A recent study published in Engineering has unveiled a novel approach to generating functional organoids from human adult adipose tissue. This method, which bypasses traditional stem cell isolation and genetic manipulation, offers a more straightforward and scalable pathway for creating organoids that can be used in regenerative medicine and disease modeling.

The research, led by a team from the Shanghai Jiao Tong University School of Medicine and the Shanghai Institute for Plastic and Reconstructive Surgery, demonstrates the potential of human adult adipose tissue to differentiate into organoids representing all three germ layers—mesoderm, endoderm, and ectoderm—without the need for single-cell processing. By employing a specialized suspension culture system, the team developed reaggregated microfat (RMF) tissues that could differentiate into various functional organoids.

One of the key findings of the study is the generation of humanized bone marrow organoids from RMF tissues. These organoids were able to support human hematopoiesis in immunodeficient mice, mimicking the structural and functional complexity of native human bone marrow. The researchers found that RMF pellets, when implanted into mice, underwent endochondral ossification, forming ossicles that contained both endosteal and perivascular niches. These ossicles supported the engraftment and differentiation of human hematopoietic stem cells, demonstrating their potential as a model for studying human hematopoiesis.

In addition to bone marrow organoids, the study also explored the differentiation of RMF tissues into insulin-producing islet organoids. Using a refined four-stage protocol, the researchers guided RMF cells through definitive endoderm, pancreatic progenitor, endocrine progenitor, and β-cell stages. The resulting islet organoids were capable of secreting insulin in response to glucose stimulation, with a significant increase in insulin secretion under high-glucose conditions. When transplanted into diabetic mice, these organoids rapidly vascularized and reversed hyperglycemia, maintaining normal blood glucose levels for the duration of the study.

The researchers also demonstrated the ectodermal differentiation potential of RMF tissues by generating neural-like tissues. RMF pellets were induced to form neurospheres, which then differentiated into neuronal and neuroglial lineages. The cells expressed markers for neural stem cells, mature neurons, and glial cells, indicating the successful conversion of adipose tissue into neural-like tissues.

This study highlights the versatility and potential of human adult adipose tissue as a source for organoid generation. By avoiding complex cell isolation and genetic manipulation, the RMF-based strategy offers a more practical and clinically relevant approach to creating functional organoids. The findings suggest that adipose tissue could serve as a valuable resource for developing therapeutic applications in regenerative medicine, particularly for conditions such as diabetes and hematological disorders.

The research underscores the importance of exploring alternative sources for organoid generation, especially those that can be easily accessed and processed. As the field of regenerative medicine continues to advance, the ability to generate functional organoids from readily available tissues like adipose tissue could pave the way for more efficient and accessible treatments.

The paper “Direct Differentiation of Human Adult Adipose Tissue into Multilineage Functional Organoids,” is authored by Ru-Lin Huang, Jing Yang, Yuxin Yan, Xiangqi Liu, Xiya Yin, Chuanqi Liu, Xingran Liu, Rehanguli Aimaier, Qiumei Ji, Gen Li, Tao Zan, Kang Zhang, Qingfeng Li. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.06.031. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.