Isolation and transplantation of multipotential populations of epidermal growth factor-responsive, neural progenitor cells from the canine brain

Abstract

Glial cell transplantation into myelin-deficient rodent models has resulted in myelination of axons and restoration of conduction velocity. The shaking (sh) pup canine myelin mutant is a useful model in which to test the ability to repair human myelin diseases, but as in humans, the canine donor supply for allografting is limited. A solution may be provided by self-renewing epidermal growth factor (EGF)-responsive multipotential neural progenitor cell populations ("neurospheres"). Nonadherent spherical clusters, similar in appearance to murine neurospheres, have been obtained from the brain of perinatal wildtype (wt) canine brain and expanded in vitro in the presence of EGF for at least 6 months. Most of the cells in these clusters express a nestin-related protein. Within 1-2 weeks after removal of EGF, cells from the clusters generate neurons, astrocytes, and both oligodendroglial progenitors and oligodendrocytes. Transplantation of lacZ-expressing wt neurospheres into the myelin-deficient (md) rat showed that a proportion of the cells differentiated into oligodendrocytes and produced myelin. In addition, cells from the neurosphere populations survived at least 6 weeks after grafting into a 14-day postnatal sh pup recipient and at least 2 weeks after grafting into an adult sh pup recipient. Thus, neurospheres provide a new source of allogeneic donor cells for transplantation studies in this mutant.

Regeneration and repair in multiple sclerosis: The view of experimental pathology

“…The spinal cord of the taiep rat undergoes progressive myelin loss so that by 12 months of age large numbers of axons lack myelin sheaths and there is a significant astrocytosis [16]. Unlike the situation that follows transplantation of OPCs into the neonatal myelin deficient rat [17] and the neonatal shiverer mouse [18] where extensive myelination results, transplantation of myelination competent OPC into the spinal cord of the adult taiep rat results in only a very small area of myelin sheath formation [19]. One reason for this poor result is failure of the transplanted OPCs to populate the already OPC-populated tissue, since if one removes the endogenous OPCs with 40 Gy of X-irradiation extensive spread of transplanted OPCs is achieved.…”

Serum-Free Spheroid Culture of Mouse Corneal Keratocytes

“…[37][38][39] In our study, the sphere culture of keratocytes did not require serum, and the dendritic keratocyte phenotype was restored when subcultured on plastic substrate in serum-free medium.…”

Spontaneous differentiation of porcine neural progenitors in vitro

“…Neural progenitor cells (NPCs) have now been derived from the brain or spinal cord of mammalian species, including mouse (Vukicevic et al 2010;Lindstrom et al 2009;Hernandez-Benitez et al 2010), dog (Walton and Wolfe 2008;Milward et al 1997), rat (Go et al 2009), human (Luo et al 2010;Liu et al 2010) and pig (Schwartz et al 2005). PNPCs seems to be less immunogenic and thus survive better than porcine neural xenografts (Armstrong et al 2001;Barker et al 2000), up to 5 months in rats (Harrower et al 2006).…”