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Human-Origin iPSC-Based Recellularization of Decellularized Whole Rat Livers
Aylin Acun1,2,3, Ruben Oganesyan1,2, Maria Jaramillo1,2
1Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, Boston, MA 02114, USA.
To improve liver regeneration, induced pluripotent stem cells (iPSCs) were cultured in decellularized liver scaffolds. This native 3D microenvironment enhanced iPSC differentiation into mature, functional hepatocyte-like cells, offering a promising alternative to transplantation.
Area of Science:
- Regenerative Medicine
- Bioengineering
- Stem Cell Biology
Background:
- End-stage liver disease causes high mortality, with liver transplantation limited by donor organ scarcity.
- Decellularized liver scaffolds offer a potential solution by providing a structural matrix for regenerating functional liver tissue.
- Patient-specific cells, like induced pluripotent stem cells (iPSCs), are crucial for avoiding immune rejection but often lack full maturity.
Purpose of the Study:
- To investigate the role of the native 3D liver microenvironment in enhancing the differentiation of iPSCs into mature hepatocyte-like cells.
- To assess if culturing iPSCs within decellularized liver scaffolds improves cell functionality and maturity compared to standard differentiation methods.
Main Methods:
- Decellularization of rat liver organs to create a biological scaffold.
- Seeding of induced pluripotent stem cells (iPSCs) into the decellularized liver scaffolds.
- Perfusion culture of iPSCs within the scaffold to promote differentiation into hepatic lineages within the native microenvironment.
Main Results:
- iPSC differentiation into hepatocyte-like cells was significantly enhanced within the decellularized liver scaffold.
- The resulting cells exhibited higher expression of mature hepatocyte markers, including CYP450 enzymes, and lower expression of fetal markers (e.g., AFP).
- Gene expression profiles during differentiation more closely resembled native liver development.
Conclusions:
- The native 3D liver microenvironment plays a critical role in promoting the development of mature, functional hepatocyte-like cells from iPSCs.
- This bioengineering approach using decellularized scaffolds holds promise for generating patient-specific liver cells for therapeutic applications.
- Enhanced differentiation within the native matrix could overcome limitations of current iPSC-based regenerative strategies for liver disease.
