Nanotechnology has been a buzzword in the medical technology community for some time. It is defined as the manipulation and use of microscopic structures at the molecular scale, generally 1-100 nanometres in size (1 nanometre is 1 billionth of a metre, which translates to approximately 1 billionth the length of a baseball bat!)
Nanotechnology is currently applied to a wide variety of experimental medical strategies including diagnostic imaging, delivery of antimicrobial agents to wounds and drug delivery. In regenerative medicine, nanotechnology has been used to promote cellular growth and differentiation through the use of nano-textured surfaces and the generation of nano-structured molecules.
Over the last few years, Samuel Stupp of Northwestern University has been developing unique nanofibres that can self-assemble into a three-dimensional network (or scaffold). While in solution, these nanofibres can be turned into a gel by changing parameters such as pH or temperature. Cells present in the nanofibre solution can be encapsulated within the gel and thus become surrounded by a supportive artificial environment.
Stupp’s gelled nanofibres have been coined ‘noodle gels’ or ‘spaghetti highways’ because of their long cylindrical nature and ability to house and direct cells within a tissue. Stupp’s company, Nanotope, formed on the basis of this technology, aims to tackle an array of regenerative medicine markets including spinal cord regeneration, wound healing and cartilage regeneration.
Stupp’s most recent work, carried out in his academic laboratory, aims to apply this nanofibre technology to pancreatic cell biology. Published this month in Acta Biomaterialia, ‘noodle gel’ technology was used to create insulin-stimulating, cell-protective, fully degradable scaffolds for the delivery of pancreatic cells.
Nanofibres were designed to incorporate a peptide mimetic of glucagon-like peptide 1 (a hormone produced by your gut that is cued by eating). The incorporation of glucagon-like peptide 1 stimulates long-term insulin production, inhibits cell death and encourages cell growth. These modified ‘noodle gels’ were found to stimulate insulin production in rat pancreatic cells at a greater level than the clinically-used glucagon-like peptide 1 agonist exedin-4 (which promotes glucose-dependent insulin secretion).
For type I diabetes, the hope is to incorporate ‘noodle gel’ technology into current pancreatic islet cell transplantation procedures to enhance beta cell (insulin-secreting cell) function and viability.
The Edmonton Protocol (developed by Canadian researchers in 2000) is a method for pancreatic islet cell transplantation. Transplantation of donor pancreatic islets into type I diabetes patients provides short-term insulin independence for most patients. However, a long-term follow up study reported a loss of insulin-independence in 90% of transplant recipients five years following transplantation. This loss of insulin-independence can be attributed to a number of pathophysiological processes including cell death and impaired insulin secretion – both of which could be resolved using ‘noodle gel’ technology.
While ‘noodle gels’ provide promise for improved islet cell transplantation, we are still faced with a shortage of donor islets. A long-term application goal of this technology is to encapsulate and deliver stem cell-derived pancreatic beta cells or even pancreatic progenitor cells capable of differentiating in vivo.
When thinking about regenerative medicine strategies for the future, it seems to me that approaches combining stem cell biology and biomaterials science such as this hold the most promise for cell replacement strategies to treat many diseases, including type I diabetes.
Angela C. H. McDonald
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