Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons

Abstract

The potential of bone marrow cells to differentiate into myelin-forming cells and to repair the demyelinated rat spinal cord in vivo was studied using cell transplantation techniques. The dorsal funiculus of the spinal cord was demyelinated by x-irradiation treatment, followed by microinjection of ethidium bromide. Suspensions of a bone marrow cell fraction acutely isolated from femoral bones in LacZ transgenic mice were prepared by centrifugation on a density gradient (Ficoll-Paque) to remove erythrocytes, platelets, and debris. The isolated cell fraction contained hematopoietic and nonhematopoietic stem and precursor cells and lymphocytes. The cells were transplanted into the demyelinated dorsal column lesions of immunosuppressed rats. An intense blue beta-galactosidase reaction was observed in the transplantation zone. The genetically labeled bone marrow cells remyelinated the spinal cord with predominately a peripheral pattern of myelination reminiscent of Schwann cell myelination. Transplantation of CD34(+) hematopoietic stem cells survived in the lesion, but did not form myelin. These results indicate that bone marrow cells can differentiate in vivo into myelin-forming cells and repair demyelinated CNS.

Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord

“…We did not characterize these myelinated axons as oligodendrocyte-like or Schwann cell-like by immunostaining in this study. However, previous work has demonstrated both patterns of myelination by bone marrow cell transplantation (Sasaki et al, 2001;Akiyama et al, 2002a, b).…”

“…Transplantation of an acutely isolated bone marrow mononuclear cell fraction by either direct intraspinal microinjection (Sasaki et al, 2001) or intravenous delivery (Akiyama et al, 2002a) into the demyelinated rat spinal cord results in relatively extensive remyelination. Plastic-adherent cells from bone marrow are referred to as stromal cells (Friedenstein, 1976) and are thought to contain nonhematopoietic stem cells that can differentiate along multiple mesenchymal cell lineages (Prockop, 1997).…”

“…Plastic-adherent cells from bone marrow are referred to as stromal cells (Friedenstein, 1976) and are thought to contain nonhematopoietic stem cells that can differentiate along multiple mesenchymal cell lineages (Prockop, 1997). The mononuclear cell fraction of bone marrow can be readily isolated by density gradient and contains stromal cells, hematopoietic and nonhematopoietic stem and precursor cells, and lymphocytes (Azizi et al, 1998;Phinney et al, 1999;Sasaki et al, 2001;Akiyama et al, 2002a). Transplantation of GFP-expressing mouse stromal cells by direct microinjection into the immunosuppressed rat indicates that these cells can form myelin in the demyelinated spinal cord (Akiyama et al, 2002b).…”

Remyelination of the spinal cord following intravenous delivery of bone marrow cells

“…Moreover, systemic delivery of bone marrow cells has been shown to enhance functional recovery in rodents following contusive spinal cord injury (Chopp et al, 2000) and middle cerebral artery infarction (Chen et al, 2001). When directly injected into the demyelinated rat spinal cord, isolated marrow cells derived from the mononuclear layer remyelinate these axons (Sasaki et al, 2001). These studies raise the intriguing possibility that bone marrow cells could be delivered intravenously to achieve repair of demyelinated axons.…”

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

“…Stem-like cells, derived from bone marrow, have been reported to myelinate spinal axons when introduced at the site of focal demyelination. 324,325 Intriguingly, these cells also stimulated remyelination -and themselves formed myelinwhen injected into the bloodstream. 325,326 If such cells can reliably overcome the blood-brain barrier, migrate to demyelinated CNS regions and differentiate appropriately, with their proliferation being controlled, then an intravenous delivery route presents an attractive alternative to direct parenchymal injection into the damaged CNS.…”