Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair.

Exosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further research is necessary to optimize exosome therapy, not only in the areas of exosome isolation, characterization, and engineering, but also in determining the optimal dose, timing, administration, and frequency of exosome therapy. Thus, optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer, ischemia, or inflammation. This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.

Therapeutic Benefits of Stem Cells and Exosomes for Sulfur-Mustard-Induced Tissue Damage.

Sulfur mustard (SM) is a highly toxic chemical agent that causes severe tissue damage, particularly to the eyes, lungs, and skin. Despite advances in treatment, there is a need for more effective therapies for SM-induced tissue injury. Stem cell and exosome therapies are emerging as promising approaches for tissue repair and regeneration. Stem cells can differentiate into multiple cell types and promote tissue regeneration, while exosomes are small vesicles that can deliver therapeutic cargo to target cells. Several preclinical studies demonstrated the potential of stem cell, exosome, or combination therapy for various tissue injury, showing improvements in tissue repairing, inflammation, and fibrosis. However, there are also challenges associated with these therapies, such as the requirement for standardized methods for exosome isolation and characterization, the long-term safety and efficacy and reduced SM-induced tissue injury of these therapies. Stem cell or exosome therapy was used for SM-induced eye and lung injury. Despite the limited data on the use for SM-induced skin injury, this therapy is a promising area of research and may offer new treatment options in the future. In this review, we focused on optimizing these therapies, evaluating their safety and efficacy, and comparing their efficacy to other emerging therapeutic approaches potentially for SM-induced tissue injury in the eye, lung, and skin.

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.

Cultivation and characterization of limbal epithelial stem cells on contact lenses with a feeder layer: toward the treatment of limbal stem cell deficiency.

PURPOSE: Limbal epithelial sheets are used to promote corneal surface reconstruction after the detection of limbal epithelial stem cell deficiency. The aim of this study was to evaluate a novel combination of limbal stem cells (LSCs) maintained on contact lenses (CLs) in the presence of a 3T3 feeder cell layer regarding preservation of stem cell phenotype and the potential use for future in vivo transplantation. METHODS: Limbal epithelial cells were isolated from rabbit cornea and cultured with 3T3 cells on CLs. The preservation of LSC phenotype was determined using p63α and ABCG2 immunostaining, whereas epithelial differentiation was evaluated using CK3 and CK19. The colony-forming assay was used to determine the percentage of LSCs in cultures. Finally, CLs seeded with PKH26-labeled LSCs were transferred to rabbit eyes after performing a surgical keratectomy, and the transition and phenotype of labeled cells on the corneal surface were evaluated in whole-mount corneas. RESULTS: Proliferation of individual limbal cells was observed on CLs with a 3T3 feeder cell layer, showing holoclone formation and retention of viable stem or progenitor cell phenotype. Finally, a higher transition of cultivated cells after a dual sequential CL transplantation to the ocular surface was observed, showing the preservation of the LSC phenotype in the corneal surface. CONCLUSIONS: Limbal cells cultivated on a CL carrier overlaying a 3T3 feeder layer are mitotically active and retain the LSC phenotype. This novel technique of using CLs as a carrier offers an easily manipulable and nonimmunogenic method for transferring LSCs for ocular surface reconstruction in patients with limbal epithelial stem cell deficiency.