Abstract
Stem cells (SCs), the undifferentiated biological cells, have the infinite capacity to self-renew and the pluripotent ability to differentiate. SCs and their derived products offer great promise for biomedical applications such as cell therapy, tissue engineering, regenerative medicine and drug screening. However, the clinical applications of SCs require a large amount of SCs with high quality and the number of SCs from their tissue resources is very limited. Large-scale expansion is needed to generate homogeneous SCs with good biological characteristics for clinical application. This necessitates a bioreactor system to provide controllable and stable conditions for stem cell (SC) culture. Traditional methods of bioreactor for maintenance and expansion of cells rely on two-dimensional (2-D) culture techniques, leading to loss self-renewal ability and differentiation capacity upon long-term culture. New approaches for SC expansion with bioreactor employ three-dimensional (3-D) cell growth to mimic their environment in vivo. In this review, we summarize the application of bioreactors in SC culture.
Highlights
SCs, a type of cells with infinite proliferation capacity and pluripotent differentiation potential, can roughly be categorized as embryonic stem cells (ESCs), adult stem cells (ASCs) and induced pluripotent stem cells
With the emergence and development of gene editing technology, the mutated gene in the SCs of patients can be corrected and the edited SCs are transplanted to replace the mutated SCs in these patients, which represents a direction in SC treatment [1, 2]. 2) Construction of tissues or organs: SCs can be used as seed cells and cultured with tissue compatibility biomaterials to construct tissues or organs which are used to repair the lesion of tissues or organs [3, 4]. 3) Toxicology and drug screening: SCs provide a basis for the studies on the toxicology and pharmacokinetics of a new drug at the cell level, which reduces the requirement for animal test or clinical test [5]
In the hollow fiber bioreactor, the culture chamber consists of thousands of hollow fibers, and each hollow fiber is perfused with culture medium for cell growth, the space between hollow fibers is known as external chamber, and cells are adherent to the external wall of hollow fibers and can take nutrients from the inner chamber
Summary
SCs, a type of cells with infinite proliferation capacity and pluripotent differentiation potential, can roughly be categorized as embryonic stem cells (ESCs), adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs). It is difficult to compare the performance of different bioreactors in SC culture based on expansion rates and/or achievable cell densities, accumulating data from available studies using different bioreactors indicate that the development of bioreactors is very important step for the expansion of different SCs including the suspension and adherent SCs [9, 10]. Novel systems and approaches are still needed to offer suitable strategies to expand SCs in vitro Bioreactors such as stirred tank [11, 12], wave-rocking [13, 14], rotating wall vessel [15, 16] and hollow fiber bioreactors [17, 18] have been recently studied for SC expansion. We summarize these bioreactors widely used for expansion of SCs according to their rationality, characteristics and mode in SC culture
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