Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation

Abstract

The effects of bone marrow stromal cells (BMSCs) on the repair of injured spinal cord and on the behavioral improvement were studied in the rat. The spinal cord was injured by contusion using a weight-drop at the level of T8-9, and the BMSCs from the bone marrow of the same strain were infused into the cerebrospinal fluid (CSF) through the 4th ventricle. BMSCs were conveyed through the CSF to the spinal cord, where most BMSCs attached to the spinal surface although a few invaded the lesion. The BBB score was higher, and the cavity volume was smaller in the rats with transplantation than in the control rats. Transplanted cells gradually decreased in number and disappeared from the spinal cord 3 weeks after injection. The medium supplemented by CSF (250 microl in 3 ml medium) harvested from the rats in which BMSCs had been injected 2 days previously promoted the neurosphere cells to adhere to the culture dish and to spread into the periphery. These results suggest that BMSCs can exert effects by producing some trophic factors into the CSF or by contacting with host spinal tissues on the reduction of cavities and on the improvement of behavioral function in the rat. Considering that BMSCs can be used for autologous transplantation, and that the CSF infusion of transplants imposes a minimal burden on patients, the results of the present study are important and promising for the clinical use of BMSCs in spinal cord injury treatment.

Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

“…Also, there was no expression of any neuronal antigens by either cultured or transplanted BMSC, supporting the findings of most other studies. 14,16,21 In contrast, some reports suggest that BMSC express neuronal markers either in vitro or after transplantation into the injured spinal cord. 22,23 Indeed, our LP transplanted BMSC did not express any neural antigens and showed high levels of fibronectin expression as in culture.…”

“…We also examined LP transplantation of rat BMSC, which have been shown to home to sites of injury. 2,14 Materials and methods…”

Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury

“…administration of MSCs for spinal cord repair. Ohta et al 83 examined MSCs infused into rat cerebrospinal fluid (CSF) through the fourth ventricle after T8-9 contusion MSCs were found in the lesion cavity and improved functional recovery but to a much greater extent in the intra-lesional group injury, and found that they promoted functional recovery and reduced cavity formation at the injury site. Lumbar puncture delivery of adult rat MSCs into spinal cordinjured rats resulted in reduced cavitation, which was maximal when cells were transplanted within 14 days of injury.…”

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

“…It must not be overlooked that the transplantation of any cell may confer benefits over saline or media injections, and this is rarely controlled for by using additional cell types as controls (e.g., fibroblasts). In most studies, the cells were injected directly into or next to the SCI site, yet, in some hands, intrathecal (Ohta et al, 2004) and even intravenous (Urdzikova et al, 2006) delivery seems successful. Other researchers did not have success with intravenous delivery (Fan et al, 2008).…”