Li Qingfeng Team from Shanghai Ninth People's Hospital Achieves World's First Cross-Germ Layer Adipose Regeneration

Background

Regenerative medicine has long pursued methods to generate functional tissues for treating diseases such as diabetes, blood disorders, and neurological conditions. Conventional approaches to creating organoids typically involve digesting tissues into single cells, extensive in vitro expansion, genetic reprogramming to induce pluripotency, and subsequent differentiation and reaggregation. These steps can introduce genomic instability, increase tumorigenic risks, and raise concerns about immune rejection in the case of allogeneic cells.

The Department of Plastic and Reconstructive Surgery at Shanghai Ninth People's Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, has conducted research leveraging adipose tissue, which is readily available and frequently used in reconstructive procedures. Professor Li Qingfeng leads the team, which includes Professor Ru-Lin Huang. On October 27, 2025, media reports detailed the team's publication in the journal Engineering.

What was achieved

The Li Qingfeng team published the paper titled "Direct Differentiation of Human Adult Adipose Tissue into Multilineage Functional Organoids" in Engineering. This work is reported as achieving the world's first direct cross-germ layer reprogramming of human adult adipose tissue into functional organoids representing all three embryonic germ layers without single-cell dissociation, genetic modification, or passage through a pluripotent state.

The researchers generated mesodermal bone marrow organoids capable of reconstituting human normal hematopoiesis in immunodeficient mice, endodermal insulin-producing islet-like organoids that reversed hyperglycemia in streptozotocin-induced diabetic mice, and ectodermal neural-like tissues with TUJ1+/GFAP+ positive rate greater than 85%. The islet-like organoids demonstrated glucose-responsive insulin secretion with a significant increase under high-glucose conditions. Long-term in vivo experiments showed no tumorigenicity. The team has initiated clinical translation research for diabetes treatment, supporting a shift toward a "tissue-to-new-tissue" reprogramming paradigm.

How it works

The technique starts with adult human adipose tissue obtained through minimally invasive means. This tissue undergoes mechanical emulsification to produce microfat fragments. These are then placed in a specialized suspension culture system, where they self-organize and reaggregate into stable pellets known as reaggregated microfat (RMF), with a typical diameter of 4 mm. This approach preserves the original tissue's cellular diversity, niches, and intercellular interactions without breaking it down to individual cells.

From the RMF pellets, specific chemical signals and staged culture conditions direct differentiation along chosen pathways. For islet-like organoids, a four-stage protocol guides the cells through definitive endoderm, pancreatic progenitor, endocrine progenitor, and beta-cell-like stages, resulting in structures capable of insulin production in response to glucose. Similar directed protocols produce neural-like tissues expressing neuronal and glial markers or bone marrow organoids that support blood cell formation in vivo. By avoiding cell isolation, prolonged expansion, genetic reprogramming, and pluripotent intermediates, the method aims to reduce associated safety risks while enabling autologous, personalized organoids.

What it means for international patients

The research demonstrates the potential of a patient's own adipose tissue as a scalable source for generating functional organoids across germ layers, which could support future regenerative therapies for conditions including diabetes, hematological disorders, and neural repair. As an autologous approach that bypasses certain risks of traditional stem cell methods, it may facilitate safer, personalized treatments. The team’s initiation of clinical translation research for diabetes indicates progress toward possible clinical applications.

Shanghai Ninth People's Hospital operates an International Medical Department, opened in January 2024 at its Pudong campus, offering one-stop services including English-speaking coordinators, professional interpreters, bilingual medical records, and partnerships with commercial insurance providers. It serves international patients seeking specialized care. Availability and eligibility for any applications of this emerging technology have not been detailed publicly and must be confirmed directly with the hospital, as it remains at the research and early translational stage.

About the hospital

Shanghai Ninth People's Hospital is a Grade 3A tertiary public hospital located in Shanghai and affiliated with Shanghai Jiao Tong University School of Medicine. It maintains campuses in the Huangpu and Pudong districts. The hospital is particularly known for its Department of Plastic and Reconstructive Surgery, where the Li Qingfeng team is based, as well as strengths in oral and maxillofacial surgery, dentistry, ophthalmology, and otolaryngology.

It has developed dedicated international patient services through its International Medical Department, which provides personalized, high-end care with multilingual support and direct billing arrangements with insurers. Professor Li Qingfeng serves in the plastic and reconstructive surgery department. The hospital functions as a major center for clinical care, education, and research in its specialty areas.