The rationale driving this project is that there are natural cells in the body that are known to express peripheral tissue antigens (pTAs) and induce tolerance to self-reactive lymphocytes in vivo. We have discovered that MSCs also express these pTAs and can maintain this expression during ex vivo processing unlike other pTA expressing cells. We hypothesize that the expression of self antigens by MSCs is essential for the therapeutic efficacy of cell transplants in models of autoimmune disease, and therefore may be amenable to ex vivo monitoring/optimization to create a tailored cell therapy. The objectives are to evaluate the relevance of pTA expression in the immune response to MSCs, both in vitro and in vivo, and image these cell grafts during the treatment of an antigen-specific model of intestinal autoimmunity. The long-term goal is to evaluate this use of a unique form of antigen presentation by MSCs as a therapeutic mode of action and essentially create a new drug class based on antigen-specific stem cell grafts.

Public Health Relevance

This is a Mentored Research Scientist Development Award application for Dr. Biju Parekkadan a biomedical engineer by training with specialization in cell-based therapy. He has developed new treatment approaches that harness the natural functions of mesenchymal stem cells (MSCs) for therapy. Recently, he has discovered a new function of MSCs that has significant relevance to the fields of autoimmunity and transplantation. As a recently appointed postdoctoral fellow, Dr. Parekkadan submits this five-year career development plan under the mentorship of Drs. Martin L. Yarmush, the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School and the director of the Center for Engineering in Medicine, Ralph Weissleder, Professor of Radiology at Harvard Medical School and the director of the Center for Molecular Imaging Research at the Massachusetts General Hospital and Diane Mathis, Professor of Immunology and Immunogenetics at Harvard Medical School. The award includes extensive: (1) hand-on training in radiological and immunological studies of cell transplants in vivo, (2) academic courses and seminars, and (3) guidance of a selected advisory committee towards the future large-scale research projects.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
Project #
Application #
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Tosi, Lorenzo; Sridhara, Viswanadham; Yang, Yunlong et al. (2017) Long-adapter single-strand oligonucleotide probes for the massively multiplexed cloning of kilobase genome regions. Nat Biomed Eng 1:
Lee, Jungwoo; Heckl, Dirk; Parekkadan, Biju (2016) Multiple genetically engineered humanized microenvironments in a single mouse. Biomater Res 20:19
Shen, Keyue; Luk, Samantha; Elman, Jessica et al. (2016) Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis. Sci Rep 6:21239
Lee, Jungwoo; Kohl, Nathaniel; Shanbhang, Sachin et al. (2015) Scaffold-integrated microchips for end-to-end in vitro tumor cell attachment and xenograft formation. Technology (Singap World Sci) 3:179-188
Milwid, Jack M; Elman, Jessica S; Li, Matthew et al. (2014) Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators. Mol Ther 22:999-1007
Fletcher, Anne L; Elman, Jessica S; Astarita, Jillian et al. (2014) Lymph node fibroblastic reticular cell transplants show robust therapeutic efficacy in high-mortality murine sepsis. Sci Transl Med 6:249ra109
Elman, Jessica S; Murray, Ryan C; Murray, Ryan M et al. (2014) Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. PLoS One 9:e89882
Shen, Keyue; Luk, Samantha; Hicks, Daniel F et al. (2014) Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays. Nat Commun 5:5662
Bersani, Francesca; Lee, Jungwoo; Yu, Min et al. (2014) Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models. Cancer Res 74:7229-38
Shen, Keyue; Lee, Jungwoo; Yarmush, Martin L et al. (2014) Microcavity substrates casted from self-assembled microsphere monolayers for spheroid cell culture. Biomed Microdevices 16:609-15

Showing the most recent 10 out of 21 publications