The cell biology and tissue engineering labs at HMRI are meant to support the investigators from other HMRI groups, and welcome inquiries from outside scientists about collaborative research.
Lab members include:
Marie Csete MD, PhD
Andrea Loewendorf PhD
Current funded research is focused on generating induced pluripotent stem cells (iPSC) from Alzheimer’s study participants and from healthy elderly control volunteers. The ongoing Alzheimer’s study led by Dr. Harrington’s group has amassed a huge data set of important changes in proteins and lipids in cerebrospinal fluid as a function of disease progression. But—the cellular source of these changes is completely unknown and Dr. Csete’s lab is using iPSC to address that question. Using the activated T cells of these very well-characterized study participants that can be acquired with a simple blood draw, a pure population of (nestin+) neural stem cells will be generated. Starting with this stem cell population, the different cell types of the brain will be differentiated: glia (astrocytes and microglia) and neurons. The first studies will be determining which cell type is the source of inflammatory lipids found in CSF of early AD subjects. We next hope to characterize the exosomes of glia and neurons from these subjects for lipid and microRNA changes as a function of AD status. Our hypothesis is that inflammatory lipids will be increased in glial exosomes of AD patients and that their microRNA pattern is enriched in anti-oncogenic microRNAs.
In collaboration with Dr. Robert Kloner, HMRI cardiologist, the iPS cells are being used to investigate how far cells from different donors have intrinsically different thresholds to stressors that typically occur during normal aging or stroke. Thus, we will compare iPS cells and their derivative from healthy aging study participants and those with AD for their tolerance of mild oxidative stress (associated with healthy aging). We will also examine the response of cells that are subjected to oxygen-glucose deprivation (mimicking stroke) at various stages of differentiation. We hypothesize that AD-iPS cells and their differentiated progeny are more susceptible to these stresses, and that cardiolipin-binding compounds being developed by Stealth will be protective in these stressed cells.
In another study, the lab is generating extracellular matrices from human placenta and testing its ability to promote growth of broad classes of stem cells in the lab. Several preparations have been made and the testing of stem cells and cell lines is underway. The first goal of this project is to make a surface coating that supports expansion of cell lines that are normally difficult to cultivate in the lab. In the long-term, we hope to use this product in experimental models of wound healing, with an eye toward translation.