Small Molecules for Organoid Culture

Organoids are 3D tissue culture models that allow for the study of organs in vitro. Derived from pluripotent stem cells, extracellular matrix and other supporting co-culture cells, and with the right culture conditions, organoids can form different cell types found in organs. The cells can organize into a similar structure as the tissue of origin and function similarly to the organ type being modeled.  

Small molecules are an essential tool for organoid culture due to their ease of use, controlled production methods and quality. R&D Systems portfolio provides a comprehensive selection of small molecules for the growth and maintenance of organoid and 3D tissue culture.  

Benefits of Using Small Molecules

Small molecules have several qualities that make them useful tools in the growth and maintenance of organoids: 

  • Ease of use: cell-permeability permits simple probe delivery 
  • Repeatable: exceptional quality ensures consistent results  
  • Good value: cost effective compared to viral vectors and antibody kits 
  • Tunable: concentration-dependent effects 
  • High quality: low lot-to-lot variability and high purity >98% 
  • Temporal control: rapid removal via media exchange 
CEPT Cocktail Kit

• Easy to use cell culture supplement for self-renewing pluripotent stem cells and their differentiated lineages

• Improves overall survival of cells for routine long-term passage, cryopreservation, single cell cloning and organoid formation

CEPT Cocktail Kit Img

Small Molecules for Organoid and 3D Cell Culture

Product Catalog #  Functions 
A 83-01* 2939 Selective inhibitor of TGF-βRI, ALK4/ALK7 
AGN 193109* 5758 High affinity pan-RAR antagonist 
AM 580* 0760 RARα agonist 
L-Ascorbic acid* 4055 Cav3.2 channels inhibitor 
N-Acetylcysteine7874Commonly used in multiple stages of organoid generation
BDNF (human) 2837 Activated TrkB and p75 neurotrophin receptors 
CEPT Cocktail Kit7991Cell culture supplement for improving stem cell survival containing Chroman 1, Emricasan, Polyamine Supplement, trans-ISRIB and DMSO 
CHIR 99021** 4423 Selective GSK-3 inhibitor, Wnt activator 
CHIR 99021 in solution 8170 Ready-to-use 10mM solution of CHIR 99021 pre-dissolved in DMSO  
Compound E 6476 γ-secretase and Notch pathway inhibitor  
DAPT* 2634 γ-secretase inhibitor 
DBZ* 4489 γ-secretase aspartyl protease inhibitor 
Dexamethasone* 1126 Anti-inflammatory glucocorticoid 
DMSO, Cell Cryopreserve Grade7726 Protective agent for freezing of cell cultures 
Dorsomorphin 3093 AMPK and BMP type 1 receptor inhibitor  
endo-IWR 1* 3532 Wnt/β-catenin signaling inhibitor 
Erlotinib Hydrochloride 7194 EGFR tyrosine kinase inhibitor 
Forskolin* 1099 Adenylyl cyclase activator 
Galunisertib 6956 ALK4/ALK5 (TGFβRI) inhibitor  
Gastrin I (human) 3006 Selective CCK2 agonist 
Heparin sodium salt 2812 Anticoagulant 
Hepes3173Multipurpose HEPES buffer; used in 3D cell culture
Iressa 3000 Selective EGFR inhibitor 
ISX 9* 4439 Neurogenic agent 
IWP 2 3533 Wnt pathway & PORCN inhibitor 
IWP 4 5214 Wnt/β-catenin signaling inhibitor 
LDN 193189** 6053 Selective ALK2/ALK3, Smad1/5/8 inhibitor 
LDN 193189 in solution 8150 Ready-to-use 10mM solution of LDN 193189 pre-dissolved in water  
Nicotinamide* 4106 PARP-1 inhibitor 
PD 0325901 4192 MEK1/2 inhibitor 
PD 0332991 4786 Cdk4/6 inhibitor 
Prostaglandin E2 2296 Promotes hematopoietic stem cell expansion 
RepSox* 3742 TGF-βRI inhibitor 
Retinoic Acid* 0695 Retinoic acid receptor agonist  
Rosiglitazone 5325 Selective PPARγ agonist 
RS 2462048853R-Spondin-1 substitute used to initiate small intestinal organoids
SANT-1 1974 Hedgehog pathway inhibitor 
SB 202190 1264 Selective p38 MAPK inhibitor 
SB 431542** 1614 Selective TGF-βRI, ALK4/ALK7 inhibitor 
Staurosporine* 1285 Non-selective protein kinase inhibitor 
T3* 6666 Thyroid hormone 
Thiazovivin3845ROCK inhibitor; improves the efficiency of fibroblast reprogramming and induction of iPSCs
TM2 TEAD inhibitor 7917 TEAD-mediated Hippo/Yap signaling inhibitor  
Tocriscreen Stem Cell Library 7340 A library of 120 stem cell compounds to explore stem cell reprogramming, differentiation, proliferation and signaling 
XAV 939** 3748 Tankyrase inhibitor 
WIKI4 4855 Tankyrase inhibitor 
Wnt-C59 5148 PORCN inhibitor 
Y-27632 1248Selective ROCK inhibitor; inhibits ROCK1 (p160 ROCK) and ROCK2; stem cell freezing (cryopreservation) media component
Y-27632 in solution7000Sterile-filtered 10 mM solution of Y-27632, selective ROCK inhibitor, pre-dissolved in water

