Stem cell therapy could unlock new regenerative treatments for repairing tissue, but large numbers of cells will be needed. Now researchers have developed a simple, cheap and biocompatible cell culture substrate that uses gold nanorods to unlock stem cells in potentially large numbers [Vegi et al., Acta Biomaterialia 129 (2021) 110-121,].

“We developed an enzyme-free method of harvesting clinically valuable stem cells from substrates… because traditional enzymatic methods… can damage or even kill cells if they are exposed to enzymes for too long,” explains Nicholas P. Reynolds of La Trobe University who, together with Simon Moulton of Swinburne University of Technology, led a team of collaborators from Peter MacCallum Cancer Centre, St Vincent’s Hospital, and the University of Melbourne in Australia.

The new approach relies on gold nanorods deposited in a thin layer on a glass substrate to which they adhere strongly. When the nanorods are irradiated with a near infrared (NIR) laser at a biocompatible low intensity, surface electrons become excited in a process known as localized surface plasmon resonance (LSPR). Because of the shape of nanorods, the energy produced by LSPR is concentrated at the tips, producing highly localized heating. This heating, which only affects the interface between nanorods and the cells growing on the substrate, gently detaches the cells.

“If the nanorods were not present, similar heating effects would damage the cells and not promote cell detachment,” says Reynolds. “The gold nanorods provide a way to localize the heating so that cell survival is ensured while also initiating cell detachment.”

Human bone marrow-derived mesenchymal stem cells grown on the new substrate and detached using the gold nanorod photothermal method are as or more viable and able to differentiate into clinically useful osteo cells for bone regrowth or energy-storing adipocytes than those from traditional enzymatic methods.

“Our approach is synthetically very simple, the gold nanorods spontaneously attach to the glass substrate, and remain attached to the substrate after NIR simulation and cell harvesting, and are not taken up by the cell,” adds Yashaswini Vegi, first author of the study.

The method has the potential to be scaled up and used as an inexpensive alternative to enzymatic cell harvesting, while avoiding the complexity and problems of other non-enzymatic methods.

“If tissue regeneration treatments become commonplace, vast numbers of cells will be required and enzymatic harvesting of these cells may be expensive and problematic,” says Reynolds. “We think, with some modifications, [our] approach could be useful for harvesting the very large numbers of cells [that] will be required for regenerative medical applications. Our technique has the potential to be many times less expensive than the cost of enzymatic cell detachment.”

Although the new approach is slower than enzymatic techniques, the researchers believe that optimizing the laser activation and nanorods morphology will reduce the cell harvesting time. Larger area NIR light sources such as arrays of LEDs could also be useful for detaching larger numbers of cells.

Laser-mediated stem cell harvesting. Image adapted from original artwork created by Marion Dubois.
Laser-mediated stem cell harvesting. Image adapted from original artwork created by Marion Dubois.