Therapeutics and Applied Immunology Group

Mesenchymal stromal cells (MSCs) and their progeny perform a number of supportive functions to regulate the immunologic and hematopoietic stem cell niches in the bone marrow. We are interested in developing therapeutics and diagnostics that are inspired by MSC biology. Our work using bone marrow-derived MSCs is based on the fact that they have the ability to inhibit the proliferation and/or differentiation of specific immune cells to activating stimuli. We are developing a MSC-based extracorporeal bioreactor that exploits MSC-derived factors for use in inflammatory conditions. Based on our expertise, we are using an animal model of fulminant hepatic failure (FHF), which has a critical inflammatory component, as an in vivo test bed for device efficacy. Recent in vivo testing of our MSC-based extracorporeal bioreactor has demonstrated a significant survival benefit in treating FHF. Our current research integrates MSC function with bioengineered materials and systems for use in the field of regenerative medicine and applied immunology.

Examples of ongoing project include:

• Microfabricated biomaterials that serve as artificial lymphoid organ mimics
• Bioinformatics-guided identification of active factors from cell secretomes   
• Engineered tumor microchips to study tumor-stroma interactions
• Particle-based artificial cells
• Delivery devices for cellular secretions
• Pharmacokinetics and pharmacodynamics of cell therapy
• Antigen-based delivery systems for vaccines

Representative Publications

• Parekkadan B, Upadhyay R, Dunham J, Iwamoto Y, Mizoguchi E, Mizoguchi A, Weissleder R, Yarmush ML.  Bone Marrow Stromal Cell Transplants for the Treatment of Experimental Enterocolitis Requires Host CD11b+ Splenocytes. Gastroenterology 2011; 140: 966-975.
• Jiao, Y, Milwid JM, Yarmush ML, Parekkadan B.  A Mesenchymal Stem Cell Potency Assay.  Methods in Mol. Bio 2011; 677: 221-31.
• Yagi, H, Soto-Gutierrez, Nahmias Y, Goldwasser Y, Tompkins RG, Parekkadan B, Yarmush ML. Reactive Bone Marrow Stromal Cells Attenuate Systemic Inflammation via sTNFRI under the control of NFkB. Mol Therapy 2010; 18: 1857-64.
• Parekkadan B, Milwid JM.  Mesenchymal Stem Cells as Therapeutics. Ann Rev Biomed Eng 2010; 12: 87-117. (invited review)
• Yagi H, Parekkadan B, Suganuma K, Soto-Gutierrez A, Tompkins RG, Yarmush ML.  Long-Term Superior Performance of a Stem Cell/Hepatocyte Device for the Treatment of Acute Liver Failure. Tissue Eng 2009; 15(11): 3377-88.
• van Poll D, Parekkadan B, Cho C, Berthiaume F, Nahmias Y, Tilles AW, Yarmush ML.  Mesenchymal Stem Cell-Derived Molecules Modulate Cell Death and Regeneration In Vitro and In Vivo. Hepatology 2008; 47(5): 1634-1643.
• Parekkadan B, Tilles AW, Yarmush ML.  Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Autoimmune Enteropathy Independent of Regulatory T Cells. Stem Cells 2008;  26(7): 1913-1919.
• Parekkadan B, van Poll D, Suganuma K, Carter EA, Tilles AW, Yarmush ML.  Mesenchymal Stem Cell-Derived Molecules Reverse Fulminant Hepatic Failure. PLoS One 2007;2(9):  e941.