at KU Leuven in Leuven, Belgium, joined a team of international scientists to study neurons in the human brain, finding that DNA is not identical in all neurons in the brain. These findings have major implications for treatment of brain disorders such as autism and schizophrenia.
Mayo Clinic Collaboration
In 2013, Cardio3 BioSciences received $5.5 million in regional government funds to produce the C-Cathez-intramyocardial injection catheter and the C-Cure Stem Cell treatment for treating patients with heart failure. The treatment had been developed at the Mayo Clinic’s Center of Regenerative Medicine in collaboration with Belgian researchers of the Cardiovascular Centre in Aalst, Belgium, and Cardio3 BioSciences. Before the procedure, stem cells are harvested from a patient’s hip, and the catheter is used to inject those stem cells into beating hearts. Since the catheter uses a curved needle with graded slots, it can target heart cells while limiting the loss of cells by preventing backflow. In early 2014, the U.S. Food and Drug Administration (FDA) announced that it had approved Phase III clinical trials involving 240 patients in multiple states for the use of this treatment on patients with heart failure. Clinical trials were also carried out at 40 hospitals in Europe and Israel.
Researchers and physicians engaged in stem cell research and therapies continue to perform groundbreaking work in the supportive environment of Belgium. The willingness of Belgian researchers to collaborate with other scientists in Europe and North America has resulted in increased knowledge of the ways that stem cell research can be used to save and improve human lives.
Elizabeth Rholetter Purdy
Independent Scholar
See Also: Mayo Clinic; Minnesota; University of Cambridge; University of Minnesota.
Further Readings
Banchoff, Thomas F. Embryo Politics: Ethics and Policy in Atlantic Democracies. Ithaca, NY: Cornell University Press, 2011.
“Belgian Scientists Repair Bones With New Stem Cell Technique.” http:/www.cbsnews.com/news/belgian-scientists-repair-bones-with-new-stem-cell-technique (Accessed March 2014).
Cardio3 Biosciences. http:/www.c3bs.com/en (Accessed March 2014).
Cedric Blanpain Lab. http://blanpainlab.ulb.ac.be/research_main.html (Accessed March 2014).
Moran, Mark. “Historical Concept of Brain Death Still Makes Waves Today.” Neurology Today, v.5/7 (July 2008).
“The Reality of Human Stem Cell Research in Europe.” http:/www.esf.org/media-centre/ext-single-news/article/the-reality-of-human-stem-cell-research-in-europe-621.html (Accessed March 2014).
Steinhoff, Gustav, ed. Regenerative Medicine From Protocol to Patient. New York: Springer, 2011.
Vermylen, C., et al. “Haematopoietic Stem Cell Transplantation for Sickle Cell Anemia: The First 50 Patients Transplanted in Belgium.” Bone Marrow Transplantation, v.221 (1998).
Vlaams Instituut voor Biotechnologie. http:/www.vib.be/en/pages/default.aspx (Accessed March 2014).
Bioreactors
Bioreactors
79
81
Bioreactors
Bioreactors are controlled, closed systems used for the creation of cultures. They have many uses, ranging from the production of beer to more refined purposes such as creating large batches of stem cells of uniformly high quality. Microfluidic devices are another recent development similar to microbioreactors. Microfluidic devices and microbioreactors allow tight control and management of throughputs for better understanding of niches and more efficient drug screening. They also reveal paracrine/autocrine factors for enhanced control of differentiation. Both allow manipulation of the microenvironment through adjustment of cytokine gradients and flow rate.
Bioreactors have long been used in large-scale animal cell production, and converting them to stem cell generation is a matter of process engineering. Bioreactor engineering enables better modification and management of niches for maximum expansion, differentiation, and application of new cell-based medicines. Critical parameters include oxygen tension; 3-D scaffolds; physical forces such as mechanical, electrical, hydrodynamic force or strain; and flow shear. Different process outcomes and tissue-specific cell types require different bioreactor designs. What works for beer does not necessarily work for stem cells, regardless of type.
Stem cells are of two main types: pluripotent stem cells and adult stem cells. The pluripotent stem cells include both embryonic and induced pluripotent stem cells. Embryonic stem cells are pluripotent and can develop into all types of cells. This reprogramming of somatic cells is what causes them to become pluripotent. Adult stem cells, such as hematopoietic, neural, and mesenchymal stem cells, have a more limited differentiation potential and can only generate a subset of cells.
Stem cells hold great potential for biomedical applications across a wide spectrum, among them regenerative medicine, drug discovery, and cell therapy. Unfortunately, the current static tissue culture vessels, the Petri dish, can produce only small numbers of cells. Stem cell use is exceeding generation capacity of static vessels with cell counts reaching 1010–1012. Bioreactors need to be scalable and capable of quickly shifting the number and volume of cells they grow in order to provide the large numbers of stem cells that researchers need.
Stem cells require a regulated environment to grow properly. Because cells may be cultured either as free cells or aggregates fixated to solid substrates (such as the wall of the container) or in suspension, different bioreactor configurations are desirable. Bioreactors provide the necessary niche factors for proper growth into the appropriate cell configuration, regulating parameters such as oxygen, synthetic and decellularized extracellular matrix, paracrine/autocrine signaling, and physical forces such as mechanical and electrical forces and flow shear. The appropriate bioreactor offers precise control and recreation of niche factors by means of modulating or regulation of operation parameters. In this environment, the stem cells can expand and differentiate.
Stirred tank bioreactors produce free cells in suspension. This system is easy to scale up, provides a homogeneous culture environment, and is suitable for aggregate culture. However, it is subject to high shear stress. Another bioreactor type useful for cells or clusters in suspension is the rotary cell culture system (RCCS). The RCCS provides good mass transfer, controlled oxygenation, and low shear stress. However, the limited volume generated by the RCCS is relatively small and potentially inadequate for stem cell research. The wave bioreactor is suitable for hematopoietic stem cell culture and offers low shear stress, easy scalability, and gentle mixing, but it can be quite expensive.
For adherent cells, the microcarrier-based bioreactor may be either the stirred tank or the 4-D rotary cell culture system manufactured by Synthecon. The rotating wall bioreactor is a National Aeronautics and Space Administration (NASA) development
