In the first part, we outlined the steps in differentiation of pluripotent stem cells to pancreatic β cells. Here, we discuss how patient-specific pluripotent stem cells provide better therapeutic options.
Diabetes mellitus has several forms, which are broadly classified into type 1 (T1D) and type 2 (T2D). T2D accounts for ~90% of diabetic cases worldwide and is sub-classified into several forms including neonatal diabetes mellitus (NDM) and maturity onset diabetes of the young (MODY). The molecular mechanisms contributing to diabetes and the associated pathophysiology differs among the varied subtypes. Thus, availability of cells which are genetically identical to diabetic patients is a sought after tool. Such cells can be employed both in basic research and therapy. Stem cells derived from diabetic patients fulfill the criteria of genetic identity and can be used in the petri dish or engineered into pancreatic β cells for transplantation.
Pluripotent stem cells can be derived from a variety of somatic cells such as blood, keratinocytes, and hepatocytes etc (Fig 1.). Studies show that stem cells have been generated from MODY patients, which has further aided in understanding the mechanism of this disease. Also, patient specific stem cells have also been isolated from elderly patients, by effectively bypassing cellular senescence. Reprogramming of somatic cells is achieved by transfection with transcription factors (as detailed in part 1). The downside to this technique is that effective transfection is generally aided by harmful genome-integrating viruses. Integration of viruses in the stem cells can result in aberrant function, impaired differentiation and also tumorigenesis due to addition of MYC, which is known to promote cancer growth. This problem has been circumvented using: a. adenoviruses, which do not integrate, b. removal of transgenes by either Cre/LoxP recombination method or transposons, and c. direct delivery of reprogramming factors. Current research is also focused on developing effective reprogramming techniques by excluding MYC.
For all your research needs in generation of induced pluripotent stem cells, turn to HemaCare, which can also provide disease-state customized products to suit your research. Don't forget to read the third and final part in this series.
1. Essam M. Abdelalim, Amélie Bonnefond, Annelise Bennaceur-Griscelli, Philippe Froguel. Pluripotent Stem Cells as a Potential Tool for Disease Modelling and Cell Therapy in Diabetes. Stem Cell Reviews and Reports (2014) 129 (4):1102-15. doi.org/10.1007/s12015-014-9503-6