Mesenchymal Stromal Cells (MSC) have been proposed as a potential therapy for a broad range of diseases including those affecting the musculoskeletal system. MSCs have received market authorization for treatment of graft versus host disease and fistulizing Crohn's disease. In addition, there are clinical trials underway for diseases affecting all organ systems. GMP manufactured cells are required for these clinical trials and suitable facilities with regulatory approval are thus crucial for the translational process. In this presentation I will review the process whereby such a facility has been constructed at NUI Galway and discuss challenges in operations and sustainability. Researchers at REMEDI and spin out company Orbsen Therapeutics are currently involved in 7 clinical trials using MSCs, 4 of which are EU wide consortia funded by the EU Commission. The presentation will also discuss issues such as source of MSCs, cell sorting, use of bioreactors and xeno-free processes.

Recent studies have shown that bone mineral distribution is more heterogeneous in bone tissue from an animal model of osteoporosis and osteoporotic human vertebral trabeculae. These tissue alterations may play a role in bone fragility seen in osteoporosis, albeit that they are not detectable by current diagnostic techniques (dual-energy X-ray absorptiometry, DXA). Type II Diabetes Mellitus (T2DM) also increases a patient's fracture risk beyond what can be explained or diagnosed by DXA, and is associated with impaired bone cell function, compromised collagen structure and reduced mechanical properties. However, it is not currently known whether osteoporosis or T2DM leads to an increased mineral heterogeneity in the femoral head of humans, a common osteoporotic fracture site. In this study, we examine bone microarchitecture, mineralisation and mechanical properties of trabecular bone from osteoarthritic, diabetic and osteoporotic patients. We report that while osteoporotic trabecular bone has significantly deteriorated mechanical properties and microarchitecture compared to the other groups, there is also a significant increase in mean mineral content. Moreover, the heterogeneity of the mineral content in osteoporotic bone is significantly higher than osteoarthritic (+35%) and diabetic (+13%) groups. We propose that the compromised architecture following bone loss at the onset of osteoporosis alters the mechanical environment, which initiates compensatory changes in mineral content. We show for the first time that trabecular bone mineralisation is significantly more heterogeneous (+20%) in T2DM compared to osteoarthritic controls. Interestingly, bone microarchitecture and mechanical properties are not significantly different between diabetic and osteoarthritic groups despite this increase in mineral heterogeneity.

Patients living with type 1 diabetes mellitus (T1DM) can develop early onset osteoporosis and are exposed to an increased risk of fracture. Skeletal health can be influenced easily with diet and exercise. However, diabetes mellitus (DM)-related osteopathy is not emphasized in the public information campaigns on the American Diabetes Association, Diabetes UK, Diabetes Ireland or International Diabetes Federation websites. This investigation aims to assess the perceptions of patients regarding living with T1DM and their baseline knowledge on DM-related osteopathy. A survey was administered to 102 consenting individuals living with T1DM in attendance at the Galway University Hospital Diabetes Centre. Of the respondents, 44% were female and 56% male (mean age of 43). Respondents had T1DM for a mean of 21 years. Participants were asked to identify DM-related complications, including bone thinning and bone fractures. Respondents were primarily concerned about developing DM-related blindness, kidney damage and amputations, but not osteopathy. 49% of respondents did not identify osteopathy as a potential DM-related complication, 28% of respondents related DM with bone thinning and bone fractures, and 22% individuals only identified bone thinning or bone fractures. When asked for their primary source of DM-related information, endocrinologists and internet where identified. When comparable questions were asked of DM-related healthcare professionals, 56% did not recognize osteopathy as a complication of T1DM. This study demonstrated a low-level awareness of the impact living with T1DM has on bone health. The deployment of patient-interactive activities or educational modules may enhance the future health of individuals living with T1DM.

