İnsan indüklenmiş pluripotent kök hücre kaynaklı lakrimal bez organoidlerinin farklılaşma verimliliğinin arttırılması

The lacrimal gland (LG), also known as the tear gland, maintains homeostasis on the ocular surface by secreting electrolytes and proteins creating the aqueous layer of the tear film. As the main exocrine gland of the eye, it lubricates and protects the eye by the production of lacrimal fluid. Loss of function due to damage to the LG adversely affects eye health and vision quality. Although a large part of the human population is affected by eye diseases based on functional disorders in the LG such as dry eye disease, studies on human LG formation and development are limited. The LG is a structure that develops by branching, and it reaches its structural and functional maturity only when this process is completed, similar to salivary or mammary glands. In this study, human induced pluripotent stem cells (hiPSCs) were differentiated into cells with characteristics of LG in vitro by recapitulating budding and branching morphogenesis. Branching was stimulated via exogenous FGF10 and BMP7 proteins aiming to increase the differentiation efficiency. As an additional approach, the LG models were developed under dynamic conditions using microfluidic platforms to better mimic the native environment and develop more realistic LG models. In this context, the effects of this stimulation were examined at the RNA and protein levels of gene expressions. The results suggest that budding and branching development could be induced in vitro using exogenous supportive proteins. Additionally, developed models could be improved using dynamic conditions and these platforms could be used as a potential platform for therapeutic approaches.