CINXE.COM

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hreflang="x-default" /> <link href="https://www.tocris.com/resources/tocris-blog/five-reasons-use-small-molecules-stem-cell-research" rel="alternate" hreflang="en" /> <link href="https://www.tocris.com/cn/resources/tocris-blog/%E5%9C%A8%E5%B9%B2%E7%BB%86%E8%83%9E%E7%A0%94%E7%A9%B6%E4%B8%AD%E4%BD%BF%E7%94%A8%E5%B0%8F%E5%88%86%E5%AD%90%E7%9A%84%E4%BA%94%E4%B8%AA%E7%90%86%E7%94%B1" rel="alternate" hreflang="zh-cn" /> <meta name="baidu-site-verification" content="bMqlqGgPRi" /> <title>Small Molecules for Stem Cell Research | Blog | Tocris Bioscience</title> <meta name="description" content="This article outlines five reasons why you should be using small molecules in stem cell research" /> <script id="json-ld" type="application/ld+json">[{"@context":"https://schema.org/","@type":"Blog","name":"Small Molecules for Stem Cell Research | Blog","description":"This article outlines five reasons why you should be using small molecules in stem cell research","dateCreated":"2018/02/15","url":"https://www.tocris.com/resources/tocris-blog/five-reasons-use-small-molecules-stem-cell-research","keywords":"","text":"\r\n\r\nStem cells are defined by their ability to differentiate into specialized cells and to self-renew. Pluripotent stem cells (PSCs), of which embryonic stem cells (ESCs) are an example, can differentiate into almost all cell types within the body. Somatic, or adult, cells such as fibroblasts can also be reprogrammed to generate induced pluripotent stem cells (iPSCS).\r\n\r\nTypically, reprogramming of somatic cells and differentiation of PSCs into terminal lineages was achieved through exogenous gene expression, via retroviral transfer. This method is inefficient, with production of a relatively small number of cells taking weeks. Additionally, viral vectors must be carefully selected and tested as they have the potential to introduce genetic material or mutations into the cell genome and to be tumorigenic.\r\n\r\nUsing small molecules for reprogramming and differentiation, as well as maintenance and proliferation of cells in culture has advantages over these methods.\r\n\r\n\r\n\r\nSmall molecules are cost effective, quick and convenient\r\n\r\nCompared to exogenous gene expression methods, small molecules have effects within hours and greatly reduce the time associated with reprogramming and differentiation. For example, a small molecule cocktail, including SB 431542 (Cat.No. 1614), LDN 193189 (Cat.No. 6053), XAV 939 (Cat.No. 3748), PD 0325901 (Cat.No. 4192), SU 5402 (Cat.No. 3300) and DAPT (Cat.No. 2634) has been shown to differentiate iPSCs into functional cortical neurons within 16 days (Qi et al, 2017).\r\n\r\nSmall molecules are synthetically produced\r\n\r\nSmall molecules are chemically produced, in contrast to proteins such as growth factors, which are manufactured via biological means. Small molecules therefore have a high level of purity and low batch to batch variation, ensuring consistent activity and reproducible results when used in stem cell culture.\r\n\r\nSmall molecules are cell permeable and tuneable\r\n\r\nSmall molecules are cell permeable, so can be used to target intracellular signaling pathways in both in vitro cell culture and in vivo. They also have concentration-dependent actions and can therefore be used in multiple protocols with different outcomes. For example, CHIR 99021 (Cat.No. 4432) can be used at 20 \u00b5M to transdifferentiate fibroblasts into neurons (Li et al, 2015) and at 3 \u00b5M to maintain a population of murine ESCs (Kolodziejczyk et al, 2015).\r\n\r\nSmall molecules have good temporal control\r\n\r\nGiven their rapid and reversible effects, small molecules can target a protein (or multiple proteins) with high temporal control. This is particularly important in protocols where the effects of a small molecule are required for a specific time period.