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Regenerative Medicine Related Reagents

The term regenerative medicine refers to a next-generational field of medical techniques in which cells are taken from patients, cultured, expanded, and returned to the patient in some manner in order to regenerate tissues or promote wound healing. The vast majority of these techniques, including cell sheet engineering – using patient-derived cell sheets to promote wound healing, and decellularized whole-organ engineering – the generation of intact organs using a decellularized scaffold along with the patient’s own cells, involve the use of stem cells with the same genotype as the original patient. Not only does this allow for the avoidance of transplant rejection, but it is also widely expected to help overcome the worldwide organ shortage.

The type of stem cell perhaps most frequently employed in these applications are known as induced pluripotent stem cells (iPSCs). iPSCS were developed by Professor Shinya Yamanaka at Kyoto University in a landmark paper in 2006.1) Professor Yamanaka was able to return fibroblasts to an undifferentiated state and confer upon them the same regenerative potential as embryonic stem cells through the induction of a combination of four transcription factors – Oct3/4, Sox2, Klf4, and c-Myc. He also demonstrated how these cells could be coerced down different lineages through the application of appropriately timed signaling factors.


Reprogamming methods used in the production of iPS cells

Reprogamming methods used in the production of iPS cells


In recent years, organoids have come to the forefront as a model for the application of human iPSCs in regenerative medicine. Organoids are in-vitro 3D cultured cell aggregates derivable from both iPSCs as well as somatic stem cells which are not only capable of self-organization and long term self-renewal, but which also exhibit similar morphology and function to the tissues from which they were derived.2) This is achieved through the use of physical and biochemical cues, such as extracellular matrix components and niche factors, which are able to recapitulate cells' natural environment within living tissue.


Organoid culture pipeline

Organoid culture pipeline


Here at TCI, we have an extensive lineup of chemicals frequently used in both organoid culture and iPS generation / differentiation. Find below a table containing common medium additives used to generate tissue-specific organoids from both hSSCs and hiPSC, as well as several lists of common inhibitors and activators, organized by signaling pathway.



Tissue Type Origin Culture Conditions Reference
Small Intestine hAdSCs A83-01, Nicotinamide, N-Acetylcysteine, Y-27623, SB202190, EGF, Rspondin1, Noggin, Wnt-3a 3
hPSCs EGF, Rspondin1, FGF-4, Noggin, Wnt-3a, Activin A 4
Large Intestine hAdSCs A83-01, Nicotinamide, N-Acetylcysteine, Y-27623, SB202190, EGF, Rspondin1, Noggin, Wnt-3a 3
Stomach hAdSCs A83-01, Nicotinamide, N-Acetylcysteine, Y-27623, EGF, Rspondin, FGF-10, Gastrin, Noggin, Wnt-3a 5
hPSCs CHIR 99021, Y-27623, Retinoic Acid, EGF, FGF-4, BMP-4, Noggin, Activin A, Wnt-3a 6
Lung hAdSCs A83-01, Nicotinamide, Y-27632, SB202190, Rspondin1, FGF-7, FGF-10, Noggin 7
hPSCs [for Differentiation]
SB431542, SANT-2, SU-5402, bFGF, Noggin, SHH, SAG, Activin A

[for Organoid Culture]
CHIR 99021, SB431542, FGF-4, Noggin
8
Brain hPSCs Y-27632, Heparin, 2-Mercaptoethanol, bFGF, Insulin 9
Liver hAdSCs [for Organoid Culture]
Y-27632, A83-01, Nicotinamide, N-Acetylcysteine, Forskolin, EGF, Rspondin1, FGF-10, Gastrin, Noggin, Wnt-3a, HGF

[for Hepatocyte Differentiation]
A83-01, DAPT, Dexamethasone, EGF, FGF-19, BMP-7, Gastrin, HGF
10
hPCSs bFGF, BMP-4, Activin A, HGF, Oncostatin M 11
Pancreas hAdSCs A83-01, Nicotinamide, N-Acetylcysteine, EGF, Rspondin1, FGF-10, Gastrin, Noggin, Wnt-3a 12
Kidney hPCs [for Differentiation]
CHIR 99021, 2-Mercaptoethanol, Heparin, Retinoic Acid, 1-Thioglycerol, bFGF, FGF-9, BMP-2, BMP-4, Insulin, Activin A, Holo-transferrin

[for Organoid Culture]
CHIR 99021, Heparin, FGF-9, HGF, GDNF
13, 14
Prostate hAdSCs Y-27623, A83-01, Nicotinamide, N-Acetylcysteine, SB202190, Prostaglandin E2, Testosterone, EGF, Rspondin1, FGF-10, bFGF, Noggin 15
hPCs [for Differentiation]
FGF-10, Activin A, Wnt-10b

[for Organoid Culture]
Retinoic Acid, Testosterone, EGF, Rspondin1, Noggin
16

References

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Growth Factors

Characterized as cytokines, growth factors are the name for soluble proteins that initiate signaling cascades in cells related to proliferation, differentiation, survival, inflammation, and tissue repair.


