Organoid

Organoids refer to miniature tissue structures that self-assemble from stem cells under three-dimensional in vitro culture conditions and can partially recapitulate the cellular composition and spatial arrangement of real organs.

Organoids lack a vascular system, which leads to easy necrosis in the central region, limited size and insufficient maturity, and consistency between batches is poor.

The limitations of organoids and organ-on-a-chip include: a single organ chip can hardly reflect interactions among multiple organs, and the stability of long-term culture, batch-to-batch consistency, and the degree of standardization remain bottlenecks.

The advantage of organoids and organ-on-a-chip over animal models lies in their human origin—they directly use human cells, avoiding extrapolation errors caused by species differences.

A key reason for the functional immaturity of organoids is believed to be an incomplete communication environment: in natural tissues, multiple cell types coordinate with one another through complex paracrine and contact-dependent signaling, whereas laboratory culture systems usually contain only a few cell types and limited growth factors.

Organoids refer to three-dimensional micro-tissues formed by the self-organization of stem cells in the laboratory, capable of partially simulating the structure and function of real organs; at present, most organoids are still significantly inferior to natural tissues in function—for example, cultured cardiac organoids have insufficient contractile force and immature electrophysiological properties, and cultured liver organoids have low expression levels of metabolic enzymes.

The challenges facing Intero include: ensuring consistency across different batches of organoids, reducing production costs to a level acceptable to pharmaceutical companies, and persuading regulators to recognize the validity of organoid data in applications.

Replacing animal testing is an irreversible direction, but the specific technical routes are still competing, with organoids, organ-on-a-chip, and AI-driven computational toxicology each having their own adherents.

The advantage of organoids lies in their authentic cell sources and ability to reflect complex human biological characteristics; the shortcoming lies in the lack of systemic environments such as the immune system and blood circulation.

Currently, organoids and organ-on-a-chip are regarded as complementary rather than mutually exclusive alternatives to animal testing.

Over the past decade, academia has accumulated a large amount of organoid research in fields such as oncology, liver, and kidney.

The FDA Modernization Act 2.0 does not ban animal testing, but rather allows pharmaceutical companies, with FDA recognition, to use human-cell-based alternative methods (such as organoids, organ-on-a-chip, and computer models) to meet safety assessment requirements.

Truly turning organoids into standardized, scalable commercial products that can be delivered remains an engineering challenge.

In vitro organoids lack a vascular system, causing internal cells to die from insufficient oxygen and nutrient supply; they also lack immune cell regulation and cannot form complete sensory input and motor output circuits.

The 2022 FDA Modernization Act 2.0 was passed by the U.S. Congress and eliminated the mandatory requirement for animal testing in new drug approvals.