Transplantation of Bone Marrow Stem Cells as well as Mobilization by Granulocyte-Colony Stimulating Factor Promotes Recovery after Spinal Cord Injury in Rats

Abstract

Emerging clinical studies of treating brain and spinal cord injury (SCI) with autologous adult stem cells led us to compare the effect of an intravenous injection of mesenchymal stem cells (MSCs), an injection of a freshly prepared mononuclear fraction of bone marrow cells (BMCs) or bone marrow cell mobilization induced by granulocyte colony stimulating factor (G-CSF) in rats with a balloon- induced spinal cord compression lesion. MSCs were isolated from rat bone marrow by their adherence to plastic, labeled with iron-oxide nanoparticles and expanded in vitro. Seven days after injury, rats received an intravenous injection of MSCs or BMCs or a subcutaneous injection of GCSF (from day 7 to 11 post-injury). Functional status was assessed weekly for 5 weeks after SCI, using the Basso-Beattie-Bresnehan (BBB) locomotor rating score and the plantar test. Animals with SCI treated with MSCs, BMCs, or G-CSF had higher BBB scores and better recovery of hind limb sensitivity than controls injected with saline. Morphometric measurements showed an increase in the spared white matter. MR images of the spinal cords were taken ex vivo 5 weeks after SCI using a Bruker 4.7-T spectrometer. The lesions populated by grafted MSCs appeared as dark hypointense areas. Histology confirmed a large number of iron-containing and PKH 26-positive cells in the lesion site. We conclude that treatment with three different bone marrow cell populations had a positive effect on behavioral outcome and histopathological assessment after SCI, which was most pronounced after MSC injection.

Migration, fate and in vivo imaging of adult stem cells in the CNS

“…MSCs can be mobilized from the marrow or can be expanded in culture and delivered to the damaged site by direct or systemic injection. 22 Once at the site of injury, MSCs produce factors that inhibit scarring and apoptosis, promote angiogenesis and stimulate host progenitors to divide and differentiate in order to repair the injured tissue. In this regard, the trophic effects of MSCs may have important clinical use.…”

“…A suitable contrast agent for labeling rat or human MSCs, embryonic stem cells and olfactory ensheathing cells is a commercially available contrast agent based on dextran-coated SPIO nanoparticles, Endorem s (Guerbet, France). 22,33,34 Endorem can be easily incorporated by endocytosis, and its uptake does not need to be facilitated by a transfection agent, which can damage large numbers of cells. 35 On the day that nanoparticles were withdrawn, the efficiency of both rat or human MSC labeling (i.e., how many cells out of the total number of analyzed cells were labeled) was 50-70%.…”

“…G-CSF is a growth factor that mobilizes endogenous BMCs containing mainly hematopoietic stem cells, but also progenitor cells and lymphocytes. 22 Rat MSCs labeled with Endorem were injected intravenously into the femoral vein 1 week after lesioning. 22 MR images were taken ex vivo 4 weeks after implantation using a standard whole body resonator.…”

“…22 Rat MSCs labeled with Endorem were injected intravenously into the femoral vein 1 week after lesioning. 22 MR images were taken ex vivo 4 weeks after implantation using a standard whole body resonator. Functional status was assessed weekly for 5 weeks after spinal cord lesioning, using the Basso-Beattie-Bresnahan (BBB) locomotor rating score and the plantar test.…”

Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats

“…The implantation of this bridging hydrogel alone may not have an effect on behavioral improvement in association with scaffold implantation such as has been found in association with stem cells or neurotrophic factors implantation 23,[30][31][32] . Furthermore, a comparative study of four methacrylate hydrogels indicated that the HEMA-MOETACl hydrogel was the best carrier of mesenchymal stem cells (MSCs) in vitro and in vivo 29 .…”