Chemical Name Target Effect
rhEGF EGFR Ligand/Agonist
rhFGF2 FGFR Ligand/Agonist

Products

R0262
rhEGF (Human, Recombinant)
R0263
rhFGF2 (Human, Recombinant)

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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Prostaglandin Signaling Pathway

Prostaglandins, a metabolic derivative of arachidonic acid, play key roles in vasodilation and the generation of the inflammatory response.


Chemical Name Target Effect
Prostaglandin E1 EP1–4 Ligand/Agonist
Prostaglandin E2 EP1–4 Ligand/Agonist

Products

P1917
Prostaglandin E1
P1884
Prostaglandin E2

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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MAPK Signaling Pathways

The mammalian MAPK (Mitogen-Activated Protein Kinase) signaling pathways transmit a wide variety of signals from outside the cell through the activation of MAPKs, and are divided into three subgroups based on the specific MAPK at work: ERK, JNK, or p38.

ERK1/2 Signaling Pathway

The ERK/MAPK signaling pathway, playing major roles in cell proliferation and differentiation, begins via extracellular signals received at membrane-embedded receptor proteins such as receptor tyrosine kinases, integrins, and ion channels. Different combinations of ligand/receptor result in the activation of slightly different downstream effectors, but in general, signals from the receptor first reach an adaptor protein such as Shc, GRB2, or Crk, which is then transmitted via activation of a guanine nucleotide exchange factor such as SOS or C3G. This in turn allows for the activation of GTP binding proteins such as Ras and Rap1, which phosphorylate and activate the MAPKKK (MAPK Kinase Kinase) Raf, which phosphorylates and activates the MAPKK (MAPK Kinase) MEK1/2, which finally phosphorylates and activates ERK. Activated ERK dimer is then able to phosphorylate and activate downstream molecules not only in the cytoplasm but also in the nucleus.


ERK1/2 Signaling Pathway


p38 Signaling Pathway

As one of the three principal MAPK signaling pathways in mammals, the p38 MAPK signaling pathway plays a similar role as the JNK signaling pathway as a mediator of the cell’s response to environmental and genetic stress. In mammals, four isoforms exist (the p38α, p38β, p38γ, and p38δ isoforms), with p38α/β as the main isoforms. Upon direct and indirect activation via Akt, TNFα, Wip1, etc., p38α/β is able to phosphorylate and activate various targets in both the cytoplasm and nucleus, the most prominent of which being p53, MSK1/2, and HBP1. p38α/β activation also results in the downregulation of certain effector molecules such as Cdc25B and CycD1, highlighting the role that p38 plays in the cell cycle.

JNK Signaling Pathway

As one of the three principal MAPK signaling pathways in mammals, the JNK MAPK signaling pathway plays a similar role as the p38 signaling pathway as a mediator of the cell’s response to environmental and genetic stress. Upon direct and indirect activation via Akt, Tak1, TNFα, ROS, etc., JNK is able to phosphorylate and activate various targets in both the cytoplasm and nucleus, the most prominent of which being p53, PPARγ, HSP1, c-Jun, and Stat3. JNK activation also results in the downregulation of certain effector molecules such as Bcl2 and Bim, highlighting the role that JNK plays in determination of cell fate.

JNK Signaling Pathway


Chemical Name Target Effect
GW-5074 c-Raf Inhibitor
Sorafenib c-Raf, B-Raf Inhibitor
PD 98059 MEK1/2, AHR Inhibitor
SL 327 MEK1/2 Inhibitor
PD 184352 MEK1/2 Inhibitor
SP 600125 JNK1/2/3, Aurora A, FLT3, TRKA Inhibitor
SU 3327 JNK Inhibitor
SB 239063 p38α/β Inhibitor
SB 203580 p38 Inhibitor
FR 180204 ERK1/2 Inhibitor
Honokiol ERK1/2, Akt ERK1/2: Activator, Akt: Inhibitor
PD 169316 p38 Inhibitor
VX-702 p38α Inhibitor

Products

G0609
GW-5074
O0599
Sorafenib
A2529
PD 98059
L0331
SL 327
P2174
PD 184352
A2548
SP 600125
A2940
SU 3327
B5898
SB 239063
F0864
SB 203580
F1214
FR 180204
H1309
Honokiol
P2532
PD 169316
V0147
VX-702

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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PI3K/Akt Signaling Pathway

PI3K mediates conversion of PIP2 to PIP3 on the inner leaflet of the cell membrane upon recruitment to the membrane following activation of various receptor proteins including integrin, RTKs, cytokine receptors, B-cell receptors, and GPCRs. PIP3 acts as binding sites for various factors such as PDK1 and mTORC2, as well as Akt, which is activated via phosphorylation by PDK1 and mTORC2. Akt (Protein Kinase B) is a protein kinase which has as target proteins mTORC1, MDM2, Bad, CDK2, Lamin A, IKKα, FOXO1, P27, and GSK-3, among others, giving it an important role in the regulation of such cellular processes as cell growth, survival, motility, metabolism, and protein synthesis.


