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Updated: Oct 7, 2025

Three-Dimensional Collagen Matrix Scaffold Implantation as a Liver Regeneration Strategy
Published on: June 29, 2021
Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue
Jiabin Zhang1,2, Hon Fai Chan3,4, Haixia Wang1
1Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Abstract:
Liver failure is a lethal condition with hepatocellular dysfunction, and liver transplantation is presently the only effective treatment. However, due to the limited availability of donors and the potential immune rejection, novel therapeutic strategies are actively sought to restore the normal hepatic architectures and functions, especially for livers with inherited metabolic dysfunctions or chronic diseases. Although the conventional cell therapy has shown promising results, the direct infusion of hepatocytes is hampered by limited hepatocyte sources, poor cell viability, and engraftment. Hence, this review mainly highlights the role of stem cells and progenitors as the alternative cell source and summarizes the potential approaches based on tissue engineering to improve the delivery efficiency of cells. Particularly, the underlying mechanisms for cell therapy using stem cells and progenitors are discussed in two main aspects: paracrine effect and cell differentiation. Moreover, tissue-engineering approaches using cell aggregates and decellularized liver scaffolds for bioengineering of functional hepatic constructs are discussed and compared in terms of the potential to replicate liver physiological structures. In the end, a potentially effective strategy combining the premium advantages of stem cell aggregates and decellularized liver scaffolds is proposed as the future direction of liver tissue engineering and regeneration.
Insights
Stem cells and tissue engineering offer promising alternatives to liver transplantation for liver failure. These approaches aim to regenerate liver function by improving cell delivery and engraftment for better therapeutic outcomes.
Area of Science:
- Regenerative Medicine
- Hepatology
- Biomedical Engineering
Background:
- Liver failure necessitates transplantation due to limited donor organs and immune rejection.
- Conventional hepatocyte therapy faces challenges with cell source, viability, and engraftment.
- Novel strategies are crucial for restoring liver architecture and function, especially for metabolic diseases.
Purpose of the Study:
- To review stem cells and progenitors as alternative cell sources for liver regeneration.
- To summarize tissue engineering approaches for enhancing cell delivery and engraftment.
- To discuss mechanisms of stem cell therapy (paracrine effects, differentiation) and tissue engineering strategies.
Main Methods:
- Review of current literature on stem cell therapy and tissue engineering for liver regeneration.
- Analysis of stem cell mechanisms including paracrine effects and differentiation potential.
- Comparison of tissue engineering methods: cell aggregates versus decellularized liver scaffolds.
Main Results:
- Stem cells and progenitors show potential as viable alternatives to hepatocytes.
- Tissue engineering strategies, including cell aggregates and decellularized scaffolds, can improve cell delivery and functional construct bioengineering.
- Combining stem cell aggregates with decellularized liver scaffolds presents a promising future direction.
Conclusions:
- Stem cell-based therapy and advanced tissue engineering are key to overcoming limitations of liver transplantation.
- Optimizing cell delivery and engraftment through tissue engineering is critical for successful liver regeneration.
- A combined strategy of stem cell aggregates and decellularized scaffolds offers a potent approach for future liver tissue engineering and regeneration.

