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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

Publication

Organism

Source of Cells and Disease Context

Scaffold

Advantages over 2D / Major Findings

Emont et al. 2015

[119]

M. musculus

Inguinal

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. Musculus

3 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. Musculus

3 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. Musculus

BM-MSCs

PLA 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. sapiens

hTERT immortalized isolates of BAT from a female patient

Obesity/T2DM

Photocrosslinkable Hyaluronic Acid and Gelatin

Tunable Mechanical Properties

↑ Expression:

UCP1

PGC1A

ZIC1

↓ Expression:

HDAC1

↑ Max and Basal Respiration

↓ IL-6

Improved Glucose Uptake +/− Insulin

Hsiao et al. 2016

[124]

H. sapiens

ASCs

Obesity

collagen and fibrinogen encapsulated within an alginate cylindrical shell

Unilocular Adipocytes

↑ Expression:

ADIPOQ

Mauney et al. 2007

[125]

H. sapiens

ASCs

hMSCs

Obesity

Silk

↑ Expression:

FABP4

PPARγ

GLUT4

ADIPSIN

ACS

↑ Lipid Content (Oil Red O)

Implantable within Mice

Bellas et al. 2013

[126]

H. sapiens

ASCs

Obesity

Silk

Built on system in Mauney et al.

Dynamic Spinning

Increased Culture Time to 6 months

Abbott et al. 2015

[127]

H. sapiens

ASCs derived from inguinal adipose tissue

Obesity

Silk in a PDMS microfluidics device

3D + 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. sapiens

hTERT 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. Musculus

ASCs from the SVF

3 T3-L1 s

bEND.3 Endothelial Cells

Magnetically Levitated Cells

Ability to form spheroids

Decorin Deposition

Choi et al. 2010

[132]

H. sapiens

ASCs

HUVECs

Obesity/ T2DM

Silk

In 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. sapiens

ASCs

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 device

Real-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. sapiens

Decellularized subcutaneous adipose tissue from patients

Cancer

Human adipose tissue derived extracellular matrix

Models ECM of Breast Cancer Tumor Microenvironment

Campbell et al. 2014

[139]

M. Musculus

KIM-2

3 T3-L1 s

Cancer

Collagen/HA

Recapitulated mammary gland involution

Hume et al. 2018 (a)

[140]

H.

sapiens

MSCs

(isolated from mammoplasty surgery)

MDA-MB-231

Cancer

Collagen I

Allowed:

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 I

Assess 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-chitosan

MCF-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 IV

Adipocytes 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

Silk

In 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)