New tools and therapies for peripheral nerve regeneration
My research interest focuses in the study of novel therapies for nerve regeneration and re-myelination following injury. These therapies could involve a wide range of approaches including stem cell intervention, pharmacological intervention and the development of novel biomaterials for nerve engineering.
Stem cell therapies
Peripheral nerve injuries occur with high incidence and often result in profound and permanent impact on the life of patients and on healthcare expenditure. Schwann cells (SC) play a promoting role in peripheral nerve regeneration providing physical and neurotrophic support that aids axon re-growth. However, these beneficial properties are not exploitable in nerve tissue engineering due to the difficulties in SC harvesting and expansion in culture. Adult stem cells derived from the adipose tissue (ASC) can be differentiated in SC-like cells and be used as SC substitutes in regerative medicine approaches for nerve repair. We have recently shown that human ASCs can be chemically stimulated to create highly neurotrophic cells, however we are still far from terminal SC differentiation. Current research is focused on improving our differentiation protocols through pharmacological intervention, biomaterials interaction and gene editing.
Pharmacological intervention approaches for the treatment of nerve injury are still not clinically available. Nevertheless, neurotransmitter receptors have been recently suggested as a putative target for such purpose. My research is focused on the study of neurotransmitter receptors in SC and ASC differentiated into a SC-like phenotype. Functional neurotransmitter receptors on SC and SC-like adult stem cells could represent an exploitable pharmacological target to modulate cell physiology and improve ASC neurotrophic potential during peripheral nerve regeneration. In particular, I study the role of GABA, purinergic and muscarinic receptors to modulate the physiology of endogenous SC and to improve survival and differentiation of ASCs prior to transplantation.
Biomaterials for nerve engineering
In order to create a bioengineered nerve graft it is necessary to develop a biocompatible, cheap and versatile material, which can constitute the nerve guidance tube. The commercially available options fail to address the biology of nerve regeneration. We have developed a synthetic, polymer-based nerve conduit that showed performances comparable to nerve auto-grafting and great promise for clinical translation. We are now looking to include cell delivery within the nerve guidance tube by using hydrogel-based approaches. Finally, we are exploiting the versatility of graphene-based scaffolds to direct stem cell differentiation and aid delivery within nerve guidance tubes.
Culture of neuronal and glial cells of the peripheral nervous system (dorsal root ganglia neurons and Schwann Cells).
Culture and differentiation of adult stem cells derived from the bone marrow and from the adipose tissue.
Molecular biology techniques (PCR, Western blot and immunohistochemistry).
Confocal and electron mycroscopy.
Fluorescence video imaging of intracellular calcium.