In addition to its annual lectures, ChBE hosts a weekly seminar throughout the year with invited lecturers who are prominent in their fields. Unless otherwise noted, all seminars are held on Wednesdays in the Molecular Science and Engineering Building ("M" Building) in G011 (Cherry Logan Emerson Lecture Theater) at 4:00 p.m. Refreshments are served at 3:30 p.m. in the Emerson-Lewis Reception Salon.

______________

Molecular and Systems Biology approaches in stem engineering and regenerative medicine

Cardiovascular disease is the leading cause of mortality worldwide. Regarded as the therapeutic gold standard, treatment with autologous grafts suffers from several technical and patient-related risks. Tissue engineered small diameter blood vessels may provide a promising alternative solution as replacement grafts. In this study, we employed adult and induced pluripotent stem cells to engineer fully functional vascular grafts that were implanted into the arterial circulation of a physiologically relevant ovine animal model. I will present results on the development of strategies to improve the quality and function of adult mesenchymal stem cells (MSC), which suffer from loss of cell function due to donor aging or culture senescence.

Our laboratory recently showed that MSC originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. This is a major concern, as the patients most likely to suffer from cardiovascular disease are elderly. Notably, we discovered that delivery of a single pluripotency associate transcription factor, Nanog could reverse the proliferation and differentiation potential of MSC from adult donors. I will present data supporting this claim and our efforts to understand the mechanism of how Nanog promotes myogenic differentiation and contractile function of senescent MSC. Molecular engineering strategies to reverse the effect of organismal aging aim at enhancing the potential of MSC from aged donors for cellular therapy and vascular tissue regeneration.

In the second part of my presentation I will focus on the development of a novel technology that we call LentiViral microArray (LVA) and its application in monitoring stem cell differentiation in real-time. The conventional tools for investigating gene expression such as qPCR are laborious, cost intensive and they cannot provide functional information on the pathways involved in biological processes. On the other hand, LVA provides live-cell, high-throughput monitoring of biological pathway activation during MSC differentiation. We employed LVA with a library of lentiviral vectors to monitor pathway activation during MSC differentiation into multiple lineages including smooth muscle, bone, fat or cartilage. This approach also allowed us to identify differences in the kinetics of pathway activation between MSC from different anatomic locations, despite their similar differentiation potential. Notably, the LVA enabled screening of small molecule libraries to discover novel pathways that are involved in stem cell differentiation along specific lineages. Our results suggest that the LVA is a tool with great potential to enhance understanding of stem cell fate specification as well as pathway regulation and drug discovery.