image: Human induced pluripotent stem cell (hiPSC)-derived skin organoids (SKOs) generate sweat and sebaceous glands when differentiated using air-liquid interface conditions. a) Representative bright-field images of SKOs generated from the P112 hiPSC line on the transwell at Day 90. Red arrows indicate the hair follicles (HFs), and black asterisks indicate the cartilaginous parts. b and c) Representative hematoxylin and eosin (H&E) staining images, from the same SKOs shown in part a, confirm the presence of hair shafts (HS, dashed arrows), dermal papilla (DP), and sebaceous glands (blue arrows). c) Representative bright-field images of SKOs generated from the P112 hiPSC line on the transwell at Day 120, red arrows indicate the HFs. e and f) Representative H & E staining images, from SKOs confirm the presence of HS, DP (dashed arrows), and sweat glands (black arrowheads). g-k) Representative immunostaining images of SKOs on transwell. Dashed yellow boxes indicate the magnified regions. g, and h) Keratin 17 (KRT17) staining confirms the presence of HFs within the SKOs as indicated by white asterisks. Neuron specific class III beta-tubulin (TUJ1) staining confirms the innervation of the dermal layer at Day 120. i, and j) Immunostaining analysis confirms the presence of smooth muscle actin (SMA) positive arrector pili muscles and Keratin 20 (KRT20) positive Merkel cells next to the HFs. The blue color indicates cell nuclei stained with 4′,6 diamidino-2-phenylindole (DAPI). In parts i and j, the white asterisks, yellow arrowheads, and white arrowheads indicate HFs, Merkel cells, and arrector pili muscles respectively. Scale bars are 500 µm for the whole organoid sections in parts a, b, d, e, g, h, i, j, and k, and 100 µm for parts c, f, and inserts in parts g, h, i, j, and k.
Credit: Burns & Trauma
A pioneering study has unveiled the transformative role of air-liquid interface (ALI) culture in the morphogenesis of hair follicles within skin organoids derived from human-induced pluripotent stem cells (hiPSCs). This research not only sheds light on the intricate mechanisms of skin development but also sets a new benchmark in dermatological research, offering refined models for studying skin diseases and crafting innovative therapeutic solutions. ALI culture demonstrates unparalleled efficacy in promoting hair follicle development and maturation, presenting a cutting-edge platform for skin research and clinical advancements.
For decades, creating human skin models with physiological relevance has been a persistent challenge in dermatological research. Conventional approaches, such as rodent models and two-dimensional skin cultures, fail to replicate the complexity and functionality of human skin, particularly in aspects like appendage development. These gaps hinder progress in translating laboratory findings into effective clinical treatments. The scientific community has long recognized the urgent need for advanced skin models that authentically emulate human skin’s structure and function.
On January 16, 2025, a pivotal study (DOI: 10.1093/burnst/tkae070) published in the journal Burns & Trauma made remarkable progress in skin regeneration. Researchers discovered that employing an air-liquid interface (ALI) culture method significantly enhances hair follicle formation within hiPSC-derived skin organoids compared to traditional floating culture techniques. This breakthrough holds immense potential for advancing therapies for skin disorders and crafting next-generation skin regeneration solutions.
The research employed an ALI model with transwell membranes to cultivate hiPSC-derived skin organoids (SKOs), contrasting its efficacy with conventional floating culture methods. The results were striking—SKOs under ALI conditions exhibited superior hair follicle growth, both in quantity and structural complexity. These follicles were not only larger and more mature but also demonstrated features akin to natural hair shafts, closely mirroring in vivo hair follicle development. Moreover, ALI-cultured SKOs exhibited enhanced epidermal stratification and differentiation, signifying a more precise replication of human skin architecture. These findings underscore the promise of ALI culture in advancing skin organoid engineering, offering a sophisticated and functional platform for research and therapeutic development in dermatology.
"The use of ALI culture has proven to be a game-changer in the development of skin organoids," remarked the lead researcher. "The enhanced maturation and functionality of the hair follicles highlight the transformative potential of this method for dermatological research and regenerative medicine."
The implications of this study extend far beyond the lab. Enhanced skin organoids may revolutionize the study of skin diseases, enabling more accurate disease models and the development of novel treatments. Furthermore, the advancements in hair follicle development could pave the way for groundbreaking therapies addressing hair loss and other skin-related conditions. By enabling the creation of patient-specific skin analogs, this research heralds a future where personalized and highly effective therapeutic approaches redefine dermatological care.
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References
DOI
Original Source URL
https://doi.org/10.1093/burnst/tkae070
Funding information
Metro North Hospital and Health Service (MNHHS), Queensland Health, Queensland, Australia.
About Burns & Trauma
Burns & Trauma is an open access, peer-reviewed journal publishing the latest developments in basic, clinical, and translational research related to burns and traumatic injuries, with a special focus on various aspects of biomaterials, tissue engineering, stem cells, critical care, immunobiology, skin transplantation, prevention, and regeneration of burns and trauma injury.
Journal
Burns & Trauma
Subject of Research
Not applicable
Article Title
The empowering influence of air-liquid interface culture on skin organoid hair follicle development
Article Publication Date
16-Jan-2025
COI Statement
The authors declare that they have no competing interests.