02/20/2025
By Zhiyong Gu
Dr. Emmanuel (Manolis) Tzanakakis, professor and chair of Department of Chemical and Biological Engineering at Tufts University, will give a seminar titled, "Engineering Next-Generation Cellular Therapeutics: From Exosomes to Functional Modulation via Optogenetics".
Date: Feb. 27
Time: 3:30 to 4:45 p.m.
Location: Shah Hall, Room 303
Abstract:
The repair and replacement of damaged tissues is an area of enormous potential for cellular therapies. In this context, molecular tailoring and bioprocessing are key components in cell therapeutics development for conditions such as heart disease and diabetes. Cardiomyocytes obtained from human pluripotent stem cells (hPSC) in scalable amounts are one example of such products. To this end, we have formulated xeno-free, fully defined media to support both stem cell propagation and differentiation. Moreover, a method was established for directing the fate of hPSCs in stirred suspension toward cardiac muscle in three separate stem cell lines. Greater than 85% of the resulting cells were positive for relevant markers such as cardiac troponin T, actinin, and NKX2.5. Electrophysiological analysis revealed that most contracting cells closely resembled ventricular cardiomyocytes.
We also explored the role of exosomes in the cardiogenic differentiation of stem cells. Exosomes collected at different developmental stages were analyzed by proteomics, identifying over 300 proteins at each stage, including key signaling molecules associated with heart development. Notably, stem cells treated with exosomes derived from hPSC-derived cardiomyocytes demonstrated a significant increase in their percentage expressing cardiac myosin compared to cultures without exosome treatment.
Further, we employed optogenetics to modify cardiac muscle cells and pancreatic insulin-producing beta cells for drug-free functional regulation. For example, cardiomyocytes were engineered to express a photoactivatable adenylyl cyclase (PAC) gene that permitted induction of enhanced contractility by blue light with no adverse effects. Correspondingly, in rodent and human beta cells, we showed photoregulation of cAMP with physiologically relevant kinetics. This resulted in more than a two-fold increase in glucose-stimulated insulin secretion upon illumination. Implantation of these engineered cells into diabetic mice led to significant improvement in glucose tolerance.
These findings illustrate the potential of pluripotent cell bioprocessing and optogenetic technologies in the development of advanced cell-based therapies.
Biography: Emmanuel Tzanakakis is professor of chemical and biological engineering at Tufts University. He is also a member of the Clinical and Translational Science Institute of the Tufts Medical Center, and of the Cell, Molecular and Developmental Biology of the Tufts Graduate School of Biomedical Sciences. He earned his Ph.D. in chemical engineering from the University of Minnesota and did his postdoctoral training at the Stem Cell Institute of the University of Minnesota and at the Diabetes Center of the University of California, San Francisco. His laboratory's research interests are in the area of stem cell engineering, particularly for diabetes and heart disease applications. Implementing a combination of experiment- and computation-based approaches, the overarching goal of his research is the realization of the potential of stem cells in regenerative medicine.