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medium. This medium can effectively reduce the risk of evaluation. At present, no strict and universally binding
batch variation, ensure the reproducibility of the culture operational and quality control standards have been
system, and successfully realize the process of culturing established globally to standardize the organoid culture
iPSCs into liver organoids. process. The absence of such a standardized system will

The culture protocol of organoids also suffers from inevitably introduce additional variables into organoid-
great inter-laboratory variation, with significant differences related research, thereby affecting the reliability and
in the induction protocols (type of growth factors, comparability of research results. At present, only a
concentration, time of addition, etc.) used by different limited number of guidelines for organoid quality control
researchers during cell culture. This technical operation, have been published. ISSCR has released the “Standards
which is highly dependent on the operator’s personal for Human Stem Cell Use in Research,” standardizing
experience, leads to poor experimental reproducibility. This processes such as the sourcing of hPSCs/hASCs, ethical
ultimately results in inconsistent organoid differentiation approval, and cell identity verification. The European
results, creating obvious inter-batch differences. The Committee for Standardization and the European
key to addressing batch-to-batch variability in organoid Committee for Electrotechnical Standardization, among
culture processes is the use of high-throughput technology. other organizations, have jointly published the “Roadmap
High-throughput technology encompasses automated for Organ-on-Chip Standardization,” comprehensively
sample processing, microfluidics, OoC systems, and high- deploying OoC standardization efforts and accelerating the
content imaging techniques. By leveraging these high- standardization process for OoC. The Organoid Standards
throughput technologies, researchers can efficiently and Initiative released the “Organoid Manufacturing and
rapidly complete the culture and analysis steps in organoid Application Guidelines” in 2024, systematically outlining the
research, ensuring consistency and reproducibility across complete process from organoid preparation to application,
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experiments. Schuster et al. developed a standardized, to establish global unified standards for organoid culture,
miniaturized, and automated high-throughput microfluidic validation, and application. Although various institutions
platform. This platform enables the cultivation of organoids have introduced standards and specifications applicable
or 3D cell cultures in a reliable environment with minimal to their operations, a consensus on organoid standards
reagent consumption and reproducible conditions, while remains unavailable internationally.
simultaneously monitoring and screening cell phenotypes. 5.3. Challenges facing clinical translation
This allows researchers to obtain a large amount of reliable
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experimental data at a lower cost. Li et al. also developed Although technological breakthroughs in MSK organoids
a high-throughput polymethyl methacrylate microfluidic are emerging in cutting-edge fields, their translation
chip that can be used to study the growth of tumor spheroids into preclinical and clinical applications is accompanied
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under different combinations of factor concentrations and by serious and complex obstacles. The first challenge
to perform combined drug screening on tumor spheroids. arises from the research starting point: cell source and
These studies have demonstrated the importance of high- informed consent. Organoid culture is highly dependent
throughput technology in organoid research, effectively on biological samples from human donors. During the
addressing the shortcomings of traditional research process of collecting samples, many volunteers who donate
methods. samples often find it difficult to understand the cutting-
edge concept of organoids and the complex application
In addition to the lack of uniform standards in the scenarios that their cells may undergo in the future.
culture process, the characterization system of organoids This dilemma is exacerbated by the prevalence of broad
also faces the dilemma of insufficient standardization. At consent. Donors, especially those seeking treatment
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present, there is a lack of clear and quantifiable evaluation for MSK injuries or illnesses, may be unaware that their
standards for the key parameters of organoids, such as the samples will ultimately be used to construct organoid
degree of mineralization of bone organoids, the spatial models, which may in turn be involved in drug screening
distribution characteristics of proteoglycans in cartilage chains, biomaterials development, and even grafts. It is even
organoids, and the arrangement pattern of myotubes in more challenging to anticipate the enormous commercial
muscle organoids, all of which lack a unified evaluation value that their samples may generate. This information
system. Meanwhile, the expression profiles of key functional asymmetry and ambiguity in informed consent constitute
genes and proteins in MSK organoids at the molecular level a significant contradiction in the current development
have not yet been established as standardized databases. of organoids, which seriously undermine the rights and
These standardization deficiencies have hindered the interests of donors. A traceable and updatable electronic
practical application of organoids. consent system should be established for new scenarios,
Overall, there is a lack of a standardized system for key such as organoids, drug development, and commercial
aspects, such as cell acquisition, culture, and functional transformation, where samples may be used in the future,

Volume 1 Issue 3 (2025) 21 doi: 10.36922/OR025280024