Synergistic effects of mesenchymal stem cell secretome and Wnt10b on hair follicle regeneration in a 3D bioengineering model: a preclinical study
Year: 2025
Type: article
Abstract: Despite all advances, constructing functional hair follicles remains a significant clinical challenge. Building on recent advancements in mesenchymal stem cells secretome and Wnt signaling, we aimed to fabricate hair follicles in a 3D hydrogel scaffold and assess the effects of placenta-derived MSCs (PMSC) secretome and Wnt10b on follicle formation in ex vivo and in vivo models. A gelatin methacryloyl (GelMA) hydrogel scaffold was engineered via a 3D-printed We engineered a gelatin methacryloyl (GelMA) hydrogel scaffold using a 3D-printed polydimethylsiloxane mold to create a co-culture system for hair follicle biofabrication. Dermal papilla cells (DPCs) and epithelial cells from a donor were isolated and seeded into the scaffold to form microfollicles. We treated hair microfollicles with PMSC secretome, Wnt10b protein, or combination of both. The generated hair microfollicles were assessed using specific molecular and protein markers and then implanted into nude mice skin to investigate the hair growth in vivo. After three weeks of co-culturing, the group receiving both secretome and Wnt10b showed 90% cell aggregation and highest hair follicle formation rate at 28% (p < 0.0001). Immunofluorescent analysis revealed elevated expression levels of markers for DPCs and epithelial cells in formed hair follicles. Real-time PCR analysis indicated significantly enhanced expression of Wnt10b, Bmp6, Notch1 and Notch2 genes, particularly in the group receiving secretome and Wnt10b. Transplantation of GelMA hydrogels containing hair microfollicles into nude mice resulted in successful hair formation along with immunofluorescence and gene expression analyses showing marked increases in hair follicle growth markers. Our study demonstrates that the combination of PMSC-secretome and Wnt10b in a GelMA hydrogel scaffold effectively promotes hair follicle biofabrication and successful hair formation in vivo. However, the in vivo portion was limited by a small sample size (n = 3 per group), underscoring the need for larger-scale studies to confirm these findings. Constructing functional hair follicles has long been a clinical challenge. Our research explores the effects of placenta mesenchymal stem cells (PMSCs) secretome and Wnt10b protein within a gelatin methacryloyl (GelMA) scaffold for bioengineering hair microfollicles. We engineered a co-culture system using a GelMA hydrogel scaffold to form hair microfollicles, treated with PMSC secretome and Wnt10b. The results demonstrated enhanced hair follicle formation and elevated expression of hair growth markers following treatment with PMSC secretome and Wnt10b. This study advances hair regenerative therapies by successfully promoting hair follicle biofabrication and in vivo hair formation, offering potential solutions for treating hair loss.
Source: Stem Cell Research & Therapy
Authors: Amir Bajouri, Nasser Aghdami, Mohammad Ali Nilforoushzadeh
Institutions: Tehran University of Medical Sciences, Royan Institute
Language: English
Topic: Hair Growth and Disorders
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
OpenAlex ID: W4416736357