\r\n\r\nSmall molecules are safe\r\n\r\nExogenous gene expression using viral vectors has the potential to introduce unwanted genetic material, but animal-free small molecules are devoid of this possibility. Considering the therapeutic potential of iPSC-derived cell therapies, the safety of small molecule use is very important.\r\n\r\nReferences\r\n\r\nKolodziejczyk et al. (2015) Single cell RNA-sequencing of pluripotent states unlocks modular transcription variation. Cell Stem Cell. 17, 471. PMID: 26431182\r\n\r\nLi et al. (2015) Small-molecule driven direct reprogramming of mouse fibroblasts into functional neurons. Cell Stem Cell. 17, 195. PMID: 26253201\r\n\r\nQi et al. (2017) Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells. Nat. Biotechnol. 35, 154. PMID: 28112759\r\n"},{"@context":"http://schema.org","@type":"WebPage","breadcrumb":{"@context":"http://schema.org","@type":"BreadcrumbList","itemListElement":[{"@context":"http://schema.org","@type":"ListItem","position":1,"item":{"@context":"http://schema.org","@type":"Thing","@id":"https://www.tocris.com/","name":"Home"}},{"@context":"http://schema.org","@type":"ListItem","position":2,"item":{"@context":"http://schema.org","@type":"Thing","@id":"https://www.tocris.com/resources","name":"Resources"}},{"@context":"http://schema.org","@type":"ListItem","position":3,"item":{"@context":"http://schema.org","@type":"Thing","@id":"https://www.tocris.com/resources/tocris-blog","name":"Tocris Blog"}}]},"potentialaction":{"query":""}}]</script> <meta name="generator" content="Drupal 7 (https://www.drupal.org)" /> <link rel="shortlink" href="https://www.tocris.com/node/986" /> <meta property="og:site_name" content="Tocris Bioscience" /> <meta property="og:type" content="article" /> <meta 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2018 </time> <div> <div class="region region-content"> <section id="block-system-main" class="block block-system clearfix"> <div> <div class="field field-name-body field-type-text-with-summary field-label-hidden"><div class="field-items"><div class="field-item even" property="content:encoded"><div class="blog-image-border"><img alt="Small Molecules for Stem Cell Research" itemprop="image" src="https://resources.tocris.com/images/blog/banners/small-molecules-stem-cell-research.jpg?v=2" title="Five reasons to use Small Molecules in Stem Cell Research" /></div> <p><a href="/cell-biology/stem-cells" target="_blank">Stem cells</a> are defined by their ability to differentiate into specialized cells and to self-renew. Pluripotent stem cells (PSCs), of which embryonic stem cells (ESCs) are an example, can differentiate into almost all cell types within the body. Somatic, or adult, cells such as fibroblasts can also be reprogrammed to generate induced pluripotent stem cells (iPSCS).</p> <p>Typically, <a href="/cell-biology/stem-cell-reprogramming" target="_blank">reprogramming</a> of somatic cells and <a href="/cell-biology/stem-cell-differentiation" target="_blank">differentiation</a> of PSCs into terminal lineages was achieved through exogenous gene expression, via retroviral transfer. This method is inefficient, with production of a relatively small number of cells taking weeks. Additionally, viral vectors must be carefully selected and tested as they have the potential to introduce genetic material or mutations into the cell genome and to be tumorigenic.</p> <p>Using small molecules for reprogramming and differentiation, as well as maintenance and <a href="/cell-biology/stem-cell-proliferation" target="_blank">proliferation</a> of cells in culture has advantages over these methods.