Macromolecular crowding (MMC) is a biophysical phenomenon that accelerates thermodynamic activities and biological processes by several orders of magnitude. Herein, we ventured to identify the optimal crowder and to assess the influence of MMC in umbilical cord mesenchymal stem cell. 7 types of carrageenan (κ&λ, κ-LV1, κ-LV2, λ-MV, λ-HV, ι-MV, ι-HV) acted as crowder and biophysical properties were assessed respectively. Human umbilical cord mesenchymal stem cells were seeded at 15,000 cells/cm² in 24 well plates and allowed to attach for 24 h. Subsequently, the medium was changed to medium with 7 types of carrageenan (10, 50, 100, 500 μg/ml) and 100 μM L-ascorbic acid phosphate (Sigma Aldrich). Medium without carrageenan was used as control. Cell morphology and SDS-PAGE analysis were conducted after 3, 5 and 7 days. Biophysical assessment showed 7 types of carrageenan have increased particle size with concentration, good polydispersity and negative charges. SDS-PAGE and densitometric analyses revealed significant increase (p < 0.001) in collagen deposition in the presence of 10 μg/ml carrageenan λ and ι at all the time points. SDS-PAGE and densitometric analysis also showed that the highest collagen deposition was observed in culture at 50 μg/ml carrageenan λ. No significant difference was observed in cell morphology between the groups. Collectively, these data primarily illustrate the beneficial effect of carrageenan λ in human umbilical cord mesenchymal stem cell culture.

Background

70% of Breast Cancer patients develop metastatic bone deposits, predominantly spinal metasases. Adult Mesenchymal Stem Cells (MSCs) are multiprogenitor stem cells found within the bone marow which have the ability to self renew and differentiate into multiple cell types. MSCs home specifically to tumour sites, highlighting their potential as delivery vehicles for therapeutic agents. However studies show they may also increase tumour metastatic potential.

We performed a randomised double-blind controlled study in patients undergoing elective knee arthroscopy to assess the effect of intra-articular morphine on postoperative pain relief. Patients in the study group (n = 10) received 5 mg of morphine in a 25 ml dilution intra-articularly while those in the control group (n = 10) received 25 ml of saline. Postoperative pain was assessed at intervals by a visual analogue scale and the requirement for supplementary analgesia was recorded. Those in the study group had significantly lower pain scores and required less systemic analgesics than those in the control group. Plasma profiles for morphine and its metabolites were assayed and showed that they were too low to produce effective analgesia. Evidence suggests that analgesia was mediated by local action within the joint.

The transiliac method of leg lengthening uses a modification of Salter's innominate osteotomy. The bone graft increases the length of the hemipelvis distal to the sacro-iliac joint. Leg-length inequality in 23 patients was treated by this method with an average gain in length of 2.8 cm (2.0 to 3.5). Apart from one residual femoral nerve palsy there were no notable complications. The facility to redirect the acetabulum allowed by the technique, may be useful in cases of potential hip instability or acetabular dysplasia.

A Salter innominate osteotomy is used to treat acetabular dysplasia, but reports of its effects on the position of the femoral head are few and conflicting. Lateral shift would increase the resultant forces acting on the joint and be detrimental. We studied 15 Salter innominate osteotomies and demonstrated that a correctly performed osteotomy does not significantly alter the distance from the centre of the femoral head to the midline of the body. Stereophotogrammetry was used in three patients to delineate the axis of rotation of the distal acetabular fragment and determine the locus of movement of the centre of the femoral head about it. Our results explain why the Salter osteotomy does not lateralise the femoral head.

We reviewed 26 fractures involving the distal physis of the tibia to identify the patterns of formation and displacement of the subsequent growth disturbance lines. Twenty-one patients showed a regular "normal" pattern of line and healed with no deformity. Three patients had medical physeal arrest revealed by abnormal lines. Two other cases had a minor central physeal arrest without subsequent deformity. The pattern and character of the growth disturbance line can provide an early warning of potential deformity.

Hip rotation in extension and flexion was studied in 23 patients with idiopathic intoeing gait. In extension all the hips had markedly increased medial rotation and limited lateral rotation, fulfilling the criteria of excessive femoral anteversion. In flexion, however, rotation varied widely; in one group of patients medial rotation remained greater than lateral, but in the second group lateral rotation was equal to or greater than medial. CT scans showed that the hips in the first group were significantly more anteverted than those in the second. Clearly measurement of hip rotation in extension alone does not provide a dependable indication of femoral anteversion in children with intoeing gait; rotation in flexion also needs to be measured.

Seventy-seven children admitted with a provisional diagnosis of acute osteomyelitis over a three year period have been reviewed. Acute haematogenous osteomyelitis was confirmed in 45 of these patients whose ages varied from three days to 14 years with a mean of 6.2 years. All patients were treated with intravenous fusidic acid and cloxacillin with splintage for three weeks followed by oral antibiotics for a further period of six weeks. Only seven patients required operation. One patient had recurrence of infection; all other patients were cured with no evidence of chronic osteomyelitis. It is suggested that surgical drainage of acute haematogenous osteomyelitis is seldom needed and that high intravenous doses of antibiotics in combination with splintage are adequate treatment in most cases.