GMP Stem Cell Compounds

Stem cells are defined by their ability to differentiate into specialized cells and to self-renew. Small molecules are used in many protocols for cell reprogramming, differentiation and proliferation, and present advantages over typical exogenous gene expression methods.

GMP (Good Manufacturing Practice) is a set of harmonized guidelines to ensure safe, reliable, consistent and quality-assured products. The GMP stem cell compounds listed below are suitable for use as ancillary reagents (raw materials) for the further manufacture of stem cell therapies. The compounds Y-27632 (ROCK inhibitor), CHIR 99021 (WNT pathway activator) and XAV 939 (WNT signaling inhibitor) will be produced to GMP specifications later in the year.

Products
Background
Cat No Product Name / Activity
TB2634-GMP DAPT
DAPT synthesized to cGMP guidelines
TB1614-GMP SB 431542
SB 431542 synthesized to cGMP guidelines

Stem 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).

Typically, reprogramming of somatic cells and differentiation of PSCs into terminal lineages has been achieved through exogenous gene expression, via retroviral transfer. However, small molecules present advantages over gene expression methods. They are easy to use and convenient, and can greatly reduce the time associated with stem cell differentiation, reprogramming and proliferation. The effects of small molecules are reversible and concentration dependent, meaning their effects can be applied for a short time period, and in multiple different protocols with different outcomes.

GMP (Good Manufacturing Practice) is a set of harmonized guidelines that set out procedures to ensure safe, reliable, consistent and quality-assured products. The clinical phase of stem cell therapy development is highly regulated, meaning there is a requirement for GMP ancillary reagents (raw materials) to assure therapy suitability and safety.

The aim of stem cell therapy is to replace unhealthy or lost cells with new cells, giving it applications in a range of disorders including neurodegenerative diseases. Protocols for the neural induction of stem cells with small molecules have recently been developed. A combination approach of small molecule inhibitors can induce post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation. These neurons, implanted at day 8 of differentiation into the mouse cortex form functional, long distance projections. This indicates that stem cell derived neurons could be transplanted to replace lost neurons. A recent search of Clinicaltrials.gov indicates that there are approximately 10 clinical trials, either completed or recruiting patients, to investigate the transplantation of stem cell-derived neural precursors or neurons in neurological disorders such as Parkinson's disease and spinal cord injury.

For examples of how small molecules can be used in place of or in combination with growth factors and other proteins in cell culture, please see our stem cell protocol snapshots.

For more information about the advantages of using small molecules in stem cell methods, please see our blog post.