A study published in Engineering has introduced a new method to produce functional organoids directly from human adult adipose tissue. This approach eliminates the need for isolating stem cells or employing genetic manipulation, providing a simpler and more scalable process for organoid generation. The research, carried out by scientists from the Shanghai Jiao Tong University School of Medicine and the Shanghai Institute for Plastic and Reconstructive Surgery, demonstrates that human adipose tissue can naturally give rise to organoids representing all three germ layers—mesoderm, endoderm, and ectoderm—through a specialized suspension culture system.
By using a specialized suspension culture system, the team developed reaggregated microfat (RMF) tissues that could be guided to form organoids with diverse functions. One major outcome of the study was the successful creation of humanized bone marrow organoids from RMF tissues. When these RMF structures were implanted in immunodeficient mice, they underwent endochondral ossification, forming ossicles that contained both endosteal and perivascular niches. These ossicles supported the engraftment and differentiation of human hematopoietic stem cells, effectively replicating the structural and functional characteristics of human bone marrow. The findings suggest that such organoids can provide a reliable model for studying human hematopoiesis in vivo.
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The research team also demonstrated the ability of RMF tissues to differentiate into insulin-producing islet organoids. Following a four-stage differentiation process, RMF cells progressed through definitive endoderm, pancreatic progenitor, endocrine progenitor, and β-cell stages. The resulting organoids secreted insulin in response to glucose and exhibited a marked increase in secretion under high-glucose conditions. When transplanted into diabetic mice, the islet organoids became vascularized and successfully normalized blood glucose levels, maintaining glucose control throughout the study period.
Further experiments revealed the ectodermal differentiation potential of RMF tissues. Under neural induction conditions, RMF pellets formed neurospheres that subsequently differentiated into neuronal and glial lineages. These cells expressed molecular markers characteristic of neural stem cells, mature neurons, and glial cells, confirming the conversion of adipose-derived RMF tissues into functional neural-like structures.
Overall, the study demonstrates the versatility of adult adipose tissue as a practical and clinically relevant source of organoids. By simplifying the process and forgoing stem cell isolation, the RMF-based method reduces technical barriers while maintaining functional fidelity.