Stem cell therapies are the leading and most sensational topic in the world of scientific research. The excitement is due to the huge potential these cells have in curing human diseases.
What are stem cells? They are undifferentiated cells in human body that are capable of differentiating into specialized cell types.
Stem cells differentiate into different cell types during early life and growth. In many tissues, they provide an internal repair system and also divide to replenish other cells.
These cells can remain as stem cells or undergo division to develop into specialized cells such as muscle cell, red blood cells, or brain cells. Two specialized features that sets them apart from other cells types is that:
- The Stem cell‘s capability of renewal into specialized cells through cell division even after long periods of inactivity.
- When induced, either under physiologic or experimental conditions, stem cells are capable of developing into tissue or organ specific cells with specialized functions.
The foundation for stem cell research was based on extensive work on two types of stem cells:
- Embryonic stem cells (ESC’s)
- Non embryonic/somatic/adult cells
Stem cells derived from human embryo are called Human Embryonic Stem Cells(hESC’s).
A 2006 breakthrough provided researchers a new tool to make successful strides in stem cell research; it was discovered that other specialized cells can be “reprogrammed” genetically to assume stem cell like state. These cells are called ‘induced pluripotent stem cells’ (iPSCs).
To engineer stem cells into novel therapies, scientists are striving to understand their framework and processes, and yield information regarding cell division and differentiation.
ESCs and iPSCs are attractive cell types in regenerative medicine because of their ability to self renew and differentiate into different germ layers. Wnt/β catenin signalling pathway plays an important role in maintaining self renewal and pluripotency of mouse embryonic stem cells (mESCs). Signaling by the Wnt family of secreted glycolipoproteins is one of the fundamental mechanisms that direct cell proliferation, cell polarity, and cell fate determination during embryonic development and tissue homeostasis. As a result, mutations in the Wnt pathway are often linked to human birth defects, cancer, and other diseases
If Wnts are not expressed or if their binding to receptors is inhibited, degradation of β-catenin is facilitated via interactions with a protein complex consisting of adenomatous polyposis coli (APC), axin, and glycogen synthase kinase 3 (GSK3). APC and axin act as scaffold proteins allowing GSK3 to bind and phosphorylate β-catenin, identifying it for degradation by the β-TrCP–mediated ubiquitin/proteasome pathway.
CHIR99021 is a synthetic small molecule that inhibits GSK3 and indirectly plays a crucial role in cell differentiation, maintenance, chemical and lineage reprogramming of various cells.
CHIR99021 activates Wnt-signaling by binding secreted Wnt-protein to its receptor, disheveled (Dvl/Dsh) is recruited and inhibits the GSK3 located in the beta-catenin destruction complex. This leads to an accumulation of free non-phosphorylated beta-catenin in the cytosol, which translocates to the nucleus and transactivates Wnt-target genes together with the T-cell factor (TCF)/lymphoid-enhancing factor (LEF) family of transcription factors. Thus, chemical inhibition of the GSK3 leads to a pharmacological activation of the canonical Wnt-signaling pathway.
Several studies on mouse and rat ES cells have proved CHIR99021 to be a potent pharmacological activator of Wnt/beta-catenin pathway. The high potency is combined with very low toxicity. Therefore, CHIR99021 a potent and highly selective Glycogen Synthase Kinase 3 inhibitor has the ability to modulate and control the fate of embryonic stem cells and proves to be an essential tool for stem cell research!
We at AG Scientific, Inc. take pride in being part of the scientific community and provide tools like CHIR99021 to make revolutionary discoveries in stem cell research. To learn more and to get information about pricing and deals on CHIR99021 Click here.
Canonical/β-Catenin Wnt Pathway Activation Improves Retinal Pigmented Epithelium Derivation From Human Embryonic Stem Cells
Lyndsay L. Leach; David E. Buchholz; Vignesh P. Nadar; Stefan E. Lowenstein; Dennis O. Clegg
GSK3 inhibitors CHIR99021 and 6-bromoindirubin-3′-oxime inhibit microRNA maturation in mouse embryonic stem cells-Yongyan Wu,Fayang Liu, Yingying Liu, Xiaolei Liu, Zhiying Ai,Zekun Guo & Yong Zhang
Differentiation of Cardiomyocytes from Human Pluripotent Stem Cells Using Monolayer Culture-Ivan Batalov1 and Adam W Feinberg
Stem Cell Basics- National Institutes of Health
Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors-Naujok O1, Lentes J, Diekmann U, Davenport C, Lenzen S.
Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming Wenlin Li and Sheng Ding-Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.