Differentiation of bone marrow-derived mesenchymal stem cells into multi-layered epidermis-like cells in 3D organotypic coculture.
The interactions of bone marrow-derived mesenchymal stem cells (MSCs) and their engrafted microenvironment are an integral part of signaling control of stem cell lineage commitment. We attempted to induce bone marrow-derived MSCs to undergo epidermal lineage differentiation by manipulating the biochemical, environmental and physical properties of culture conditions in an organotypic coculture model to simulate a skin-specific microenvironment. The induction medium was optimized by varying different biomolecular supplements in a basic stratification medium. A multi-layered epidermis-like structure was established when MSCs were cultured in an optimized induction medium on a contractible fibroblast-embedded collagen gel with an air-liquid interface. The commitment into epidermal lineage was further confirmed by the expression of early and intermediate epidermalization markers - keratin 10 and filaggrin in 90.67% and 80.51% of MSCs, respectively. This study not only highlights the possibility of in vitro control of MSCs into epidermal lineage, but also suggests the therapeutic potential of bone marrow-derived MSCs for skin regeneration.
Ma
Kun
K
NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, Singapore 117576, Singapore. g0500566@nus.edu.sg
Laco
Filip
F
Ramakrishna
Seeram
S
Liao
Susan
S
Chan
Casey K
CK
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D000078404:Epidermal Cells; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053550:Keratin-10 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D012038:Regeneration / Q000502:physiology; D046509:Tissue Culture Techniques
D015415:Biomarkers; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D053550:Keratin-10