Transplantation of multipotent cells extracted from adult skeletal muscles into the subventricular zone of adult rats

Abstract

Stem cells isolated from adult tissues may be useful for autologous cell therapy in the nervous system. In the present study we tested the ability of multipotent stem cells isolated from adult muscle to survive and respond to migratory and differentiating cues when transplanted into the adult subventricular zone (SVZ). Prior to transplantation the cells were grown as spheres that expressed doublecortin, nestin, and betaIII-tubulin, as well as the mRNAs for the receptor EphA4 and the ligands ephrin B1, ephrin B2, but not ephrin B3. Four weeks after transplantation into the anterior part of the SVZ in adult rats, surviving cells were observed along the ventricular wall, in the SVZ, and in the posterior rostral migratory stream (RMS). None of these cells stained for betaIII-tubulin or doublecortin, which are molecules expressed by migrating neuroblasts, and none were present in the more rostral regions of the RMS or the olfactory bulb. However, most surviving transplanted cells were integrated into the wall of the lateral ventricle and expressed vimentin, a marker also expressed by ependymocytes. No tumors were observed 4 weeks posttransplantation. Our results suggest that multipotent stem cells isolated from adult muscle, which can be easily and safely isolated from patients and rapidly expanded ex vivo, may provide autologous vectors for the local delivery of secreted factors to the ventricles or nearby regions.

Effects of Interleukin-6, Leukemia Inhibitory Factor, and Ciliary Neurotrophic Factor on the Proliferation and Differentiation of Adult Human Myoblasts

“…The myoblasts provide the sufficient source for muscle formation, which is potentially useful for treatment of the muscular atrophy and non-muscle diseases, such as neurodegenerative disorders (Gussoni et al 1992;Mignon et al 2005). Furthermore, these cells can be obtained from the patients per se, providing the advantage for clinical use.…”

Adult-derived stem cells and their potential for use in tissue repair and molecular medicine

“…ic factor acts on germ layer lineage ectodermal stem cells derived from the adult rat to form cells belonging to the ectodermal lineage [4,[24][25][26][27][28]. Bone morphogenetic protein-4 acts on germ layer lineage mesodermal stem cells from either species to form cells belonging to the mesodermal lineage [4,5].…”

“…Germ layer lineage stem cells derived from the adult rat and derived from the adult human respond to any general lineage-induction agent (e.g., dexamethasone) [8] by forming cells belonging to their respective germ layer lineages [4,5]. The germ layer lineage stem cells are responsive to lineage-specific induction agents [3][4][5][24][25][26][27][28]. Thus, brain-derived neurotroph- Table 1 Karyotypic analysis of germ layer lineage mesodermal stem cells…”

“…Rather, germ layer lineage mesodermal stem cells respond to bone morphogenetic protein-4 (which acts on cells of the mesodermal lineage) to form cells of mesodermal origin, e.g., carttilage and bone [3,8,[22][23][24]. When exposed to general and specific inductive agents, germ layer lineage ectodermal stem cells derived from the adult rat or derived from the adult human have differentiated into neuronal progenitor cells, neurons, ganglia, oligodendrocytes, astrocytes, synaptic vesicles, radial glial cells, and keratinocytes [4,5,[24][25][26][27][28]]. When exposed to general and specific inductive agents, germ layer lineage mesodermal stem cells derived from the adult rat or derived from the adult human have differentiated into skeletal muscle, smooth muscle, cardiac muscle, white fat, brown fat, hyaline cartilage, articular cartilage, elastic cartilage, growth plate cartilage, fibrocartilage, endochondral bone, intramembranous bone, tendons, ligaments, dermis, fibrogenic scar tissue, endothelial cells, erythrocytes, lymphocytes, and macrophages [4,22,23].…”

“…Cells with characteristics similar to those described above for germ layer lineage mesodermal stem cells have also been isolated from the skeletal muscle of mice, rabbits, dogs, goats, sheep, and pigs [1,4], from the dermis of mice and rats [1,4], from the connective tissue layers surrounding the myocardium of mice and rats [1,4], from granulation tissue derived from rabbits and humans [1,4], and from other tissue sites, including brain, bone marrow, breast, blood, and the connective tissues associated with bone, cartilage, fat, nerves, and organs of the respiratory system, gastrointestinal system, and urinary system [1][2][3][4][5][29][30][31][32][33][34][35][36]. Germ layer lineage ectodermal stem cells have been isolated from meninges, brain tissues, skeletal muscle, dermis, fat, and skin [2,[24][25][26][27][28]. And germ layer lineage endodermal stem cells have been isolated from dermis, liver, pancreas, and skeletal muscle [2,4,5,37,38].…”