Faculty Bibliography

In diabetes, multipotent stromal cells (MSCs) are functionally deficient. It is unknown, however, whether their antibacterial function is compromised. In this study, MSCs were isolated from the bone marrow samples provided by nine diabetic and six nondiabetic donors and treated with or without Escherichia coli lipopolysaccharides (LPS). The supernatant of diabetic MSCs (MSCs-dia) and nondiabetic control MSCs (MSCs-c) was added into the cultures of E. coli for evaluation of the effect of MSCs-dia and MSCs-c on bacterial growth. The number of E. coli colonies increased when they were cultured with the supernatant of MSCs-dia, with or without LPS stimulation, compared with the E. coli cultured with the supernatant of MSCs-c. Human macrophages were co-cultured with either MSCs-dia or MSCs-c, for 24 h, and then cultured with heat-inactivated E. coli. Bacterial phagocytosis was reduced after macrophages were co-cultured with MSCs-dia. Gene expression of antibacterial peptide LL-37 and indoleamine 2,3-dioxygenase (IDO) by MSCs-dia was reduced compared with MSCs-c. The supernatant of MSCs-dia and MSCs-c was applied to a 42-cytokine antibody array. While the cytokine profiles of MSCs-dia and MSCs-c were largely similar, the productions of MCP-1 and interleukin-6 distinguished MSCs-dia from MSCs-c in response to LPS treatment. In conclusion, MSCs-dia were less inhibitive of the growth of bacteria and compromised in regulation of macrophages for bacterial phagocytosis. The reduced expression of IDO and LL-37 and an altered cytokine profile in MSCs-dia should be taken into consideration in developing cell therapies for diabetic infection.

Charcot neuroarthropathy (CNA) often presents as a diabetic foot complication. The role of synovial mesenchymal stem cells (syn-MSCs) in the pathogenesis of CNA is unclear. Synovial samples were collected, for isolation of syn-MSCs, from diabetic patients with CNA (n=7) and non-diabetic patients with intra-articular fracture or normal joints (non-CNA; n=7) during foot surgery. The syn-MSCs in the CNA and non-CNA groups were characterized comparatively. The average number of colonies formed in the CNA group was 6±3.5 per half plate (10mm in diameter), while it was 43±21.6 in the non-CNA group (p<0.05). The average size (pixels) of the colonies in the CNA group was smaller than that in the non-CNA group. When the colonies were stratified into high-, medium- and low-density subgroups, colonies in the high-density subgroup of the CNA group were reduced in density. Expression of PPAR-γ, RUNX2, Sox9 and type II collagen by syn-MSCs in the CNA group was decreased during adipogenic, osteogenic and chondrogenic differentiation as compared with the non-CNA group. In conclusion, syn-MSCs in CNA joints were reduced in number, with declined differentiation potentials. The high-density subpopulation of the syn-MSCs was particularly affected by the pathology of CNA.

The objective of this study was to investigate the efficacy of a group treatment protocol called NICE (Noticing you have a problem, Identifying the information you need for help, Compensatory strategies, Evaluating progress) to train help-seeking when wayfinding for individuals with acquired brain injury (ABI). Seven participants completed the NICE group treatment in an outpatient rehabilitation department at a university medical centre. A single subject multiple baseline design was employed to evaluate the efficacy of the NICE group treatment. The Social Behaviour Rating Scale and the Executive Function Route-Finding Task- Revised were repeated measures used to evaluate potential changes in help-seeking and wayfinding. Secondary outcome measures included pre- and post-treatment evaluation of social problem solving and social cognition. Results revealed that all participants improved on measures of help-seeking and wayfinding. Patterns of improvement and implications for rehabilitation are discussed. This is the first experimental study to evaluate the treatment of help-seeking behaviours and discuss its application to wayfinding in adults with ABI. Preliminary evidence supports further investigation of the NICE group treatment protocol.

