PMID- 36330162
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221105
IS  - 2452-199X (Electronic)
IS  - 2452-199X (Linking)
VI  - 22
DP  - 2023 Apr
TI  - Fabricating 3-dimensional human brown adipose microtissues for transplantation 
      studies.
PG  - 518-534
LID - 10.1016/j.bioactmat.2022.10.022 [doi]
AB  - 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 mum. 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.
CI  - (c) 2022 The Authors.
FAU - Wang, Ou
AU  - Wang O
AD  - Department of Chemical and Biomolecular Engineering, University of 
      Nebraska-Lincoln, NE, USA.
AD  - Biomedical Engineering Program, University of Nebraska-Lincoln, NE, USA.
FAU - Han, Li
AU  - Han L
AD  - Department of Biomedical Engineering, Pennsylvania State University, PA, USA.
FAU - Lin, Haishuang
AU  - Lin H
AD  - Department of Chemical and Biomolecular Engineering, University of 
      Nebraska-Lincoln, NE, USA.
FAU - Tian, Mingmei
AU  - Tian M
AD  - China Novartis Institutes for BioMedical Research Co., Ltd., Beijing, China.
FAU - Zhang, Shuyang
AU  - Zhang S
AD  - Department of Chemistry, University of Nebraska-Lincoln, NE, USA.
FAU - Duan, Bin
AU  - Duan B
AD  - Mary & Dick Holland Regenerative Medicine Program and Division of Cardiology, 
      Department of Internal Medicine, University of Nebraska Medical Center, Omaha, 
      NE, USA.
FAU - Chung, Soonkyu
AU  - Chung S
AD  - Department of Nutrition, University of Massachusetts, Amherst, MA, USA.
FAU - Zhang, Chi
AU  - Zhang C
AD  - School of Biological Science, University of Nebraska-Lincoln, NE, USA.
FAU - Lian, Xiaojun
AU  - Lian X
AD  - Department of Biomedical Engineering, Pennsylvania State University, PA, USA.
FAU - Wang, Yong
AU  - Wang Y
AD  - Department of Biomedical Engineering, Pennsylvania State University, PA, USA.
FAU - Lei, Yuguo
AU  - Lei Y
AD  - Department of Chemical and Biomolecular Engineering, University of 
      Nebraska-Lincoln, NE, USA.
AD  - Department of Biomedical Engineering, Pennsylvania State University, PA, USA.
AD  - Huck Institutes of the Life Sciences, Pennsylvania State University, PA, USA.
LA  - eng
PT  - Journal Article
DEP - 20221027
PL  - China
TA  - Bioact Mater
JT  - Bioactive materials
JID - 101685294
PMC - PMC9619153
OTO - NOTNLM
OT  - Brown adipocyte
OT  - Microtissue
OT  - Obesity
OT  - Transplantation
OT  - Type 2 diabetes
COIS- Authors have no competing financial interests.
EDAT- 2022/11/05 06:00
MHDA- 2022/11/05 06:01
PMCR- 2022/10/27
CRDT- 2022/11/04 02:28
PHST- 2022/02/15 00:00 [received]
PHST- 2022/10/06 00:00 [revised]
PHST- 2022/10/18 00:00 [accepted]
PHST- 2022/11/04 02:28 [entrez]
PHST- 2022/11/05 06:00 [pubmed]
PHST- 2022/11/05 06:01 [medline]
PHST- 2022/10/27 00:00 [pmc-release]
AID - S2452-199X(22)00446-7 [pii]
AID - 10.1016/j.bioactmat.2022.10.022 [doi]
PST - epublish
SO  - Bioact Mater. 2022 Oct 27;22:518-534. doi: 10.1016/j.bioactmat.2022.10.022. 
      eCollection 2023 Apr.