Cells exhibiting neuronal cell progenitor characteristics and methods of making them
Disclosed are cells exhibiting neuronal progenitor cell characteristics, and methods of making them from marrow adherent stem cells by regulating cellular pathways in the marrow adherent stem cells that are associated with glial transdifferentiation of the marrow adherent stem cells.
1 . A method of producing cells exhibiting neuronal progenitor cell characteristics from material comprising marrow adherent stem cells, the method comprising:
regulating cellular pathways in the marrow adherent stem cells that are associated with glial transdifferentiation of the marrow adherent stem cells;
wherein the cellular pathways are sufficiently regulated to induce at least a portion of the marrow adherent stem cells to transdifferentiate into cells exhibiting neuronal progenitor cell characteristics; and
with the proviso that the regulating does not comprise transfection of the marrow adherent stem cells with notch intracellular domain.
2 . The method of claim 1 , wherein the marrow adherent stem cells are selected from the group consisting of human marrow adherent stem cells, rat marrow adherent stem cells, mouse marrow adherent stem cells, primate marrow adherent stem cells, pig marrow adherent stem cells, cow marrow adherent stem cells, and sheep marrow adherent stem cells.
3 . The method of claim 1 , wherein the regulating comprises incubation of a glial regulating agent with the marrow adherent stem cells.
4 . The method of claim 3 , wherein the incubation comprises transfection of a glial regulating agent into the marrow adherent stem cells.
5 . The method of claim 3 , wherein the glial regulating agent comprises inhibitors or antagonists or agents that interfere with signaling pathways for gliogenic factors.
6 . The method of claim 3 , wherein the glial regulating agent comprises agonists for neurogenesis.
7 . The method of claim 3 , wherein the glial regulating agent comprises a JAK/STAT inhibitor; an inhibitor of STAT1 or STAT3; 4-(4′-hydroxyphenyl)amino-6,7-dimethoxyquinazoline; antagonists of bone morphogenic protein 2 or bone morphogenic protein; whole or portions of gene products from genes expressing Noggin, Chordin, Follistatin, sonic hedgehog (SHH), or agonists of these genes; Hes inhibitors; Hes 1 or Hes 5 inhibitors; inhibitors of Id-1; inhibitors of mammalian homologs of Drosophila glide/gcm; inhibitors of Sox9; inhibitors of Neurogenin3; inhibitors of CNTF; whole or portions of gene products from genes expressing Wnt1, Neurogenin1, Mash1, Math1, Math6, or NeuroD, or their agonists.
8 . The method of claim 1 , further comprising:
isolating the cells exhibiting neuronal progenitor cell characteristics; and
administering them to a patient.
9 . The method of claim 1 , wherein the marrow adherent stem cells are derived from cord blood.
10 . The method of claim 1 , wherein the marrow adherent stem cells are derived from bone marrow.
11 . A method for producing cells exhibiting neuronal progenitor cell characteristics comprising:
incubating marrow adherent stem cells with a glial regulating agent in an amount sufficient to induce at least a portion of the marrow adherent stem cells to transdifferentiate into cells exhibiting neuronal progenitor cell characteristics;
with the proviso that the interacting does not comprise transfection of the marrow adherent stem cells with notch intracellular domain.
12 . The method of claim 11 , wherein the marrow adherent stem cells are selected from the group consisting of human marrow adherent stem cells, rat marrow adherent stem cells, mouse marrow adherent stem cells, primate marrow adherent stem cells, pig marrow adherent stem cells, cow marrow adherent stem cells, and sheep marrow adherent stem cells.
13 . The method of claim 11 , wherein the incubation comprises transfection of the glial regulating agent into the marrow adherent stem cells.
14 . The method of claim 11 , wherein the glial regulating agent comprises inhibitors or antagonists or agents that interfere with signaling pathways for gliogenic factors.
15 . The method of claim 11 , wherein the glial regulating agent comprises agonists for neurogenesis.
16 . The method of claim 11 , wherein the glial regulating agent comprises a JAK/STAT inhibitor; an inhibitor of STAT1 or STAT3; 4-(4′-hydroxyphenyl)amino-6,7-dimethoxyquinazoline; antagonists of bone morphogenic protein 2 or bone morphogenic protein; whole or portions of gene products from genes expressing Noggin, Chordin, Follistatin, sonic hedgehog (SHH), or agonists of these genes; Hes inhibitors; Hes 1 or Hes 5 inhibitors; inhibitors of Id-1; inhibitors of mammalian homologs of Drosophila glide/gcm; inhibitors of Sox9; inhibitors of Neurogenin3; inhibitors of CNTF; whole or portions of gene products from genes expressing Wnt1, Neurogenin1, Mash1, Math1, Math6, or NeuroD, or their agonists.
17 . The method of claim 11 , further comprising:
isolating the cells exhibiting neuronal progenitor cell characteristics; and
administering them to a patient.
18 . The method of claim 11 , wherein the marrow adherent stem cells are derived from cord blood.
19 . The method of claim 11 , wherein the marrow adherent stem cells are derived from bone marrow.
20 . Cells exhibiting neuronal progenitor cell characteristics made according to the method of claim 1 .
21 . Cells exhibiting neuronal progenitor cell characteristics made according to the method of claim 11 .
22 . A method comprising:
administering the cells exhibiting neuronal progenitor cell characteristics of claim 20 to a patient.
23 . A method comprising:
administering the cells exhibiting neuronal progenitor cell characteristics of claim 21 to a patient.
24 . A method comprising:
providing the cells exhibiting neuronal progenitor cell characteristics of claim 1; and
combining the cells exhibiting neuronal progenitor cell characteristics with at least one neurotrophic factor, wherein the at least one neurotrophic factor is present in an amount effective to promote the differentiation of the cells exhibiting neuronal progenitor cell characteristics into cells that exhibit one or more characteristics of neurons.
25 . The method of claim 24 , further comprising:
isolating the cells that exhibit one or more characteristics of neurons.
26 . The method of claim 24 , wherein the at least one neurotrophic factor comprises basic-fibroblast growth factor, ciliary neurotrophic factor, or forskolin.
27 . Cells that exhibit one or more characteristics of neurons produced according to the method of claim 24 .
28 . A method comprising:
administering the cells that exhibit one or more characteristics of neurons of claim 24 to a patient.
29 . A method comprising:
providing the cells exhibiting neuronal progenitor cell characteristics of claim 11; and
combining the cells exhibiting neuronal progenitor cell characteristics with at least one neurotrophic factor, wherein the at least one neurotrophic factor is present in an amount effective to promote the differentiation of the cells exhibiting neuronal progenitor cell characteristics into cells that exhibit one or more characteristics of neurons.
30 . The method of claim 29 , further comprising:
isolating the cells that exhibit one or more characteristics of neurons.
31 . The method of claim 29 , wherein the at least one neurotrophic factor comprises basic-fibroblast growth factor, ciliary neurotrophic factor, or forskolin.
32 . Cells that exhibit one or more characteristics of neurons produced according to the method of claim 29 .
33 . A method comprising:
administering the cells that exhibit one or more characteristics of neurons of claim 29 to a patient.