Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significa...Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significant challenges in terms of safety and scalability for clinical applications.An alternative strategy involves the direct generation of organoids from readily available tissues.Herein,we report the generation of functional organoids representing all three germ layers from human adult adipose tissue without single-cell processing steps.Specifically,by employing a specialized suspension culture system,we have developed reaggregated microfat(RMF)tissues,which differentiated into mesodermal bone marrow organoids capable of reconstituting human normal hematopoiesis in immunodeficient mice,endodermal insulin-producing organoids that reversed hyperglycemia in streptozotocin(STZ)-induced diabetic mice,and ectodermal nervous-like tissues resembling neurons and neuroglial cells.These findings therefore highlight the potential of human adipose tissue as a safe,scalable,and clinically viable source for organoid-based regenerative therapies.展开更多
基金supported by the National Natural Science Foundation of China(82372535 to Ru-Lin Huang and 82361138568 to Qingfeng Li)the Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by Science and Technology Commission of Shanghai Municipality(22MC1940300)the Shanghai Plastic Surgery Research Center of Shanghai Priority Research Center(2023ZZ02023)。
文摘Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significant challenges in terms of safety and scalability for clinical applications.An alternative strategy involves the direct generation of organoids from readily available tissues.Herein,we report the generation of functional organoids representing all three germ layers from human adult adipose tissue without single-cell processing steps.Specifically,by employing a specialized suspension culture system,we have developed reaggregated microfat(RMF)tissues,which differentiated into mesodermal bone marrow organoids capable of reconstituting human normal hematopoiesis in immunodeficient mice,endodermal insulin-producing organoids that reversed hyperglycemia in streptozotocin(STZ)-induced diabetic mice,and ectodermal nervous-like tissues resembling neurons and neuroglial cells.These findings therefore highlight the potential of human adipose tissue as a safe,scalable,and clinically viable source for organoid-based regenerative therapies.
