Stem cell bioprocessing: fundamentals and principles

Abstract

In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the 'omics' technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical-failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications.

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

“…The cultivation of hMSC is typically performed statically in standard systems like tissue culture flasks, culture trays, roller bottles, gas permeable blood bags or multi-well plates [19,40,41]. These mostly sterile disposable systems contain standard plastic surfaces.…”

Application of cell and biomaterial-based tissue engineering methods in the treatment of cartilage, menisci and ligament injuries

“…Cell growth depends on several important factors, including: temperature, pH, oxygen concentration, nutrients, growth factor/cytokine supply, concentration of metabolic waste and culture type (monolayer or 3D) [40]. Typically, cells are cultured at 37°C, although some reports suggest that oxidative stress can be reduced by culturing MSCs at 32°C [41].…”

The business of exploiting induced pluripotent stem cells

“…A positive response is evidently required to enable a product to successfully enter the market. However, if the response is negative because the product is too expensive, then the manufacturing process must be redesigned in order to reduce the cost of goods (COGs) sold to a level that is affordable to the health insurers [26]. If the new manufacturing process changes the original product specification then the regulators will consider that this is a new product and therefore require testing in clinical trials.…”