A recent study published in Engineering has revealed a new approach to generate functional organoids from adult human adipose tissue. This method, which bypasses traditional stem cell isolation and genetic manipulation, offers a simpler and more scalable route to creating organoids that can be used in regenerative medicine and disease modeling.
The research, led by a team from Shanghai Jiao Tong University School of Medicine and the Shanghai Institute of 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. Using a specialized suspension culture system, the team developed reconstituted microfatty (RMF) tissues that could differentiate into various functional organelles.
One of the key findings of the study is the production 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 beads, when implanted in mice, underwent endochondral ossification, forming ossicles that contained both endostenic and perivascular niches. These osteocytes supported engraftment and differentiation of human hematopoietic stem cells, demonstrating their potential as a model for the study of human hematopoiesis.
In addition to bone marrow organoids, the study also investigated the differentiation of RMF tissues into insulin-producing islet organoids. Using a sophisticated four-step protocol, the researchers guided RMF cells through definitive endodermal, pancreatic progenitor, endocrine progenitor, and β-cell stages. The resulting islet organoids were able to secrete 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 revascularized and reversed hyperglycemia, maintaining normal blood glucose levels during the study.
The researchers also demonstrated the potential for extradermal differentiation of RMF tissues to create neuron-like tissues. RMF pellets were induced to form neurospheres, which then differentiated into neuronal and glial lineages. The cells expressed markers for neural stem cells, mature neurons, and glial cells, indicating successful conversion of adipose tissue to neural tissue.
This study highlights the versatility and potential of adult human adipose tissue as a source for organoid production. By avoiding complex cell isolation and genetic manipulation, the RMF-based strategy offers a more practical and clinically relevant approach to generate 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 blood disorders.
The research highlights the importance of exploring alternative sources for organoid production, especially those that can be easily accessed and processed. As the field of regenerative medicine continues to advance, the ability to create functional organoids from readily available tissues such as adipose tissue could pave the way for more effective and accessible treatments.
