Fabricating 3-dimensional human brown adipose microtissues for transplantation studies
Transplanting cell cultured brown adipocytes (BAs) represents a promising approach to prevent and treat obesity (OB) and its associated metabolic disorders, including type 2 diabetes mellitus (T2DM). However, transplanted BAs have a very low survival rate in vivo. The enzymatic dissociation during t...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-04-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22004467 |
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| author | Ou Wang Li Han Haishuang Lin Mingmei Tian Shuyang Zhang Bin Duan Soonkyu Chung Chi Zhang Xiaojun Lian Yong Wang Yuguo Lei |
| author_facet | Ou Wang Li Han Haishuang Lin Mingmei Tian Shuyang Zhang Bin Duan Soonkyu Chung Chi Zhang Xiaojun Lian Yong Wang Yuguo Lei |
| author_sort | Ou Wang |
| collection | DOAJ |
| description | Transplanting cell cultured brown adipocytes (BAs) represents a promising approach to prevent and treat obesity (OB) and its associated metabolic disorders, including type 2 diabetes mellitus (T2DM). However, transplanted BAs have a very low survival rate in vivo. The enzymatic dissociation during the harvest of fully differentiated BAs also loses significant cells. There is a critical need for novel methods that can avoid cell death during cell preparation, transplantation, and in vivo. Here, we reported that preparing BAs as injectable microtissues could overcome the problem. We found that 3D culture promoted BA differentiation and UCP-1 expression, and the optimal initial cell aggregate size was 100 μm. The microtissues could be produced at large scales via 3D suspension assisted with a PEG hydrogel and could be cryopreserved. Fabricated microtissues could survive in vivo for long term. They alleviated body weight and fat gain and improved glucose tolerance and insulin sensitivity in high-fat diet (HFD)-induced OB and T2DM mice. Transplanted microtissues impacted multiple organs, secreted protein factors, and influenced the secretion of endogenous adipokines. To our best knowledge, this is the first report on fabricating human BA microtissues and showing their safety and efficacy in T2DM mice. The proposal of transplanting fabricated BA microtissues, the microtissue fabrication method, and the demonstration of efficacy in T2DM mice are all new. Our results show that engineered 3D human BA microtissues have considerable advantages in product scalability, storage, purity, safety, dosage, survival, and efficacy. |
| first_indexed | 2024-04-10T20:56:25Z |
| format | Article |
| id | doaj.art-29cb852fcd1a4bad96d4998509e74f76 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:34:14Z |
| publishDate | 2023-04-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-29cb852fcd1a4bad96d4998509e74f762024-04-16T17:41:26ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-04-0122518534Fabricating 3-dimensional human brown adipose microtissues for transplantation studiesOu Wang0Li Han1Haishuang Lin2Mingmei Tian3Shuyang Zhang4Bin Duan5Soonkyu Chung6Chi Zhang7Xiaojun Lian8Yong Wang9Yuguo Lei10Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, NE, USA; Biomedical Engineering Program, University of Nebraska-Lincoln, NE, USADepartment of Biomedical Engineering, Pennsylvania State University, PA, USADepartment of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, NE, USAChina Novartis Institutes for BioMedical Research Co., Ltd., Beijing, ChinaDepartment of Chemistry, University of Nebraska-Lincoln, NE, USAMary & Dick Holland Regenerative Medicine Program and Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USADepartment of Nutrition, University of Massachusetts, Amherst, MA, USASchool of Biological Science, University of Nebraska-Lincoln, NE, USADepartment of Biomedical Engineering, Pennsylvania State University, PA, USADepartment of Biomedical Engineering, Pennsylvania State University, PA, USADepartment of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, NE, USA; Department of Biomedical Engineering, Pennsylvania State University, PA, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, PA, USA; Corresponding author. The Pennsylvania State University, PA, USA.Transplanting cell cultured brown adipocytes (BAs) represents a promising approach to prevent and treat obesity (OB) and its associated metabolic disorders, including type 2 diabetes mellitus (T2DM). However, transplanted BAs have a very low survival rate in vivo. The enzymatic dissociation during the harvest of fully differentiated BAs also loses significant cells. There is a critical need for novel methods that can avoid cell death during cell preparation, transplantation, and in vivo. Here, we reported that preparing BAs as injectable microtissues could overcome the problem. We found that 3D culture promoted BA differentiation and UCP-1 expression, and the optimal initial cell aggregate size was 100 μm. The microtissues could be produced at large scales via 3D suspension assisted with a PEG hydrogel and could be cryopreserved. Fabricated microtissues could survive in vivo for long term. They alleviated body weight and fat gain and improved glucose tolerance and insulin sensitivity in high-fat diet (HFD)-induced OB and T2DM mice. Transplanted microtissues impacted multiple organs, secreted protein factors, and influenced the secretion of endogenous adipokines. To our best knowledge, this is the first report on fabricating human BA microtissues and showing their safety and efficacy in T2DM mice. The proposal of transplanting fabricated BA microtissues, the microtissue fabrication method, and the demonstration of efficacy in T2DM mice are all new. Our results show that engineered 3D human BA microtissues have considerable advantages in product scalability, storage, purity, safety, dosage, survival, and efficacy.http://www.sciencedirect.com/science/article/pii/S2452199X22004467Brown adipocyteMicrotissueTransplantationObesityType 2 diabetes |
| spellingShingle | Ou Wang Li Han Haishuang Lin Mingmei Tian Shuyang Zhang Bin Duan Soonkyu Chung Chi Zhang Xiaojun Lian Yong Wang Yuguo Lei Fabricating 3-dimensional human brown adipose microtissues for transplantation studies Bioactive Materials Brown adipocyte Microtissue Transplantation Obesity Type 2 diabetes |
| title | Fabricating 3-dimensional human brown adipose microtissues for transplantation studies |
| title_full | Fabricating 3-dimensional human brown adipose microtissues for transplantation studies |
| title_fullStr | Fabricating 3-dimensional human brown adipose microtissues for transplantation studies |
| title_full_unstemmed | Fabricating 3-dimensional human brown adipose microtissues for transplantation studies |
| title_short | Fabricating 3-dimensional human brown adipose microtissues for transplantation studies |
| title_sort | fabricating 3 dimensional human brown adipose microtissues for transplantation studies |
| topic | Brown adipocyte Microtissue Transplantation Obesity Type 2 diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X22004467 |
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