Is it destiny or can science treat disease by changing cell fate?Posted: 09 02, 2015
Written by Christina Marvin
Illustration by Christina Marvin
Human embryonic stem cells (hESCs) are extraordinary in that they have the potential to differentiate into any somatic cell type and thus are used as effective tools in a wide range of studies, from understanding basic scientific processes to discovering treatment for disease. Yet, there is a great deal of controversy when embryonic stem cells are used in scientific research, especially considering the difficult ethical questions involved with using human embryonic tissue for research. However, did you know that recent studies have demonstrated that altering cell identity may not require the use of this material at all? There is substantial research focused on the use of adult progenitor cells for the purpose of re-directing cell fate. These cell types are less primitive than embryonic stem cells but still maintain a certain level of plasticity that allows their final identity to be genetically altered.1 This ability sounds like something your favorite cell-altering science fiction character would possess, but can it be useful in treating disease? If scientists had the ability to morph easily obtainable adult cells into a type that is much harder to procure (i.e. neural cells), more comprehensive investigations could be performed in areas such as regenerative medicine and drug discovery, thus stimulating greater strides in these fields.
Dr. Mickie Bhatia’s group from McMaster University in Ontario, Canada has generated an approach that combines two previously developed techniques in order to promote direct conversion of adult human blood progenitor cells into neural progenitor cells – a blood to brain cell conversion!2 The first technique is “OCT4-induced plasticity reprogramming.”3 OCT4 is a transcription factor whose brief expression converts cells into a “plastic state” in which they have the ability to differentiate into other cell types, a process of which terminally differentiated cells are incapable. Unfortunately, this technique only serves to de-differentiate somatic cells, and does not commit them to a particular lineage. Bhatia’s group combined OCT4-induced plasticity reprogramming with previously identified small molecules that specifically induce neural potentiating cells. These molecules are chemical inhibitors of SMAD proteins and the enzyme glycogen synthase kinase-3 (GSK3). Previous studies4 show that inhibiting the signaling of these molecules effectively promotes the differentiation of neurons from pluripotent human cells. Thus, by combining the techniques described above, the Ontario group demonstrated that they can induce plasticity in adult somatic cells while directing them to a neural cell potentiation state.
What makes this work particularly exciting is that the blood-derived induced-neural progenitor cells (BD-iNPCs) are capable of in vivo differentiation and survival, as well as tripotent neural differentiation in vitro. That is, the newly derived neural progenitor cells could develop into multiple possible functional neuron types including glia (astrocytes and oligodendrocytes) and neuronal subtypes that are central nervous system (CNS) and peripheral nervous system (PNS) related. Thus far, much work on the direct conversion of cells to the neural lineage has been restricted to using neonatal cord blood-derived mesenchymal stem cells, while other attempts have resulted in neural progenitor cells with only limited differentiation ability. To this day, BD-iNPCs are the first of their kind: tripotent neural progenitor cells derived directly from adult human blood. Unlike human neurons, blood is abundant, easy to collect, and induces little to no distress on the patient when drawn. If adult blood could be harvested as a substitute for neural cells, materials for pre-clinical studies in the development of life-saving therapies for brain injuries and many other neurological conditions could be available to more researchers in more labs, advancing the rate of treatments and cures. Is a young cell’s final form rooted in destiny? Dr. Bhatia’s study suggests that science may have unlocked an easier way to create specific, difficult-to-acquire cell types from those that are commonly available. Furthermore, this technology holds potential to enhance research programs focused on treating devastating illnesses.
- “What are Progenitor Cells.” Boston Children’s Hospital. Web. <http://stemcell.childrenshospital.org/about-stem-cells/adult-somatic-stem-cells-101/what-are-progenitor-cells/>.
- Lee J.H., Mitchell R.R., McNicol J.D., Shapovalova Z., Laronde S., Tanasijevic B., Milsom C., Casado F., Fiebig-Comyn A., Collins T.J., Singh K.K., and Bhatia M. Single transcription factor conversion of human blood fate to NPCs with CNS and PNS developmental dapacity. Cell Rep. 11, 1367 – 1376 (2015).
- Mitchell R., Szabo E., Shapovalova Z., Aslostovar L., Makondo K., and Bhatia M. Molecular evidence for OCT4-induced plasticity in adult human fibroblasts required for direct cell fate conversion to lineage specific progenitors. Stem Cells. 32, 2178 – 2187 (2014).
- Chambers S.M., Fasano C.A, Papapetrou E.P., Tomishima M., Sadelain M., and Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 27, (2009).
Peer edited by Ashley Fuller & Laura Taylor
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This article was co-published on the SWAC Blog, The Pipettepen.