PI3K/Akt Signaling Pathway


Chemical Name Target Effect
LY 294002 PI3K Inhibitor
Miltefosine PI3K Inhibitor
3-Methyladenine PI3K Inhibitor
Quercetin PI3K Inhibitor
Wortmannin PI3K Inhibitor

Products

M2410
LY 294002
M2445
Miltefosine
M2518
3-Methyladenine
P0042
Quercetin Hydrate
W0007
Wortmannin

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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PKC Signaling Pathway

Protein Kinase C (PKC) is a family of serine/threonine-kinases divided into three subfamilies based on which associated factors (Ca2+, DAG) are required for their phosphorylation-mediated activation.


Chemical Name Target Effect
Bisindolylmaleimide I PKC Inhibitor
Fasudil PKC, etc. Inhibitor
Staurosporine PKC, etc. Inhibitor

Products

B5781
Bisindolylmaleimide I
F0839
Fasudil Hydrochloride
T4000
Staurosporine

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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Wnt Signaling Pathway

The Wnt signaling pathway can be divided into the canonical and non-canonical (planar cell polarity and Wnt-calcium) pathways. In the canonical pathway, the Wnt receptor (a dimer of Fz and LRP5/6) sequesters the β-catenin destruction complex upon ligand binding, allowing the build-up of β-catenin in the nucleus. Once in the nucleus, β-catenin complexes with Tcf/Lef transcription factors to control the expression of various downstream genes. The canonical pathway plays major roles in the determination of cell fate during embryonic development, including the determination of body axis, and contributes to the regulation of differentiation and maintenance of stemness.


Wnt Signaling Pathway (OFF)
Wnt Signaling Pathway (ON)

Chemical Name Target Effect
CHIR 99021 GSK-3α/β Inhibitor
IWP-2 CK1δ Inhibitor
IWR-1 Tankyrase Inhibitor

Products

C2943
CHIR 99021
F0839
IWP-2
I1167
IWR-1

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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Cadherin Signaling Pathway

The cadherin family of genes play critical roles in calcium-dependent cell-cell contact and adhesion, in part mediating contact inhibition and epithelial-to-mesenchymal transition. The canonical cadherins are E-cadherin, N-cadherin, and P-cadherin, which associate with catenins to activate the Wnt, NFκB, Hippo, and RhoA signaling pathways.


Chemical Name Target Effect
DAPT γ-Secretase Inhibitor

Products

D4257
DAPT

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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Notch Signaling Pathway

The notch pathway is highly conserved among multicellular organisms due to its roles in cell-fate determination during early development as a mediator of cell/cell contact. Nascient notch receptor is transported to the cell membrane, where binding with such ligands as Jagged and DII cause it to be cleaved in turn by the ADAM family proteases and the γ-secretase complex. This results in liberation of notch’s intracellular domain (Notch-ICD), which is transported to the nucleus to act as a transcription factor upon complexing with CSL and MAML.


Notch Signaling Pathway


Products

D4257
DAPT

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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Hedgehog Signaling Pathway

The Hedgehog (Hh) signaling pathway was first discovered due to the essential role it plays in body plan determination during development, but it has also been shown to be important for maintaining stem cell-ness in somatic stem cells. The mammalian Hedgehog ligands comprise three homologues (Desert – DHH, Indian – IHH, Sonic – SHH) with SHH being the most well studied. SHH binding to the Patched-1 (PTCH1) receptor abrogates PTCH1's repressive effect on Smoothened (SMO), which can then activate members of the GLI family of transcription factors, which go on to promote transcription of downstream factors.


Hedgehog Signaling Pathway


Products

J0009
Jervine

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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TGFβ Signaling Pathway

The receptors for the TGFβ signaling pathway are single-pass serine/threonine cell surface receptors, and are divided into two groups, type 1 and type 2 receptors. These receptors form a covalent disulfide bond with a receptor of the other type, forming a dimer which then itself dimerizes into a tetramer. The extracellular ligands this tetramer binds to, as well as the affinity and sensitivity of each subunit towards these ligands is used to separate the TGFβ family into three major groups, the TGFβ, BMP (Bone Morphogenic Protein), and Activin subgroups. Upon binding to a ligand, such proteins as Smad2/3, Smad1/5/8, and/or Tak1 are phosphorylated and activated, leading to an increase in the expression of genes related to embryonic development, cell proliferation and apoptosis. The TGFβ pathway is often dysregulated in cancer, and its inhibition is commonly required in organoid culture.


TGFβ Signaling Pathway


Products

A3324
A83-01
B4003
SB 431542
B5776
SB-525334
B6056
SB-505124
I1110
SIS 3 Hydrochloride
R0224
RepSox

‡Our reagents are not explicitly guaranteed for cell culture. Please filter sterilize etc. before use.

References

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