T-cadherin modulates hepatocyte functions in vitro
Salman R Khetani1, Alice A Chen, Barbara Ranscht
1Laboratory for Multiscale Regenerative Technologies, Massachusetts Institute of Technology, 77 Massachusetts Ave., E19-502D, Cambridge, MA 02139, USA.
Truncated-cadherin (T-cadherin) promotes liver cell function in lab cultures. Both cell-based and protein-based T-cadherin applications enhance hepatocyte function for tissue engineering.
Area of Science:
- Cell Biology
- Biochemistry
- Tissue Engineering
Background:
- Primary hepatocytes lose function and viability when isolated from the liver.
- Stromal cells can restore hepatocyte function in vitro, but the mechanisms are unclear.
- A functional genomic screen identified truncated-cadherin (T-cadherin) as a potential inducer of hepatic functions.
Purpose of the Study:
- To investigate the role of T-cadherin in maintaining hepatocyte function in vitro.
- To determine if T-cadherin can be used to enhance hepatocyte function for tissue engineering applications.
Main Methods:
- Coculturing primary rat hepatocytes with Chinese hamster ovary cells engineered to express T-cadherin.
- Culturing hepatocytes on substrata coated with recombinant T-cadherin protein (acellular presentation).
- Assessing liver-specific functions and viability of hepatocytes under different culture conditions.
Main Results:
- Cocultivation with T-cadherin-expressing cells significantly induced liver-specific functions in primary rat hepatocytes.
- Acellular presentation of T-cadherin enhanced hepatocyte functions in both pure cultures and cocultures.
- T-cadherin demonstrated a positive effect on hepatocyte phenotype modulation in vitro.
Conclusions:
- Both cellular and acellular T-cadherin presentation can effectively modulate hepatocyte phenotype in vitro.
- T-cadherin holds potential for tissue engineering applications aimed at restoring liver function.
- Further investigation into T-cadherin's role in vivo during embryogenesis and liver pathology is warranted.
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