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Table 1 3D Adipose Models of Obesity, Type II Diabetes Mellitus and Cancer

From: In vitro tissue-engineered adipose constructs for modeling disease

PublicationOrganismSource of Cells and Disease ContextScaffoldAdvantages over 2D / Major Findings
Emont et al. 2015
[119]
M. musculusInguinal
Fat Depot,
Perigonadal Fat Depot, SVF
Obesity
Collagen Hydrogel↑Expression:
Adipoq
Fabp4
Pparg
Distinct expression patterns between inguinal and perigonadal fat depots
Davidenko et al. 2010
[120]
M. Musculus3 T3-L1 s
(pre-adipocytes)
Obesity
Freeze Dried
Collagen-Hyaluronic Acid Crosslinked with EDC and NHS
↑ 3 T3-L1 Proliferation
adipsin
↑ Compressive Strength and Stiffness
Turner et al. 2014
[121]
M. Musculus3 T3-L1 s
Obesity
Copolymer of elastin-like polypeptide (ELP) and polyethyleneimine (PEI) to promote spheroid formation↑ Intracellular TG Content
↑ CD36
↑ CD40
↑ Pparg
↑ Adipoq
When Exposed to TNFα:
↑ Glycerol Secretion
↑ FFA Concentration in Media
Vidyasekar et al. 2016
[122]
M. MusculusBM-MSCsPLA microbeads polymerized with gelatin, alginate, dextran and pectin↑ Lipid Content (Nile Red)
↑ Expression:
Pparg
Fabp4
Cebpα
Perfusion Increased above parameters
Kuss et al. 2018
[123]
H. sapienshTERT immortalized isolates of BAT from a female patient
Obesity/T2DM
Photocrosslinkable Hyaluronic Acid and GelatinTunable Mechanical Properties
↑ Expression:
UCP1
PGC1A
ZIC1
↓ Expression:
HDAC1
↑ Max and Basal Respiration
↓ IL-6
Improved Glucose Uptake +/− Insulin
Hsiao et al. 2016
[124]
H. sapiensASCs
Obesity
collagen and fibrinogen encapsulated within an alginate cylindrical shellUnilocular Adipocytes
↑ Expression:
ADIPOQ
Mauney et al. 2007
[125]
H. sapiensASCs
hMSCs
Obesity
Silk↑ Expression:
FABP4
PPARγ
GLUT4
ADIPSIN
ACS
↑ Lipid Content (Oil Red O)
Implantable within Mice
Bellas et al. 2013
[126]
H. sapiensASCs
Obesity
SilkBuilt on system in Mauney et al.
Dynamic Spinning
Increased Culture Time to 6 months
Abbott et al. 2015
[127]
H. sapiensASCs derived from inguinal adipose tissue
Obesity
Silk in a PDMS microfluidics device3D + Perfusion:
↑ TGs
↑ Glycerol Secretion
↓ LDH
Aubin et al. 2015
[128]
H.
sapiens
ASCs
Microvascular endothelial cells
Obesity
Serum and Ascorbic Acid Stimulated
Self-assembled Cell Sheets
Long-term culture
Expressed similar to AT explant:
Leptin
ANGPT1
PAI-1
VEGF
HGF
Mature endothelial structures
Aubin et al. 2015
[129]
H.
sapiens
ASCs
Obesity
Serum and Ascorbic Acid Stimulated
Self-assembled Cell Sheets
Exposure to TNF-α:
↑ MCP-1
SLC2A4
FASN
↑ NF-κB-related transcripts
Dynamic culture increased lipid content
Qi et al. 2018
[130]
H. sapienshTERT immortalized isolates of WAT from a female patient
and
HUVECs
Obesity
methyacrylated HA, gelatin and PEG-4A-based hydrogel↑ Expression:
PPARG
LPL
CEBPB
Supports co-culture with endothelial cells
Daquinag et al. 2013
[131]
M. MusculusASCs from the SVF
3 T3-L1 s
bEND.3 Endothelial Cells
Magnetically Levitated CellsAbility to form spheroids
Decorin Deposition
Choi et al. 2010
[132]
H. sapiensASCs
HUVECs
Obesity/ T2DM
SilkIn co-culture w/ HUVECs and in high insulin:
↓ Intracellular TG Content
Abbott et al. 2016
[133]
H.
sapiens
Liquified Lipoaspirates:
Adipocytes,
ASCs,
fibroblasts,
smooth muscle pericytes
and endothelial cells
Obesity
Silk↑ Glycerol Secretion
↑ TG Secretion
When Exposed to TNFα:
↑ IL1-α
↑ OPG
↑ TIMP2
↑ IL-6
↑ IL-8
↑ RANTES
Das et al. 2015
[134]
H.
sapiens
Adipocytes derived from human nasal inferior turbinate tissue-derived mesenchymal stromal cells
Obesity
Silk-gelatin crosslinked with tyrosinase (bioink)PPARG
CEBPα
LPL
Proulx et al. 2016
[135]
H. sapiensASCs
Microvascular endothelial cells
Obesity
Serum and Ascorbic Acid Stimulated
Self-assembled Cell Sheets
Upon adipocytes
stimulated with TNF-α and IL-β:
↓ EC Length
↓ EC Branching
Proulx et al. 2018
[136]
H.
sapiens
M. musculus
hASCs
human microvascular endothelial cells grafted into nude mice
Obesity
Serum and Ascorbic Acid Stimulated
Self-assembled Cell Sheets
Integrated with host vasculature within 3 days
No significant loss of adipocyte volume after 14 days of implantation.
