Abstract
The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration.
Highlights
Vast historical experience has been gathered around industrial use of diploid progenitor cell sources (e.g., Medical Research Council (MRC)-5, WI-38 cell types) as vaccine substrates since the 1960s, when developmental cell biology studies served as a basis for optimization of biological starting material selection [1,2,3,4,5,6,7]
Standard culture media (e.g., DMEM supplemented with fetal bovine serum) and culture conditions are sufficient for initiation of adherent lung tissue-derived progenitor cell cultures in vitro
In addition to the qualification of modern lung tissue-derived progenitor cell sources as vaccine substrates, optimization of regulatory aspects of potential direct therapeutic uses thereof is of equal high interest
Summary
Vast historical experience has been gathered around industrial use of diploid progenitor cell sources (e.g., MRC-5, WI-38 cell types) as vaccine substrates since the 1960s, when developmental cell biology studies served as a basis for optimization of biological starting material selection [1,2,3,4,5,6,7]. Ethical concerns with relation to the nature of starting materials should be taken into account, in particular with regard to the consideration of donor consent in the early days of diploid cell type establishment and use Such elements are important to take into consideration for an overall assessment of specific cell sources as manufacturing tools for therapeutic products, yet current scientific and regulatory positions focus, by design, on the safety and quality of such optimized cells [50,51]. Lawyers may help to interpret regulatory issues of organ donations and biological material use; biologists may select the appropriate cell source and process technical specifications; bioengineers may choose delivery and tissue engineering designs or preservation conditions; medical doctors may perform donor screening and informed consent documentation [31]. Specific aspects of the delivery vehicle and delivery route selection, cell dosing regimens, and the optimization of product effects may be inspired by previous studies around cutaneous tissue regeneration, yet specificities of the target lung tissues and related pulmonary affections require adaptations
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