Macrophage-Derived Inflammation Induces a Transcriptome Makeover in Mesenchymal Stromal Cells Enhancing Their Potential for Tissue Repair.

Pre-clinical and clinical studies revealed that mesenchymal stromal cell (MSC) transplants elicit tissue repair. Conditioning MSC prior to transplantation may boost their ability to support repair. We investigated macrophage-derived inflammation as a means to condition MSC by comprehensively analyzing their transcriptome and secretome. Conditioning MSC with macrophage-derived inflammation resulted in 3208 differentially expressed genes, which were annotated with significantly enriched GO terms for 1085 biological processes, 85 cellular components, and 79 molecular functions. Inflammation-mediated conditioning increased the secretion of growth factors that are key for tissue repair, including vascular endothelial growth factor, hepatocyte growth factor, nerve growth factor and glial-derived neurotrophic factor. Furthermore, we found that inflammation-mediated conditioning induces transcriptomic changes that challenge the viability and mobility of MSC. Our data support the notion that macrophage-derived inflammation stimulates MSC to augment their paracrine repair-supporting activity. The results suggest that inflammatory pre-conditioning enhances the therapeutic potential of MSC transplants.

Comparisons of guardianship laws and surrogate decision-making practices in China, Japan, Thailand and Australia: a review by the Asia Consortium, International Psychogeriatric Association (IPA) capacity taskforce.

BACKGROUND: The International Psychogeriatric Association (IPA) capacity taskforce was established to promote the autonomy, proper access to care, and dignity of persons with decision-making disabilities (DMDs) across nations. The Asia Consortium of the taskforce was established to pursue these goals in the Asia-Pacific region. This paper is part of the Asia Consortium's initiative to promote understanding and advocacy in regard to surrogate decision-making across the region. METHOD: The current guardianship laws are compared, and jurisdictional variations in the processes for proxy decision-making to support persons with DMDs and other health and social needs in China, Japan, Thailand, and Australia are explored. RESULTS: The different Asia-Pacific countries have various proxy decision-making mechanisms in place for persons with DMDs, which are both formalized according to common law, civil law, and other legislation, and shaped by cultural practices. Various processes for guardianship and mechanisms for medical decision-making and asset management exist across the region. Processes that are still evolving across the region include those that facilitate advanced planning as a result of the paucity of legal structures for enduring powers of attorney (EPA) and guardianship in some regions, and the struggle to achieve consensual positions in regard to end-of-life decision-making. Formal processes for supporting decision-making are yet to be developed. CONCLUSIONS: The diverse legal approaches to guardianship and administration must be understood to meet the challenges of the rapidly ageing population in the Asia-Pacific region. Commonalities in the solutions and difficulties faced in encountering these challenges have global significance.

Markerless tracking enables distinction between strategic compensation and functional recovery after spinal cord injury.

Injuries to the cervical spinal cord represent around 60% of all spinal cord injuries (SCIs). A major priority for patients with cervical SCIs is the recovery of any hand or arm function. The similarities between human and rodent "reach-to-eat movements" indicate that analyzing mouse forelimb reaching behavior may be a method of identifying clinically relevant treatments for people with cervical SCIs. One popular behavioral measure of forelimb functional recovery comprises the Single Pellet Retrieval Task (SPRT). The most common outcome measure for this task, however (percentage of pellets successfully retrieved), cannot readily distinguish between recovery of pre-injury motor patterns and strategic compensation. Our objective was to establish outcome measures for the SPRT that are readily adopted by different investigators and capable of measuring recovery of limb function after SCI. We used a simple semi-automated approach to high-speed tracking of mouse forepaw movements during pellet retrieval. DeepLabCut™, a machine learning based computer vision software package, was used to track individual features of the mouse forepaw, allowing a more detailed assessment of reaching behavior after SCI. Interestingly, kinematic analysis of movements pre- and post-injury illuminated persistent deficits in specific features of the reaching motor patterns, namely pronation and paw trajectory, that were poorly correlated with recovery of the ability to successfully retrieve pellets. Thus, we have developed an inexpensive method for detailed analysis of mouse reach-to-eat behavior following SCI. Further, our results suggest that binary success/fail outcome measures primarily assess an animal's ability to compensate rather than a restoration of normal function in the injured pathways and networks.

Can Chromatin Accessibility be Exploited for Axon Regeneration?

Several studies have demonstrated that the intrinsic ability of neurons to regenerate their axons can be stimulated by maneuvers that favor the open state of chromatin, such as inhibiting histone deacetylase activity or increasing histone acetyltransferase activity. Taken together, these experiments suggest that axon regenerative ability can be increased by promoting chromatin accessibility. In this article, we assess the direct evidence in the literature for this hypothesis and re-examine other axon regeneration-promoting manipulations to see if they provide additional support. We find that several interventions known to enhance intrinsic axonal growth capability also increase chromatin accessibility. Although the support for this correlation is strong in the literature, we conclude with a word of caution about therapeutics attempting to exploit this relationship.