Combining stem cell and drug delivery to modulate macrophage phenotype toward M2 in spinal cord injury
It has recently been shown that M2 macrophages in the central nervous system (CNS) resolve microglial and astrocyte inflammation, promote neuroprotection and axonal regeneration and support differentiation of neural progenitor cells [1, 2]. However, the local microenvironment within a CNS lesion does not allow conversion to an M2 macrophage phenotype . Instead, the lesion site following CNS injury is typically dominated by M1 macrophages that create a highly inflammatory, neurotoxic environment that prevents restitution of functional tissue.
We hypothesize that macrophages present at the spinal cord lesion could be polarized towards an M2 phenotype by combining decellularized spinal cord extracellular matrix–based hydrogel (SC-dECMh) with IL-4 and dental stem cell delivery. Hence, this project will study the impact of SC-dECMh loaded with IL-4 and dental stem cells on microglia and circulating macrophage phenotype to improve spinal cord repair.
The specific aims of this project will be i) to demonstrate the ability of SC-dECMh and dental stem cells from the apical papilla (SCAP) to individually polarize macrophages and microglia towards an M2 phenotype, ii) to optimize the combination of the three components to obtain the most potent and lasting effect and iii) to demonstrate the efficiency of the system ex vivo and in vivo.
The project will be carried out within the Tissue Engineering group within the Division of Drug Delivery and Tissue Engineering. The School of Pharmacy provides excellent cross-disciplinary support and training facilities for PG students.
This project is jointly funded by the Institute for Research in Paraplegia (IRP) and the School of Pharmacy. A three year studentship is available with initial yearly stipend of £14,002 with incremental increases for the subsequent years. Tuition fees of £4060 will also be covered by project funding.
Applications are welcome from motivated students with a good honours BSc. or Masters degree in Science subjects.
1. Zhang, Y.K., et al., The effect of Lycium barbarum on spinal cord injury, particularly its relationship with M1 and M2 macrophage in rats. BMC Complement Altern Med, 2013. 13: p. 67.
2. Miron, V.E., Dissecting the damaging versus regenerative roles of CNS macrophages: implications for the use of immunomodulatory therapeutics. Regenerative Medicine, 2013. 8(6): p. 673-676.
3. Shechter, R., et al., Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med, 2009. 6(7): p. e1000113.
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