Untitled

Abstract

The development of cell or gene therapies for diseases involving cells that are widely distributed throughout the body has been severely hampered by the inability to achieve the disseminated delivery of cells or genes to the affected tissues or organ. Here we report the results of bone marrow transplantation studies in the mdx mouse, an animal model of Duchenne's muscular dystrophy, which indicate that the intravenous injection of either normal haematopoietic stem cells or a novel population of muscle-derived stem cells into irradiated animals results in the reconstitution of the haematopoietic compartment of the transplanted recipients, the incorporation of donor-derived nuclei into muscle, and the partial restoration of dystrophin expression in the affected muscle. These results suggest that the transplantation of different stem cell populations, using the procedures of bone marrow transplantation, might provide an unanticipated avenue for treating muscular dystrophy as well as other diseases where the systemic delivery of therapeutic cells to sites throughout the body is critical. Our studies also suggest that the inherent developmental potential of stem cells isolated from diverse tissues or organs may be more similar than previously anticipated.

Role of VEGF-A in Pancreatic Beta Cells

“…Several studies have indicated that bone marrow (BM)-derived cells have the capacity to differentiate into various cell types through a process termed transdifferentiation [26][27][28][29][30][31][32][33]. However, these data are controversial, because several other studies reported that these cells fail to show such transdifferentiation [34][35][36][37][38][39].…”

Bone Marrow Contributes Simultaneously to Different Neural Types in the Central Nervous System through Different Mechanisms of Plasticity

“…Thus, the contribution of BMDC to diverse tissues has been described under normal and In recent years, it has been shown that bone marrowderived cells (BMDC) owe their plasticity to changes in pathological conditions. The contribution rate was always very scarce (2,42), but this low "basal" frequency, their fate, which allows their contribution to different cell populations in diverse organs (7,19,22,26,40,41,48), described under physiological conditions, was significantly increased when the target organs underwent inincluding the central nervous system (CNS) (2, 8,9,34,54). This surprising capacity has been considered a pojury (2,27,34,56), especially when accompanied by inflammation (23,38).…”

Molecular signatures define myogenic stem cell populations

“…This method, which relies on the differential ability of stem cells to efflux the Hoechst dye, defines a rare population of stem cells that can adopt alternative fates in permissive environments (19,20). For example, these adult stem cells (identified using FACS and based on their ability to efflux Hoechst 33342 dye) have been shown to repopulate mutant (i.e., mdx or dystrophin deficient skeletal muscle) or injured adult skeletal muscle (19). Studies undertaken in the Sorrentino laboratory (St. Jude Children's Research Hospital, Memphis, TN) and our laboratory (UT Southwestern Dallas, TX) have established that the ability of adult stem cells to efflux Hoechst 33342 dye is dependent on the expression of Abcg2, which is a member of the family of ATP binding cassette (ABC) transporters (21,22).…”

“…This SP cell population is identified using Hoechst 33342 dye and dual wavelength flow cytometry as these cells are able to efflux the Hoechst dye (17,18). This method, which relies on the differential ability of stem cells to efflux the Hoechst dye, defines a rare population of stem cells that can adopt alternative fates in permissive environments (19,20). For example, these adult stem cells (identified using FACS and based on their ability to efflux Hoechst 33342 dye) have been shown to repopulate mutant (i.e., mdx or dystrophin deficient skeletal muscle) or injured adult skeletal muscle (19).…”