*Ancillary Material Grade Small Molecules and **GMP small molecules are available 

Fluorescent Dyes for Organoids and 3D Cell Culture

R&D Systems brand offers a wide range of fluorescent dyes for organoid and 3D cell culture, enabling to visualize cellular structures, track dynamic cellular processes, assess various functional parameters, and perform high-content imaging and phenotypic analysis with compatibility for advanced microscopy and imaging platforms.

Wash-free Imaging of Extracellular Matrix in Live Tissues

With Rhobo6 ECM Dye, a cell-impermeable glycan-binding fluorophore

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Organoid Data Using Small Molecules

Culture and Characterization of iPSC-derived Human Intestinal Organoids. 

iPSC-derived human intestinal organoids were cultured using Y-27632 dihydrochloride (Catalog # 1254), SB 202190 (p38 MAPK Inhibitor) (Catalog # 1264), N-Acetylcysteine (Catalog # 7874), A 83-01 (Catalog # 2939), Nicotinamide (Catalog # 4106), along with the other reagents listed in the human intestinal organoid culture protocol. (A) Human intestinal organoids were stained using a Human/Mouse/Rat Vimentin Antibody (Catalog # MAB2105; green) and a Human/Mouse Desmin Antibody (Catalog # AF3844; red) to visualize myofibroblast cells and counterstained with DAPI (Catalog # 5748; blue). (B) Human intestinal organoids were stained using Human/Mouse E-Cadherin Antibody (Catalog # AF748; green) and a MUC2 Antibody (Catalog # NBP2-44431; red) and counterstained with DAPI (Catalog # 5748; blue).

Culture and Characterization of iPSC-derived Human Intestinal Organoids
Brain Organoid Img

Culture and Characterization of iPSC-derived Cerebral Organoids. 

iPSC-derived cerebral organoids (day 45) were cultured using Cultrex UltiMatrix RGF Basement Membrane Extract (Catalog # BME001-05) and brain organoid culture medium, which includes Y-27632 dihydrochloride (Catalog #1254), along with other reagents listed in the brain organoid culture recipe. Cerebral organoids were stained for Syto6 (blue), Pax6 (red), and Vimentin (green). (A) Image taken at 4x magnification. (B) An enlarged view of the area shown within the white box in part A of the figure. (C) Image taken at 15x magnification. Images courtesy of LifeCanvas Technologies.

Additional Resources

The Organoid Handbook

This handbook highlights some of the notable publications that have used organoids to investigate questions about development, disease, or drug safety. Additionally, it includes recipes and links to the key reagents that our own in-house scientists have used to establish the culture conditions for different types of organoids.

Small Molecules for Stem Cell Research Guide

Stem cells possess the unique abilities of self-renewal and differentiation, making them a crucial resource in medical research and regenerative therapies. This brochure serves as a guide to the application of small molecules in stem cell research, covering their roles in reprogramming, self-renewal, differentiation, organoid generation, and regenerative medicine.

Organoid Protocols

These protocols offer a guide to culturing organoids for various organs (intestines, lung, liver, and more), including equipment, R&D Systems reagents, steps for culturing organoids and resources to relevant published protocols.