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Principal Investigator: Kristina Roberts
Organization: STEMCULTURES, LLC
Fiscal Year: 2024
Award: $826,379
Funding agency: National Institute of General Medical Sciences
Scientific Abstract:
The frequent use of fetal bovine serum (FBS) to support cell cultures is challenged by lot-to-lot variability, supply
constraints, pathogen contaminants and ethical questions. These issues have increased significance due to the
burgeoning use of FBS in cell research and therapy development. FBS has been used for over a century to
culture cells, but with the need to define culture conditions for efficient manufacturing, along with modern
approaches to control delivery of key molecules, many of the problems associated with FBS use can now be
alleviated. The need to reduce animal products is critically important, as is the need to use human growth factors
to optimize human cell growth. The company StemCultures specializes in controlling the growth factor (GF)
component of cell culture media. Our goal is to replace FBS GFs with a bioengineered DISCTM (Defined Insert
for Sustainable Culture) device providing controlled-release human recombinant GFs. The advanced cell
manufacturing DISCTM device will address concerns about FBS and improve the reproducibility of cell production.
In this application we will develop a DISCTM device for growth of human retinal pigment epithelial (RPE) cells.
Human RPE was selected as a testbed for FBS replacement as these cells are a vanguard for stem cell
replacement therapy in the US, Europe and Asia. A barrier to reducing FBS use is the lack of knowledge about
the GF content of FBS that is critical for growth of the RPE cell product. We will measure levels of FBS GFs that
stimulate human RPE cell proliferation. Selected recombinant human GFs will be encapsulated in controlled-
release GF microbeads that provide a standardized growth signal over time, to replace the variable levels of
bovine GFs provided by FBS with defined levels of native human recombinant GFs. The GF microbeads will be
assessed in a factorial design experiment to identify microbead combinations that support RPE cell growth at a
reduced level of FBS. The microbead combination that supports RPE cell growth without FBS or at the lowest
level of FBS will be packaged in a Defined Insert for Sustainable Culture (DISCTM) device to simplify RPE cell
manufacture. The DISCTM will be manufactured as a commercial product marketed to reduce FBS dependence
of the commercially important RPE cells. Future work will apply the microbead/DISCTM platform strategy to
reduce FBS dependence of other cell types. The company StemCultures (SCL) routinely manufactures
microbeads and DISCsTM for sustained release of GFs in culture media and the co-located Neural Stem Cell
Institute (NSCI) has extensive RPE cell culture expertise. The SCL-NSCI collaboration successfully completed
Phase 1 aims, in preparation to make Phase 2 goals highly feasible.
Terms: <Animals><Asia><Biomedical Engineering><Blood Serum><Bovine Species><Cardiac Muscle Cells><Cardiac Myocytes><Cardiocyte><Catalogs><Cattle><Cell Body><Cell Communication and Signaling><Cell Components><Cell Culture Techniques><Cell Cycle><Cell Division Cycle><Cell Signaling><Cell Structure><Cells><Cellular Expansion><Cellular Growth><Cellular Structures><Collaborations><Collection><Complex><Culture Media><Cultured Cells><Cyclic GMP><Data><Dependence><Development><Development and Research><Devices><ELISA><EPC-1 protein><Encapsulated><Endotoxins><Enzyme-Linked Immunosorbent Assay><Epithelial Cell Proliferation><Epithelial Receptor Cell><Ethics><Europe><Experimental Designs><Feedback><Fetal Reduction><Future><Generalized Growth><Goals><Growth><Growth Agents><Growth Factor><Growth Substances><Guanosine Cyclic Monophosphate><Heart Muscle Cells><Heart myocyte><Human><Hydrogels><Intracellular Communication and Signaling><Knowledge><Life><Manufacturer><Marketing><Measures><Mesenchymal Progenitor Cell><Mesenchymal Stem Cells><Mesenchymal progenitor><Mesenchymal stromal/stem cells><Methods><Microbeads><Microspheres><Modern Man><Modernization><Multifetal Pregnancy Reduction><Neural Stem Cell><Outer pigmented layer of retina><PEDF><Pathway interactions><Phase><Pigment cell layer of retina><Pigmented layer of retina><Predictive Factor><Preparation><Production><Proliferating><Protein-Free Media><Proteins Growth Factors><Proteomics><R & D><R&D><Recombinant Growth Factor><Recombinants><Reproducibility><Research><Retinal Pigment Epithelium><Retinal pigment epithelial cells><Risk><STTR><Sampling><Selective Fetal Terminations><Serum><Serum-Free Culture Media><Serum-Free Media><Signal Transduction><Signal Transduction Systems><Signaling><Small Business Technology Transfer Research><Source><Standardization><Sterility><Stimulus><Structure of retinal pigment epithelium><Supporting Cell><T-Cells><T-Lymphocyte><Testing><Time><Tissue Growth><Viral><Work><Writing><bio-engineered><bio-engineers><bioengineering><biological engineering><biological signal transduction><bovid><bovine><cGMP><cardiomyocyte><catalog><cell culture><cell cultures><cell growth><cell replacement therapy><cell replacement treatment><cell type><clinical lot><commercial launch><commercial product launch><commercialization><controlled release><cow><develop therapy><developmental><early PDL protein><early population doubling level cDNA-1 protein><early population doubling level protein><enzyme linked immunoassay><ethical><fetal bovine serum><growth media><human progenitor cell derived><human stem cell-derived><improved><intervention development><manufacture><mesenchymal stromal progenitor cells><mesenchymal-derived stem cells><nerve stem cell><neural precursor><neural precursor cell><neural progenitor><neural progenitor cells><neuron progenitors><neuronal progenitor><neuronal progenitor cells><neuronal stem cells><neuroprogenitor><ontogeny><pathogen><pathway><pigment epithelium-derived factor><preparations><progenitor cell replacement><research and development><retinal stimulation><stem cell replacement><sterile><therapy development><thymus derived lymphocyte><transcriptomics><treatment development>