UNLABELLED:: By using surgical mouse models, this study investigated how the tissue environment influences the osteogenic potential of muscle progenitors (m-progenitors) and potentially contributes to heterotopic ossification (HO). Injury was induced by clamping the gluteus maximus and medius (group M) or osteotomy of greater trochanter (group O) on the right hip, as well as combined muscle injury and osteotomy of greater trochanter (group M+O). The gluteus maximus and medius of the operated hips were harvested at days 1, 3, 5, and 10 for isolation of m-progenitors. The cells were cultured in an osteogenic medium for 3 weeks, and osteogenesis was evaluated by matrix mineralization and the expression of osteogenesis-related genes. The expression of type I collagen, RUNX2 (runt-related transcription factor 2), and osteocalcin by the m-progenitors of group M+O was significantly increased, compared with groups M and O. Osteogenic m-progenitors in group O increased the expression of bone morphogenetic protein 2 and also bone morphogenetic protein antagonist differential screening-selected gene aberrative in neuroblastoma. On histology, there was calcium deposition mostly in the muscles of group M+O harvested at day 10. CD56, representing myogenic progenitors, was highly expressed in the m-progenitors isolated from group M (day 10), but m-progenitors of group M+O (day 10) exhibited the highest expression of platelet-derived growth factor receptor α (PDGFR-α), a marker of muscle-derived mesenchymal stem cells (M-MSCs). The expressions of PDGFR-α and RUNX2 were colocalized in osteogenic m-progenitors. The data indicate that the tissue environment simulated in the M+O model is a favorable condition for HO formation. Most likely, M-MSCs, rather than myogenic progenitors, in the m-progenitors participate in HO formation. SIGNIFICANCE/CONCLUSIONS:The prevalence of traumatic heterotopic ossification (HO) is high in war injury. The pathogenesis of HO is still unknown. This study clarified the contribution of a tissue environment created by bone or muscle injury to the formation of HO. The study also found that muscle-derived mesenchymal stem cells, but not myogenic progenitors, are involved in the formation of HO. The findings of this study could be used to strategize the prevention and treatment of HO.

There is no research on the assessment or treatment of help-seeking behaviours for individuals with traumatic brain injury (TBI). This paper describes the development of a protocol, NICE (Noticing you have a problem, Identifying the information you need for help, Compensatory strategies, Evaluating progress) to train help-seeking for adults with TBI when lost. Theoretical and treatment components from three empirically validated interventions that target social problem-solving and communication skills were adapted to develop NICE: the Group Interactive Structured Treatment for Social Competence (GIST), the Problem Solving Group Protocol (PSG) and Interpersonal Recall (IPR). Preliminary pilot data evaluating the efficacy are presented for three adult persons with TBI. All three participants improved on the Executive Function Route Finding Task (EFRT) and help-seeking behaviours when wayfinding. Help-seeking is a constitutive factor in the wayfinding process capable of improvement. Preliminary evidence supports further investigation of this group intervention.

We report a general method for small aggregates (or clusters) of water-borne colloids inside water-in-oil (W/O) emulsions. First, an aqueous suspension of monodisperse polystyrene or silica NOD microspheres was emulsified into polydisperse water droplets on micrometer scales in oil phase and colloidal aggregates were produced spontaneously during slow evaporation of water. Then, the colloidal clusters consolidated by complete removal of water were separated from the oil phase and re-dispersed in water for the subsequent fractionation according to the number (n) of the constituent spheres by a density gradient ultracentrifugation. Each cluster of n particles possessed a unique configuration except for a few particular cases of n = 7, 8, and 11, in which we observed some isomeric structures, depending on their surface properties of colloidal microspheres. These isomers have not been reported in the preceding studies for colloidal clusters fabricated from the phase-inverted oil-in-water emulsions.

In this longitudinal study, quantitative and qualitative changes in responses of people with aphasia were examined on a phonemic fluency task. Eighteen patients were tested at 3-month intervals on the letters F-A-S while they received comprehensive, intensive treatment from 3 to 12 months post-stroke. They returned for a follow-up evaluation at an average of 10 months post-intervention. Mean group scores improved significantly from beginning to end of treatment, but declined post-intervention. Patients produced a significantly greater number and proportion of modifiers (adjectives and adverbs) between the beginning and end of treatment, with no decline afterwards, implying that they had access to a wider range of grammatical categories over time. Moreover, patients used significantly more phonemic clusters in generating word lists by the end of treatment. These gains may be attributed to the combined effects of time since onset and the linguistic and cognitive stimulation that patients received in therapy. LEARNING OUTCOMES: Readers of this paper should (1) gain a better understanding of verbal fluency performance in the assessment of aphasia, (2) recognize the importance of analyzing qualitative aspects of single word production in aphasia, and (3) contribute to their clinical judgment of long term improvement in aphasia.