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.