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Background
Hepatic Regenerative Medicine Laboratory is state-of-the-art facility for research and development of novel regenerative therapy for transplant-free management of liver disease. It consists of wellequipped cell and organ culture laboratory to support the bench side research and development of new therapy to augment native liver repair and regeneration. The laboratory also has a cGMP (current good manufacturing practice)-compliant state-of-art clean room facility for the manufacturing of clinical-grade cell therapy products for patient care.
Vision of Lab:
- To elucidate the mechanisms underlying regeneration failure in advanced liver diseases.
- To explore the interplay between the liver and bone marrow to deepen our understanding of liver regeneration.
- To pioneer novel cell-based therapies to enhance liver regeneration
Research summary
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Liver regeneration
Our research concentrates on understanding how the liver regenerates in setting of acute and chronic liver injury and how this process get impaired leading to liver failure. We also focus to identify the potential target involve in regeneration failure and develop cell- based therapy to augment native liver regeneration
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Aims and areas of interest
Basic research :
By understanding what controls liver regeneration acute and chronic liver injury our group aims to be able to promote healthy liver regeneration and prevent liver failure. We employ a multifaceted approach that includes studying the intricate relationship between the liver and bone marrow, developing cell-based therapies like mesenchymal stem cell therapy and macrophage therapy, and exploring bioengineered strategies. These strategies include CAR-Macrophage therapy and bioartificial liver support systems, all aimed at potentiating liver regeneration and addressing liver diseases comprehensively.Clinical Research :
Operating within a state-of-the-art cGMP lab, we are actively involved in developing mesenchymal stem cell therapy for clinical application. Our previous work in an animal model of Acute-on-Chronic Liver Failure (ACLF) showcased the efficacy of umbilical cord mesenchymal stem cell therapy in augmenting liver regeneration by preventing the bioenergetic exhaustion of monocytes.
Research facilities
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Ongoing Projects:
- To investigate gut-bone marrow axis in cirrhosis associated haematopoietic dysfunction (DST-SERB)
- Integrated functionomics approach to develop resolving macrophage therapy for augmenting resolution of liver injury and infection in acute- on- chronic liver failure (ACLF) (ICMR)
- Extracorporeal Liver Macrophage Assist Device (ELMAD) for alleviating sepsis in acute liver failure (DST-SERB)
Selected Publications:
- Maheshwari, D., Kumar, D., Jagdish, R. K., Nautiyal, N., Hidam, A., Sehgal, R., ... & Kumar, A. (2022). Bioenergetic failure drives functional exhaustion of monocytes in acute-on-chronic liver failure. Frontiers in Immunology, 13, 856587.
- Kumar, D., Maheshwari, D., Nautiyal, N., Shubham, S., Rooge, S., Anand, L., ... & Sarin, S. K. (2022). Defects in energy metabolism are associated with functional exhaustion of bone marrow mesenchymal stem cells in cirrhosis. American Journal of Stem Cells, 11(1), 12.
- Nautiyal, N., Maheshwari, D., Tripathi, D. M., Kumar, D., Kumari, R., Gupta, S., ... & Sarin, S. K. (2021). Establishment of a murine model of acute-on-chronic liver failure with multi-organ dysfunction. Hepatology international, 15(6), 1389-1401.
- Shubham, S., Kumar, D., Rooge, S., Maras, J. S., Maheshwari, D., Nautiyal, N., ... & Sarin, S. K. (2019). Cellular and functional loss of liver endothelial cells correlates with poor hepatocyte regeneration in acuteon-chronic liver failure. Hepatology International, 13, 777-787.
- Nautiyal, N., Maheshwari, D., Kumar, D., Rao, E. P., Tripathi, D. M., Mohanty, S., ... & Kumar, A. (2023). Early loss of bone marrow hematopoietic stem cells drives regeneration failure in cirrhosis. Published online March 2023. doi:10.21203/rs.3.rs-3250973/v1
- Patent: A method of infusion of bone marrow mononuclear cells to rejuvenate bone marrow stem cells (Patent Application no.: 20221108925).
