AsianScientist (Aug. 14, 2013) – Stem cell therapy has the potential to repair and regenerate damaged tissues. However, implanted cells might be rejected, migrate or die; tracking stem cells in vivo may help to further understand what happens once these cells are inside the host.
A team of scientists from Taiwan, led by Dr. Huan-Cheng Chang of Academia Sinica, developed a new stem cell isolation method for lung stem cells (LSCs), using cell surface glycoprotein markers discovered by specialized proteomic analysis.
In their work, published in the journal Nature Nanotechnology, they demonstrate that cells isolated with this method possess not only the ability to self-renew and differentiate into lung tissues, but also to home and regenerate in vivo, as expected of a LSC.
Next, they used fluorescent nanodiamonds (FNDs) to label these cells. FNDs are novel imaging probes which are not only chemically robust and fluorescently stable, but also biologically inert and nontoxic. These nanoparticles can be readily taken up by cells through endocytosis.
Armed with this technique, the scientists showed that FND-labeled lung stem cells preferentially home to injured lungs more rapidly than to uninjured controls, enabling the lung epithelium to be restored more rapidly. In addition to demonstrating the therapeutic potential of such treatment, these results also support an “active homing” model in which transplanted LSCs proactively migrate to injured tissue, as opposed to non-specific/passive entrapment.
Speaking with Asian Scientist Magazine, Dr. Chang says, “By labeling lung stem/progenitor cells with red fluorescent nanodiamonds, we showed that the position of the transplanted cells can be precisely identified in the tissue sections of mice with single-cell resolution. The identification is crucial to determine the tissue-specific engraftment and regenerative capacity of the transplanted stem cells in vivo. The optical imaging technique developed in this work is complementary to magnetic resonance imaging (MRI) and provides an exciting new opportunity to study stem cells transplanted into animals in an unprecedented detail.”
According to Dr. Chang, the inspiration to use FNDs came from recent evidence that low-dimensional nanoparticles, such as carbon nanotubes and graphene, are cytotoxic and can cause inflammatory responses in the body.
“In comparison, nanodiamonds composed solely of sp3-hybridized carbon atoms are inherently biocompatible and non-toxic. Moreover, the color centers built in the particles can emit perfectly stable far-red fluorescence with distinct lifetimes,” he explains.
One of the major challenges the researchers had to overcome was the strong autofluorescent background of host tissue. They took advantage of the fact that the FNDs emit stable far-red emission with a fluorescence lifetime of up to 15 ns, much longer than endogenous and exogenous fluorophores commonly used in cell biology. This property made it possible to design special strategies to separate FND emission from autofluorescent background.
Looking forward, Dr. Chang hopes to apply this technology to other stem cell types.
“Our future plans are to demonstrate that the method developed in this work is general and can be applied to other stem cell systems (including neural and bone marrow stem cells) as well. The nanodiamond-based platform is particularly suitable for the studies of rare stem cells that are difficult to be transfected to express fluorescent proteins or non-fluorescent compounds, such as human stem cells,” he tells Asian Scientist Magazine.
The article can be found at: Wu TJ et al. (2013) Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds.
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Copyright: Asian Scientist Magazine; Photo: NPG.
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