Controlled Apoptosis of Stromal Cells to Engineer Human Microlivers

Area of Science:

• Tissue Engineering
• Cell Biology
• Organogenesis

Background:

• Engineered tissue models utilize diverse cell types for physiological function.
• Precise control over cell-cell and cell-matrix interactions in 3D tissues is crucial for advancement.
• Current methods lack non-invasive control over cell populations within engineered tissues.

Purpose of the Study:

• To introduce a novel method for non-invasively controlling cell populations in engineered tissues.
• To investigate the transient contribution of stromal cells to the stability and function of primary human hepatocytes.
• To demonstrate the utility of controlled apoptosis in studying 3D tissue biology.

Main Methods:

• Development and application of CAMEO (Controlled Apoptosis in Multicellular tissues for Engineered Organogenesis) for non-invasive cell elimination.
• Creation of 3D hepatic microtissues incorporating primary human hepatocytes and fibroblasts.
• Assessment of liver functions including protein secretion and drug detoxification in engineered microtissues.

Main Results:

• CAMEO successfully enabled non-invasive, controlled elimination of genetically engineered cells from pre-established cultures.
• 3D hepatic microtissues showed enhanced phenotypic stability and spheroid formation with transient fibroblast interaction.
• Fibroblast contribution was found to be transient, yet essential for supporting multiple axes of liver function.

Conclusions:

• CAMEO provides a versatile platform for precise cell manipulation in engineered tissues.
• Stromal cell interactions are transiently critical for maintaining liver function in engineered hepatic models.
• This technology has broad applications in understanding organoid models and developing artificial tissue grafts.