Nanotechnology and Stem Cell Applications
Nanotechnology and biomedical treatments using stem cells (such as therapeutic cloning) are among the newest veins of biotechnological research. Even more recently, scientists have begun finding ways to marry the two. Since about 2003, examples of nanotechnology and stem cells combined have been accumulating in scientific journals. While the potential applications for nanotechnology in stem cell research are countless, three main categories can be assigned to their use:
- tracking or labeling
Certain nanoparticles have been in use since the 1990's, for applications such as cosmetic/skin care delivery, drug delivery and labeling. Experimentation with different types of nanoparticles such as quantum dots, carbon nanotubes and magnetic nanoparticles, on somatic cells or microorganisms, has provided the background from which stem cell research has been launched. It's a little-known fact that the first patent for the preparation of nanofibers was recorded in 1934. These fibers would eventually become the foundation of scaffolds for stem cell culture and transplantation—over 70 years later.
Visualizing Stem Cells Using MRI and SPIO Particles
Research on the applications of nanoparticles for magnetic resonance imaging (MRI) has been pushed by the need to track stem cell therapeutics. A common choice for this application is superparamagnetic iron oxide (SPIO) nanoparticles, which enhance the contrast of MRI images. Some iron oxides have already been approved by the FDA. The different types of particles are coated with different polymers on the outside, usually a carbohydrate. MRI labeling can be done by attaching the nanoparticles to the stem cell surface or causing uptake of the particle by the stem cell through endocytosis or phagocytosis. Nanoparticles have helped add to our knowledge of how stem cells migrate in the nervous system.
Labeling Using Quantum Dots
Quantum dots (Qdots) are nano-scale crystals that emit light and are comprised of atoms from groups II-VI of the periodic table, often incorporating cadmium. They are better for visualizing cells than certain other techniques such as dyes, because of their photostability and longevity. This also allows their use for studying cellular dynamics while differentiation of stem cells is in progress.
Qdots have a shorter track record for use with stem cells than SPIO/MRI and have only been used in vitro so far, because of the requirement for special equipment to track them in whole animals.
Nucleotide Delivery for Genetic Control
Genetic controls, using DNA or siRNA (not to be confused with miRNA), is emerging as a useful tool for controlling cellular functions in stem cells, particularly for directing their differentiation. Nanoparticles can be used to replace the traditionally used viral vectors, such as retroviruses, which have been implicated in causing complications in whole organisms such as inducing mutations leading to cancer. Nanoparticles offer a less expensive, more easily producible vector for transfection of stem cells, with a lower risk of immunogenicity, mutagenicity or toxicity. A popular approach is to use cationic polymers that interact with DNA and RNA molecules. There is also room for the development of smart polymers, with features such as targeted delivery or scheduled release. Carbon nanotubes with different functional groups have also been tested for drug and nucleic acid delivery into mammalian cells, but their use in stem cells has not been investigated to a large extent.
Optimizing the Stem Cell Environment
A significant area of study in stem cell research is that of the extracellular environment and how conditions outside the cell send signals for the control of differentiation, migration, adhesion and other activities. The extracellular matrix (ECM), consists of molecules secreted by cells such as collagen, elastin, and proteoglycan. The properties of these excretions and chemistry of the environment they create, provide direction for stem cell activities. Nanoparticles have been used to engineer differently patterned topographies that mimic the ECM, for studying their effects on stem cells.
A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. Nanoscale scaffolds improve cell survival by aiding the engrafting process. Nanofibers spun from synthetic polymers such as poly(lactic acid) (PLA), or natural polymers of collagen, silk protein or chitosan, provide channels for alignment of stem and progenitor cells. The ultimate goal is to determine what scaffold composition best promotes proper adhesion and proliferation of the stem cells and use this technique for stem cell transplantations. However, it appears the morphology of cells grown on nanofibers may differ from cells grown on other media, and few in vivo studies have been reported.
Nanoparticle Toxicity to Stem Cells
As with all biomedical discoveries, use of nanoparticles for these applications in vivo (in humans) requires the approval of the FDA. With the discovery of the potential of nanoparticles for stem cell applications, has come an escalating demand for clinical trials to test the new discoveries and increasing interest in nanoparticle toxicity.
The toxicity of SPIO nanoparticles has been studied to a large extent. For the most part, they have not appeared toxic, but one study has suggested an effect on the differentiation of stem cells. However, there is still some uncertainty as to whether toxicity was caused by the nanoparticles or the transfection agent/compound.
Toxicity data for Qdots is scarce, but what data there are do not all agree. Some studies report no adverse effects on stem cell morphology, proliferation, and differentiation, while others report abnormalities. The differences in test results could be attributed to the different compositions of the nanoparticles or target cells, therefore much more research is needed to establish what is safe and what is not, and for what types of cells. What is known is that oxidized cadmium (Cd2+) can be toxic because of its effect on the mitochondria of cells. This is further complicated by the release of reactive oxygen species during Qdot degradation.
Carbon nanotubes appear to be generally genotoxic, depending on their shape, size, concentration and surface composition, and might contribute to the generative of reactive oxygen species in cells.
Nanoparticles are promising tools for new biomedical techniques, due to their small size and ability to penetrate cells. As research advances continue to add to our knowledge of the factors controlling stem cell functions, it is likely that new applications for nanoparticles, in concert with stem cells, will be discovered. While the evidence suggests that some applications will turn out to be more useful, or safer, than others, there is enormous potential for using nanoparticles to enhance and improve stem cell technologies.
Ferreira, L. et al. 2008. New opportunities: The use of nanotechnologies to manipulate and track stem cells. Cell Stem Cell 3:136-146. doi:10.1016/j.stem.2008.07.020.