Effect of strontium on osteoporotic MSCs.
Research type
Research Study
Full title
The effect of strontium on mesenchymal stem cells from osteoporotic donors.
IRAS ID
270177
Contact name
Susan Clarke
Contact email
Sponsor organisation
Queen's University Belfast
Duration of Study in the UK
2 years, 6 months, 1 days
Research summary
Bone fractures often require a fixation device such as a plate or screw to stabilise the bones until healing can occur. In patients with frail bones- osteoporosis- the bone is so poor that the plates and screws (fixators) don't hold. A bit like trying to get a screw to hold in cardboard. Strontium is a metal similar to calcium which has been shown to encourage new bone to form. We plan to put strontium into a 'bioresorbable' fixator, so that new bone is encouraged while the fracture heals but first we need to determine the effect of strontium in vitro.
Bioresorbable polymers (plastic materials that are degraded by the body over time and replaced with normal tissue) have been used to make screws and pins for fracture repair for some time. It is possible to include a "bioactive agent" within these polymers to make them more effective and we have developed a method of treating the surface of the polymer to control release of the "bioactive agent". The questions we would like to answer are:
(1) what is the optimum dose of strontium?
(2) do cells from osteoporotic donors behave the same as those from donors with normal bone?Our experimental plan will test the response of bone cells derived from the bone marrow of osteoporotic and normal donors bone marrow to identify an ideal concentration of strontium.
Lay summary of study results:
For the dose response to Sr study, results there was no increase in cell death in any group. Sr increased cell number in a broadly dose dependent fashion. At d1, cell number was lowest in Gp 2 (Figure 1) and highest in the control group. This difference between groups was lost by d4 and there was no statistically significant difference in cell number between the groups at d4 or d7. ALP activity was increased at lower concentrations of Sr and reduced compared to control at higher Sr concentrations at all time points. In contrast to cell number, the highest amount of ALP activity was found in the OP groups and the lowest in the control suggesting that the cell proliferation stimulated by Sr in the control group delayed differentiation in this group.When investigating the effect of Sr addition to a bioresorbable polymer, all groups in the study supported cell attachment onto the scaffolds. Cell number did not increase with time for control donor cells, but did increase in the osteoporotic donor cells. Cells from osteoporotic donors also showed increased activity in osteoclast cells and decreased bone formation markers compared to controls.
There was a difference between osteoporotic and non-osteoporotic donor bone marrow derived mesenchymal stem cells in cell number and response in both 2D monoculture and in the response to 3D printed bioresorbable polymers. This difference in donor cell response has implications for the wider research field as often responses are investigated using “normal” cells, calling into question the translatability of the research. This research highlights the importance of using condition-specific cells for in vitro screening.
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
19/WM/0274
Date of REC Opinion
4 Oct 2019
REC opinion
Further Information Favourable Opinion