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Intrahepatic Injection (IHI) of Cellular Therapy and Stem Cells: A Therapeutic Approach for Liver Disease

Intrahepatic Injection (IHI) of Cellular Therapy and Stem Cells, particularly mesenchymal stem cells (MSCs), is emerging as a promising strategy for treating liver diseases such as cirrhosis, liver failure, and autoimmune hepatitis (AIH). This approach aims to restore liver function by promoting regeneration, reducing fibrosis, and modulating immune responses.

Mechanisms of Action

1. Regenerative Potential:
   • MSCs differentiate into hepatocyte-like cells and secrete growth factors (e.g., HGF, VEGF) to stimulate endogenous liver repair158.
   • Paracrine effects reduce inflammation and inhibit hepatic stellate cell activation, curbing fibrosis38.
2. Immunomodulation:
   • MSCs regulate T-cell activity (e.g., increasing Treg cells, reducing Th17 cells) to mitigate autoimmune damage in conditions like AIH45.
3. Engraftment Challenges:
   • Intrahepatic delivery improves cell homing compared to peripheral injection, though cell entrapment in the lungs/spleen remains a hurdle46.
   • Hypoxic preconditioning and early-passage cells enhance engraftment efficiency4.

Clinical Applications

1. Liver Cirrhosis:
   • Allogeneic MSCs (via deep vessel injection) show superior survival benefits over autologous stem cells, reducing MELD scores by ~30%14.
   • Trials report improved albumin, bilirubin, and ascites resolution58.
2. Liver Failure:
   • MSC therapy combined with plasma exchange boosts survival rates (HR = 0.68 for allogeneic cells)1.
3. Autoimmune Hepatitis (AIH):
   • Menstrual blood-derived MSCs and dental pulp stem cells reduce hepatocyte apoptosis in preclinical models5.

Administration Protocols

• Route:
  • Intrahepatic artery or intrasplenic vein injections are preferred for targeted delivery246.
  • Peripheral vein injections risk pulmonary entrapment4.
• Dose:
  • Typical doses range from 0.5–2 × 10⁷ cells/kg46.
• Frequency:
  • Single deep vessel injections outperform multiple peripheral doses16.

Efficacy and Safety

Aspect	Findings
Survival	72-week survival increased by 25–40% in HBV-related liver failure18.
Fibrosis	Reduced collagen deposition in 60–70% of cirrhosis patients37.
Safety	Low adverse events; rare risks include hepatorenal syndrome7.

Challenges and Future Directions

1. Standardization:
   • Variable protocols (cell dose, source, route) hinder comparability67.
2. Long-Term Efficacy:
   • Benefits may wane after 6 months; repeated injections or adjuvant therapies (e.g., NAD+ precursors) are under study57.
3. Innovative Strategies:
   • Exosome-based therapies and iPSC-derived hepatocytes aim to bypass engraftment issues38.

Conclusion

Intrahepatic Injection (IHI) of Cellular Therapy and Stem Cells offers a viable alternative to liver transplantation for advanced liver diseases. While allogeneic MSCs and targeted delivery methods yield the best outcomes, standardized protocols and long-term safety data are critical for clinical adoption.

Consult with Our Team of Experts Now!
At DrStemCellsThailand (DRSCT)‘s Anti-Aging and Regenerative Medicine Center of Thailand, we specialize in advanced Cellular Therapy and Stem Cells for liver regeneration. For personalized treatment plans, consult our experts today!

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References

1. Meta-analysis on MSC therapy for liver failure (2024)
2. Adipose-derived MSC trial for cirrhosis (2020)
3. Cell therapy challenges in CLD (2015)
4. Clinical application of stem cells in cirrhosis (2021)
5. Stem cell therapy for liver disease (2024)
6. Cellular therapy review (2014)
7. Risks and efficacy of MSC therapy (2023)
8. MSCs in chronic liver disease (2019)