Stem cell based intervertebral disc (IVD) regeneration is quickly moving towards clinical applications. However, many aspects need to be investigated to routinely translate this therapy to clinical applications, in particular, the most efficient way to deliver cell to the IVD. Cells are commonly delivered to the IVD through the annulus fibrosus (AF) injection. However, recent studies have shown serious drawbacks of this approach. As an alternative we have described and tested a new surgical approach to the IVD via the endplate-pedicles (transpedicular approach). The Purpose of the study was to test MSCs/hydrogel transplantation for IVD regeneration in a grade IV preclinical model of IDD on large size animals via the transpeducular approach with cell dose escalation. Adult sheep (n=18) underwent bone marrow aspiration for autologous MSC isolation and expansion. MSC were suspended in autologous PRP and conjugated with Hyaluronic Acid and Batroxobin at the time of transplant (MSCs/hydrogel). Nucleotomy was performed via the transpedicular approach in four lumbar IVDs and that were injected with 1) hydrogel, 2) Low doses of MSC/hydrogel, 3) High doses of MSC/hydrogel, 4) no injection (CTRL). The endplate tunnel was sealed using a polyurethane scaffold. X-ray and MRI were performed at baseline and 1,3,6,12 months. Disc macro- and micro-morphology were analysed at each time point.Background
Methods
For the treatment of ununited fractures, we developed
a system of delivering magnetic labelled mesenchymal stromal cells
(MSCs) using an extracorporeal magnetic device. In this study, we
transplanted ferucarbotran-labelled and luciferase-positive bone
marrow-derived MSCs into a non-healing femoral fracture rat model
in the presence of a magnetic field. The biological fate of the
transplanted MSCs was observed using luciferase-based bioluminescence
imaging and we found that the number of MSC derived photons increased
from day one to day three and thereafter decreased over time. The
magnetic cell delivery system induced the accumulation of photons at
the fracture site, while also retaining higher photon intensity
from day three to week four. Furthermore, radiological and histological
findings suggested improved callus formation and endochondral ossification.
We therefore believe that this delivery system may be a promising
option for bone regeneration.
In order to ensure safety of the cell-based therapy for bone
regeneration, we examined BM cells obtained from a total of 13 Sprague-Dawley (SD) green
fluorescent protein transgenic (GFP-Tg) rats were culture-expanded
in an osteogenic differentiation medium for three weeks. Osteoblast-like
cells were then locally transplanted with collagen scaffolds to
the rat model of segmental bone defect. Donor cells were also intravenously infused
to the normal Sprague-Dawley (SD) rats for systemic biodistribution.
The flow cytometric and histological analyses were performed for
cellular tracking after transplantation.Objectives
Methods
