Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control
Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equ...
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Published in | Molecular therapy Vol. 30; no. 1; pp. 341 - 354 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
05.01.2022
American Society of Gene & Cell Therapy |
Subjects | |
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Abstract | Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice. Specifically, by introducing a FRL-triggered optogenetic device into human mesenchymal stem cells (hMSCs), which we encapsulated in poly-(l-lysine)-alginate and implanted subcutaneously under the dorsum of T1D model mice, we achieved FRL illumination-inducible secretion of insulin that yielded improvements in glucose tolerance and sustained blood glucose control over traditional insulin glargine treatment. Moreover, the FAID cell implants attenuated both oxidative stress and development of multiple diabetes-related complications in kidneys. This optogenetics-controlled “living cell factory” platform could be harnessed to develop multiple synthetic designer therapeutic cells to achieve long-term yet precisely controllable drug delivery.
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Haifeng Ye and his colleagues described far-red light-responsive designer cells engineered for blood glucose control. They showed that implantation of these cells and daily illumination offers long-term control of blood glucose in diabetic mice. This optogenetic designer cell technology confers protection against both diabetes-associated oxidative stress and kidney damage. |
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AbstractList | Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice. Specifically, by introducing a FRL-triggered optogenetic device into human mesenchymal stem cells (hMSCs), which we encapsulated in poly-(l-lysine)-alginate and implanted subcutaneously under the dorsum of T1D model mice, we achieved FRL illumination-inducible secretion of insulin that yielded improvements in glucose tolerance and sustained blood glucose control over traditional insulin glargine treatment. Moreover, the FAID cell implants attenuated both oxidative stress and development of multiple diabetes-related complications in kidneys. This optogenetics-controlled "living cell factory" platform could be harnessed to develop multiple synthetic designer therapeutic cells to achieve long-term yet precisely controllable drug delivery. Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice. Specifically, by introducing a FRL-triggered optogenetic device into human mesenchymal stem cells (hMSCs), which we encapsulated in poly-( l -lysine)-alginate and implanted subcutaneously under the dorsum of T1D model mice, we achieved FRL illumination-inducible secretion of insulin that yielded improvements in glucose tolerance and sustained blood glucose control over traditional insulin glargine treatment. Moreover, the FAID cell implants attenuated both oxidative stress and development of multiple diabetes-related complications in kidneys. This optogenetics-controlled “living cell factory” platform could be harnessed to develop multiple synthetic designer therapeutic cells to achieve long-term yet precisely controllable drug delivery. Haifeng Ye and his colleagues described far-red light-responsive designer cells engineered for blood glucose control. They showed that implantation of these cells and daily illumination offers long-term control of blood glucose in diabetic mice. This optogenetic designer cell technology confers protection against both diabetes-associated oxidative stress and kidney damage. Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice. Specifically, by introducing a FRL-triggered optogenetic device into human mesenchymal stem cells (hMSCs), which we encapsulated in poly-(l-lysine)-alginate and implanted subcutaneously under the dorsum of T1D model mice, we achieved FRL illumination-inducible secretion of insulin that yielded improvements in glucose tolerance and sustained blood glucose control over traditional insulin glargine treatment. Moreover, the FAID cell implants attenuated both oxidative stress and development of multiple diabetes-related complications in kidneys. This optogenetics-controlled “living cell factory” platform could be harnessed to develop multiple synthetic designer therapeutic cells to achieve long-term yet precisely controllable drug delivery. [Display omitted] Haifeng Ye and his colleagues described far-red light-responsive designer cells engineered for blood glucose control. They showed that implantation of these cells and daily illumination offers long-term control of blood glucose in diabetic mice. This optogenetic designer cell technology confers protection against both diabetes-associated oxidative stress and kidney damage. |
Author | Zhou, Jian Gao, Ling Qiao, Longliang Zhang, Mingliang Zhou, Yang Yu, Guiling Ye, Haifeng Yin, Jianli Wang, Yiwen |
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Keywords | type 1 diabetes far-red light cell therapy optogenetics synthetic designer cell blood glucose control oxidative stress renal damage |
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SubjectTerms | Animals Blood Glucose blood glucose control cell therapy Diabetes Mellitus, Type 1 - therapy Diabetes Mellitus, Type 2 far-red light Humans Insulin - metabolism Insulin Secretion Mice optogenetics Original oxidative stress renal damage synthetic designer cell type 1 diabetes |
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Title | Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control |
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