Ma Kun, Laco Filip, Ramakrishna Seeram, Liao Susan, Chan Casey K
NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, Singapore 117576, Singapore.
Biomaterials. 2009 Jul;30(19):3251-8. doi: 10.1016/j.biomaterials.2009.02.025. Epub 2009 Mar 13.
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.
骨髓间充质干细胞（MSCs）与其植入的微环境之间的相互作用是干细胞谱系定向信号控制的一个组成部分。我们试图通过在器官型共培养模型中操纵培养条件的生化、环境和物理特性，模拟皮肤特异性微环境，诱导骨髓来源的间充质干细胞向表皮谱系分化。通过在基本分层培养基中改变不同的生物分子补充剂来优化诱导培养基。当间充质干细胞在优化的诱导培养基中，于具有气液界面的可收缩成纤维细胞包埋胶原凝胶上培养时，形成了多层表皮样结构。分别在90.67%和80.51%的间充质干细胞中检测到早期和中期表皮化标志物——角蛋白10和丝聚蛋白的表达，进一步证实了其向表皮谱系的定向分化。本研究不仅突出了体外将间充质干细胞控制为表皮谱系的可能性，还提示了骨髓来源的间充质干细胞在皮肤再生方面的治疗潜力。
