Abstract: Cellular therapies are emerging as a standard approach for the treatment of several diseases. However, realizing the promise of cellular therapies across the full range of treatable disorders will require large-scale, controlled, reproducible culture methods.  Adjusting methods developed from proof-of concept studies are necessary for the large-scale application of many cell products. Bioreactor systems offer the scale-up and monitoring needed, but standard stirred bioreactor cultures do not allow for the real-time regulation of key nutrients in the medium. Enrichment and cell processing characterization methods must also be developed.  Beta cells and human iPS cells were aggregated and cultured for 3 weeks as a model of manufacturing a mammalian cell product, as these cells are particularly sensitive to nutrient levels in the environment.  Glucose levels are particularly important for the differentiation, function and survival of beta cells, since they are sensitive to both high and low concentrations of this key nutrient.  For these cultures, even when glucose levels were increased to prevent depletion between feedings, dramatic fluctuations in glucose levels were observed. Continuous feeding eliminated fluctuations and improved cell expansion when compared with both static and stirred bioreactor culture methods. Further improvements in growth rates and differentiation profiles were observed after adjusting the feed rate based on calculated nutrient depletion, which maintained physiological glucose levels. Islet cell precursor isolation strategies and re-aggregation with support cell populations are being developed that minimize cell loss to shear forces and loss of cell-cell connections during processing. High throughput separation techniques used for processing hematopoietic stem cells reduced cell death by lowering shear and decreasing processing time.  Re-aggregation with mesenchymal cell populations improved post-separation viability and function in vivo.  The combined application of processing technologies improved cell yield and function as a basis for initiating clinical studies.

Bio: Meri Firpo is an Assistant Professor in the Stem Cell Institute and the Department of Medicine at the University of Minnesota, where she works on human embryonic stem cell biology, and transplantation therapies for diabetes.  She received her Ph.D. from the Cornell University Medical College Graduate School of Medical Sciences after completing a research project in the Developmental Hematopoiesis Laboratory at the Sloan Kettering Institute.  Her research at the Sloan Kettering Institute was focused on adult bone marrow stem cells.  She then did a postdoctoral fellowship at the National Jewish Institute for Immunology and Respiratory Medicine in Denver, Colorado, where she completed a project on generating hematopoietic stem cells from mouse embryonic stem (ES) cells in culture.  After returning to the Bay Area, Dr. Firpo did a second postdoctoral fellowship at the DNAX Research Institute for Molecular and Cellular Biology in Palo Alto, California, where she studied the development of the human hematopoietic system and human models of leukemia. 

Dr. Firpo went to the University of California San Francisco, where she directed the derivation of two of the human ES cell lines included in the National Institutes of Health Registry of Human Embryonic Stem Cells.  She has also derived new lines suitable for transplantation therapies using human feeder cells.  At the Univeristy of Minnesota, she is currently using human pluripotent stem cells as a model of human development, and differentiating human ES cells into functional tissues for transplantation. 

(via teleconference to SL165 at IUPUI)

~BME Faculty Hosts: Sherry Voytik-Harbin and Jenna Rickus~

***Coffee and juice will be provided at West Lafayette***