Yang et al. 2015
[137]*
H.
sapiens
ASCs
MCF-7 s
Cancer
Microfluidics deviceReal-time monitoring of tissue progression, Circulation-like dynamic flow of media, Studying the relationship between light penetration and tissue depth in photodynamic therapy
Dunn et al. 2014
[138]*
H. sapiensDecellularized subcutaneous adipose tissue from patients
Cancer
Human adipose tissue derived extracellular matrixModels ECM of Breast Cancer Tumor Microenvironment
Campbell et al. 2014
[139]
M. MusculusKIM-2
3 T3-L1 s
Cancer
Collagen/HARecapitulated mammary gland involution
Hume et al. 2018 (a)
[140]
H.
sapiens
MSCs
(isolated from mammoplasty surgery)
MDA-MB-231
Cancer
Collagen IAllowed:
7 days of co-culture of adipocytes and MDA-MB-231 cells
Multiphoton Microscopy
Determination of adipocyte-dependent contributions to MDA-MB-231 migration
Hume et al. 2018 (b)
[141]
H.
sapiens
3 T3-L1 s
MMTV-Wnt1 transgenic mouse (FVB background)
TUBO
(derived from Balb/c-Her2/neu transgenic
mouse)
Cancer
Collagen IAssess tumor fragment migration
↑ imaging capabilities due to optical clearing
MMTV-Wnt1
ROCK inhibitors promoted
MMTV-Wnt1 migration
72 h Adipocyte co-culture was anti-migratory in MMTV-Wnt1
Bougaret et al. 2018
[142]
H.
sapiens
ASCs
MCF-7
Cancer
Collagen-glycosaminoglycan-chitosanMCF-7 cells less sensitive to the effects of tamoxifen when co-cultured with adipocytes from obese women
May be due to difference in IL-6, leptin and TNFα
Mosaad et al. 2018
[143]
H.
sapiens
Adipocytes derived from
BM-MSCs
C42Bs
Cancer
Scaffold Free
PDMS microwell-mesh
↓ of C42B cell migration in co-culture with adipocytes
Lack of docetaxel resistance in C42B cells co-cultured with adipocytes
Herroon et al. 2016
[144]
M. musculus
H. sapiens
Mouse Adipocytes and macrophages derived from BM-MSCs
PC3s
Cancer
Spheroids grown on Collagen IVAdipocytes increased spheroid after 3 and 5 days of co-culture
Fairfield et al. 2018
[4]
M. Musculus
H. sapiens
Mouse and Human adipocytes derived from BM-MSCs
5TGM1
(Mouse Myeloma)
MM1S
(Human Myeloma)
OPM2
(Human Myeloma)
Cancer
SilkIn Adipocytes,
Upregulated transcripts
associated with:
Proliferation
Differentiation
Growth Factor Response
ECM Secretion
Pattern Specification
In Adipocytes,
Downregulated Transcripts associated with:
TLR-signaling
COX/COX2 Pathways
Lipoproteins
  1. References used in the publication that pertain to 3D adipose models of obesity, type II diabetes mellitus and cancer are presented here with details regarding: organism(s) used in the study, the specific cell types and disease context, the scaffold type and major findings. Studies highlighted with an asterisk (*) do not use differentiated adipocytes. Abbreviations: 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC), 4arm polyethylene glycol (PEG-4A), adiponectin (ADIPOQ), adipose-derived stem cells (ASCs), Angiopoietin-1 (ANGPT1), bone marrow-derived mesenchymal stem cells (BM-MSCs), Brown adipose tissue (BAT), CCAAT enhancer binding protein alpha or beta (CEBPα or β), cyclooxygenase (COX), elastin-like polypeptide (ELP), extra cellular matrix (ECM), fatty acid binding protein 4 (FABP4), hepatocyte growth factor (HGF), high-density lipoproteins (HDLs), hyaluronic acid (HA), interleukin 1α (IL-1α), interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), lactate dehydrogenase (LDH), lipoprotein lipase (LPL), monocyte chemoattractant protein-1 (MCP-1), mouse mammary tumor virus (MMTV), N-hydroxysuccinimide (NHS), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Osteoprotegerin (OPG), peroxisome proliferator-activated receptor gamma (PPAR-γ / Pparg), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1A), plasminogen activator inhibitor-1 (PAI-1), polydimethylsiloxane (PDMS), poly-lactic acid (PLA), regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), rho associated coiled-coil containing protein kinase (ROCK), stromal vascular fraction (SVF), three-dimensional (3D), toll-like receptors (TLR), Triacylglycerols (TGs), tumor necrosis factor alpha (TNF-α), two-dimensional (2D), type 2 diabetes mellitus (T2DM), uncoupling protein 1 (UCP1), vascular endothelial growth factor (VEGF), white adipose tissue (WAT)