and urothelial injuries. We discuss the collection, isolation, culture, characterization, and differentiation of USC. We also discuss the use of USC for cellular therapies as well as the administration of USC-derived paracrine factors for epidermal and urothelial tissue repair. Specifically, we will discuss 3D constructions involving multiple types of USC-loaded hydrogels and USC-seeded scaffolds for use in cosmetic production testing, drug development, and disease modeling. In conclusion, urine-derived stem cells are a readily accessible autologous stem cell source well-suited for developing personalized medical treatments in epithelial tissue regeneration and drug testing.

Surgical Strategies for Eyelid Defect Reconstruction: A Review on Principles and Techniques.

Reconstruction of eyelid defects, especially the posterior lamella, remains challenging because of its anatomical complexity, functional considerations, and aesthetic concerns. The goals of eyelid reconstruction include restoring eyelid structure and function and achieving an aesthetically acceptable appearance. An in-depth understanding of the complex eyelid anatomy and several reconstructive principles are mandatory to achieve these goals. Currently, there are multiple surgical treatment options for eyelid reconstruction, including different flaps, grafts, and combinations of them. This comprehensive review outlines the principles of reconstruction and discusses the indications, advantages, and disadvantages of currently available surgical techniques. We also propose our clinical thinking for solving specific clinical questions in eyelid reconstruction and offer perspectives on new potential methodologies in the future.

Management of Cutaneous Angiosarcoma: an Update Review.

OPINION STATEMENT: Cutaneous angiosarcoma is a rare and invasive malignant tumor. For localized cAS patients, wide-margin excision was recommended. Due to the latent local invasion characteristic of cAS, we suggest preoperative and postoperative radiotherapy to nearly all patients. Recently, there is growing interest in using neoadjuvant chemotherapy and/or radiotherapy as part of a combination therapy regimen, which may allow some patients to undergo potentially less disabling surgery. For metastatic cAS patients with unresectable tumors and who refuse surgery, radical radiotherapy or chemoradiotherapy may be an option. Paclitaxel was recognized as the first-line treatment. For tumors resistant to taxanes, emerging medications such as targeted agents and immunotherapy are also under investigation.

Analysis for effects of lanthanum (III) on the aboveground modules and respiration of soybean populations.

The accumulation of rare earth elements (REEs) in the environment has become an environmental safety issue that cannot be ignored. However, previous studies on the environmental risks of REEs have mostly been performed at the individual level. In this work, to explore the effects of REE pollution at the population level, the effects of lanthanum (III) [La(III)] on the aboveground modules of soybean (Glycine max L) populations at different planting densities were investigated by simulating La(III) pollution, and the underlying mechanism was revealed on the physiological and biochemical levels of respiration. The results showed that the addition of 0.4 and 1.2 mM La(III) decreased the aboveground module growth parameters of the soybean populations, and this effect was more evident in the 1.2 mM La(III) treatment. At a certain dose of La(III), the effects of La(III) on the aboveground module growth parameters decreased with increasing plant densities. In addition, the effects of La(III) on the aboveground module growth parameters of soybean plants at different planting densities were related to plant respiration, in particular, to changes in the activities of respiratory key enzymes. The results indicated that the inhibitory effects of La(III) depended on the dose and on the planting density. This finding could provide a novel perspective and a basis for the objective assessment of potential environmental risks of REEs. ONE SENTENCE SUMMARY: La(III) pollution effects on the aboveground modules of soybean populations are related to the changes of the population respiration and the respiratory key enzymes; moreover, these effects are restricted by the population density.