</p> <p><img alt="Small Molecules for Stem Cell Research" itemprop="image" src="https://resources.tocris.com/images/blog/why-use-small-molecules-circle-850x500.png" title="Five reasons to use Small Molecules in Stem Cell Research" /></p> <h2>Small molecules are cost effective, quick and convenient</h2> <p>Compared to exogenous gene expression methods, small molecules have effects within hours and greatly reduce the time associated with reprogramming and differentiation. For example, a small molecule cocktail, including <a href="/products/sb-431542_1614" target="_blank">SB 431542</a>聽(Cat.No. 1614),聽<a href="/products/ldn-193189-dihydrochloride_6053" target="_blank">LDN 193189</a>聽(Cat.No. 6053), <a href="/products/xav-939_3748" target="_blank">XAV 939</a>聽(Cat.No. 3748), <a href="/products/pd-0325901_4192" target="_blank">PD 0325901</a>聽(Cat.No. 4192), <a href="/products/su-5402_3300" target="_blank">SU 5402</a>聽(Cat.No. 3300) and <a href="/products/dapt_2634" target="_blank">DAPT</a>聽(Cat.No. 2634)聽has been shown to differentiate iPSCs into functional cortical neurons within 16 days (Qi <em>et al</em>, 2017).</p> <h2>Small molecules are synthetically produced</h2> <p>Small molecules are chemically produced, in contrast to proteins such as growth factors, which are manufactured via biological means. Small molecules therefore have a high level of purity and low batch to batch variation, ensuring consistent activity and reproducible results when used in stem cell culture.</p> <h2>Small molecules are cell permeable and tuneable</h2> <p>Small molecules are cell permeable, so can be used to target intracellular signaling pathways in both <em>in vitro</em> cell culture and <em>in vivo</em>. They also have concentration-dependent actions and can therefore be used in multiple protocols with different outcomes. For example, <a href="/products/chir-99021_4423" target="_blank">CHIR 99021</a>聽(Cat.No. 4432) can be used at 20 碌M to transdifferentiate fibroblasts into neurons (Li <em>et al</em>, 2015) and at 3 碌M to maintain a population of murine ESCs (Kolodziejczyk <em>et al</em>, 2015).</p> <h2>Small molecules have good temporal control</h2> <p>Given their rapid and reversible effects, small molecules can target a protein (or multiple proteins) with high temporal control. This is particularly important in protocols where the effects of a small molecule are required for a specific time period.</p> <h2>Small molecules are safe</h2> <p>Exogenous gene expression using viral vectors has the potential to introduce unwanted genetic material, but animal-free small molecules are devoid of this possibility. Considering the therapeutic potential of iPSC-derived cell therapies, the safety of small molecule use is very important.</p> <p><strong>References</strong></p> <p>Kolodziejczyk <em>et al</em>. (2015) <a href="https://www.ncbi.nlm.nih.gov/pubmed/26431182" rel="nofollow" target="_blank">Single cell RNA-sequencing of pluripotent states unlocks modular transcription variation</a>. Cell Stem Cell. <strong>17</strong>, 471. PMID: 26431182</p> <p>Li <em>et al</em>. (2015) <a href="https://www.ncbi.nlm.nih.gov/pubmed/26253201" rel="nofollow" target="_blank">Small-molecule driven direct reprogramming of mouse fibroblasts into functional neurons</a>. Cell Stem Cell. <strong>17</strong>, 195. PMID: 26253201</p> <p>Qi <em>et al.</em> (2017) <a href="https://www.ncbi.nlm.nih.gov/pubmed/28112759" rel="nofollow">Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells</a>. Nat. Biotechnol.聽<strong>35</strong>, 154. PMID:聽28112759</p> </div></div></div><div class="field field-name-field-blog-categories field-type-taxonomy-term-reference field-label-above"><div class="field-label">Blog Categories: </div><div class="field-items"><div class="field-item even"><a href="/resources/tocris-blog/blog-categories/stem-cells" typeof="skos:Concept" property="rdfs:label skos:prefLabel">Stem Cells</a></div><div class="field-item odd"><a href="/resources/tocris-blog/blog-categories/small-molecules" typeof="skos:Concept" property="rdfs:label skos:prefLabel">Small Molecules</a></div></div></div><div class="field field-name-field-tags field-type-taxonomy-term-reference field-label-above"><div class="field-label">Tags: </div><div class="field-items"><div class="field-item even"><a href="/resources/tocris-blog/tags/stem-cells" typeof="skos:Concept" property="rdfs:label skos:prefLabel">Stem Cells</a></div><div class="field-item odd"><a href="/resources/tocris-blog/tags/small-molecules" typeof="skos:Concept" 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