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Cellular proliferation describes an increase in cell number caused by cell growth and division into two identical daughter cells. Production of cells identical to the parent is termed 'self-renewal.' Unlike other cell types, stem cells have the ability to replicate many times.
|Cat. No.||Product Name / Activity|
|Potent AMPK activator; inhibits MSC proliferation|
|Maintains self-renewal of human iPSCs; selective inhibitor of TGF-βRI, ALK4 and ALK7|
|Selectively eliminates NSCs in hESC-derived cell populations; also broad-spectrum ion channel blocker|
|7001||AT 7867 New|
|Induces proliferation of iPSC-derived pancreatic progenitor cells; pan-Akt and PKA inhibitor|
|Maintains self-renewal and pluripotency of ESCs; potent inhibitor of GSK-3; also inhibits cdks|
|AhR antagonist; promotes expansion of human hematopoietic stem cells|
|Highly potent and selective ROCK 2 inhibitor; improves cell survival after cryogeneisis|
|4027||16,16-Dimethyl Prostaglandin E2|
|Induces stem cell proliferation|
|Increases number of viable HSC during harvesting; DPP-IV inhibitor|
|Suppresses spontaneous differentiation of human ESCs; adenosine deaminase inhibitor|
|Negative control for ELA-32 (Cat.No.6291)|
|Apelin receptor agonist; promotes self-renewal and primes hESCs toward endoderm lineage|
|Converts epiblast stem cells to ESCs and promotes ESC self-renewal; CK1 inhibitor|
|Preserves stemness and promotes proliferation of undifferentiated cells; Frizzled 4 allosteric agonist|
|Antibiotic; activates short-term renewal of ESCs|
|Optimizes naïve human pluripotent stem cell growth and viability; PKC inhibitor|
|2910||H 89 dihydrochloride|
|Improves survival and clonogenicity of dissociated human ESCs; PKA inhibitor|
|E2F transcription factor inhibitor; attenuates hESC proliferation|
|Sustains self-renewal and pluripotency of ESCs|
|Dyrk1A/B inhibitor; impairs self-renewal of NSCs|
|Enables Wnt/β-catenin-driven expansion of ESCs; prevents spontaneous differentiation|
|Promotes survival of hPSCs in combination with other small molecules; also integrated stress response (ISR) inhibitor|
|PORCN inhibitor; suppresses self-renewal in R1 ESCs|
|Self-assembling peptide; forms hydrogel to support cell growth|
|1130||LY 294002 hydrochloride|
|Prototypical PI 3-kinase inhibitor; suppresses proliferation of mESCs|
|Promotes HSC expansion; also FBPase inhibitor|
|5779||NSC 23005 sodium|
|Potently promotes HSC expansion ; p18INK inhibitor|
|Promotes expansion of erythroid progenitors|
|Selective FGFR1 and -3 inhibitor; inhibits proliferation and differentiation of oligodendrocyte progenitors|
|MEK inhibitor; enhances ESC self-renewal|
|Acts synergistically with Y-27632 (Cat.No. 1254) to improve PSC cloning efficiency; PPARγ agonist|
|Dual ERK1/RasGAP inhibitor. Maintains ESC self-renewal|
|6991||Poly Vinyl Alcohol|
|Carrier molecule for stem cell culture; replaces serum albumin for ex vivo stem cell expansion|
|Induces hematopoietic stem cell proliferation|
|Enhances survival of human ESCs following enzymatic dissociation|
|Promotes stability of human PSCs; potent, selective inhibitor of p38 MAPK|
|Selective inhibitor of p38 MAPK; stimulates neural stem cell proliferation|
|GSK-3 inhibitor; maintains mouse ESCs in a pluripotent state|
|Induces proliferation, differentiation and sheet formation of ESC-derived endothelial cells|
|Used for maintaining stem cells in naive pluripotent state; selective JNK inhibitor|
|Supports mESC self-renewal; potent FGFR and VEGFR inhibitor|
|Maintains pluripotency of hESCs; heparin sulfate antagonist|
|High affinity 15-PGDH inhibitor; promotes hematopoiesis and hepatocyte proliferation|
|Improves survival of hESCs; ROCK inhibitor|
|Selective PPARγ agonist; inhibits growth of hematopoietic cell lines|
|Regulates hPSCs self-renewal; also potent, selective inhibitor of MEK1 and 2|
|Supports self-renewal of naive hESCs|
|Selective ROCK inhibitor; increases survival rate of human embryonic stem cells undergoing cryopreservation|
|Promotes survival of muscle stem cells (MuSCs); MDM2 inhibitor; activates p53 activity|
|Enhances the self-renewal capability of NSCs; notch signaling pathway activator; active in vivo|
Proliferation and self-renewal of stem cells occurs via the division of a cell into two identical daughter cells, resulting in the production of cells identical to the parent. Unlike other cell types, such as muscle or blood cells, stem cells are able to replicate many times. Under the right conditions stem cells can continue to proliferate in culture over many months without differentiation and specialization, yielding millions of cells; this is known as long-term self-renewal.
The proliferation and maintenance of stem cells in the undifferentiated pluripotent state is controlled by signaling pathways, growth factors and transcription factors. Three transcription factors, Oct4, Sox2 and Nanog, are key to maintaining pluripotency and self-renewal. The transcription factors enhance the activity of genes associated with maintaining the pluripotent state, while repressing genes that enable stem cell differentiation. The expression of Oct4, Sox2 and Nanog is controlled by the LIF, Wnt and TGF-β/BMP signaling pathways, respectively, and activation of all three pathways in associated with the maintenance of stem cells in the pluripotent state. A change in the expression of one of the three core transcription factors switches the stem cell from self-renewal to differentiation.
The ability of stem cells to proliferate is beneficial for regenerative medicine. Signaling pathway inhibitor compounds have been found to maintain proliferation and pluripotency of stem cells in long term culture and offer the advantage for medicinal use of being chemically-defined. A combination of the GSK-3 inhibitor CHIR 99021 with the MEK inhibitor PD 0325901, for example (known as 2i), can maintain long-term self-renewal of embryonic stem cells (ESCs). Conventional stem cell culture techniques require mouse embryonic fibroblast (MEF) 'feeder' cells, serum products and growth factors, which have the potential to introduce unwanted animal pathogens into stem cell culture.
Although 2i containing medium can be used to maintain stem cell self-renewal almost indefinitely, stem cells are susceptible to apoptosis upon routine passage. Rho-kinase (ROCK) inhibitors, such as Y-27632, have been shown to significantly reduce apoptosis of ESCs during passage.
Pathologically, the excessive proliferation of cancer stem cells can lead to the formation of tumors.
Tocris offers the following scientific literature for Stem Cell Proliferation to showcase our products. We invite you to request* your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.
Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.