Targeting Matrix Metalloproteinases: A Potential Strategy for Improving Cell Transplantation for Nervous System Repair.

Cell transplantation shows promise for repair of the injured nervous system, including spinal cord injury (SCI) and peripheral nerve injury (PNI). There are, however, still problems hampering these therapies moving from bench to bedside, and the methods need optimization. Three-dimensional (3D) cell culture systems are suggested to improve outcomes, bridging the gap between the in vitro and in vivo environments. In such constructs, cells are allowed to interact with each other and with the extracellular matrix (ECM) in 3D as they do in vivo. Transplanting cells in 3D constructs, rather than in suspension, is thought to promote cell survival and maintain important cellular behaviors. One such critical behavior is cell migration into and within the injury site. Understanding and controlling the migratory capability of 3D-cultured cells is therefore pivotal for developing better transplantation techniques. ECM remodelling can influence numerous cellular functions, including cell migration and matrix metalloproteinases (MMPs) are important enzymes for ECM modulation. Here, we discuss the idea of modulating MMPs to control cell migration in 3D culture systems, which can improve the therapeutic potential of cells transplanted in 3D.

The Glia Response after Peripheral Nerve Injury: A Comparison between Schwann Cells and Olfactory Ensheathing Cells and Their Uses for Neural Regenerative Therapies.

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory nerve, and Schwann cells (SCs), which are present in the rest of the PNS. These two glial types share many similar morphological and functional characteristics but also exhibit key differences. The olfactory nerve is constantly turning over throughout life, which means OECs are continuously stimulating neural regeneration, whilst SCs only promote regeneration after direct injury to the PNS. This review presents a comparison between these two PNS systems in respect to normal physiology, developmental anatomy, glial functions and their responses to injury. A thorough understanding of the mechanisms and differences between the two systems is crucial for the development of future therapies using transplantation of peripheral glia to treat neural injuries and/or disease.

Digital microfluidics with a magnetically actuated floating liquid marble.

Controlled actuation of a floating liquid marble, a liquid droplet coated with hydrophobic particles floating on another liquid surface, is a potential digital microfluidics platform for the transport of aqueous solution with minimal volume loss. This paper reports our recent investigation on the magnetic actuation of floating liquid marbles filled with magnetic particles. The magnetic force and frictional force acting on the floating liquid marble determine the horizontal movement of the marble. We varied the magnetic flux density, flux density gradient, concentration of magnetic particles and speed of the marble to elucidate the relationship between the acting forces. We subsequently determined the suitable operating conditions for the actuation and derived the scaling laws for the actuation parameters.

Colorectal cancer screening in Australia: an economic evaluation of a potential biennial screening program using faecal occult blood tests.

OBJECTIVE: To evaluate whether the introduction of a national, co-ordinated screening program using the faecal occult blood test represents 'value-for-money' from the perspective of the Australian Government as third-party funder. METHODS: The annual equivalent costs and consequences of a biennial screening program in 'steady-state' operation were estimated for the Australian population using 1996 as the reference year. Disability-adjusted life years (DALYs) and the years of life lost (YLLs) averted, and the health service costs were modelled, based on the epidemiology and the costs of colorectal cancer in Australia together with the mortality reduction achieved in randomised controlled trials. Uncertainty in the model was examined using Monte Carlo simulation methods. RESULTS: We estimate a minimum or 'base program' of screening those aged 55 to 69 years could avert 250 deaths per annum (95% uncertainty interval 99-400), at a gross cost of dollarsA55 million (95% UI dollarsA46 million to dollarsA96 million) and a gross incremental cost-effectiveness ratio of dollarsA17,000/DALY (95% UI dollarsA13,000/DALY to dollarsA52,000/DALY). Extending the program to include 70 to 74-year-olds is a more effective option (cheaper and higher health gain) than including the 50 to 54-year-olds. CONCLUSIONS: The findings of this study support the case for a national program directed at the 55 to 69-year-old age group with extension to 70 to 74-year-olds if there are sufficient resources. The pilot tests recently announced in Australia provide an important opportunity to consider the age range for screening and the sources of uncertainty, identified in the modelled evaluation, to assist decisions on implementing a full national program.