Bone marrow-derived neuronal cells

• US 20060194316A1
• Filed: 01/27/2003
• Published: 08/31/2006
• Est. Priority Date: 05/07/1998
• Status: Abandoned Application

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Sanberg, Paul, Freeman, Thomas, Sanchez-Ramos, Juan, Janssen, William, Song, Shijie
• Application Number:
  US10/353,742
• Publication Number:
  US 20060194316A1
• Time in Patent Office: Days
• US Class Current: 435/368
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2500/46 Amines, e.g. putrescine
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/13 Nerve growth factor [NGF]; Brain-derived neurotrophic factor [BDNF]; Cilliary neurotrophic factor [CNTF]; Glial-derived neurotrophic factor [GDNF]; Neurotrophins [NT]; Neuregulins
• CPC Class Codes: C12N 2501/385 of the family of the retinoic acid recptor, e.g. RAR, RXR; Peroxisome proliferator-activated receptor [PPAR]
• CPC Class Codes: C12N 2501/392 Sexual steroids
• CPC Class Codes: C12N 2502/08 cells of the nervous system
• CPC Class Codes: C12N 2506/1353 from bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0619 Neurons

Abstract

Bone marrow stromal cells (BMSC) differentiate into neuron-like phenotypes in vitro and in vivo, engrafted into normal or denervated rat striatum. The BMSC did not remain localized to the site of the graft, but migrated throughout the brain and integrated into specific brain regions in various architectonic patterns. The most orderly integration of BMSC was in the laminar distribution of cerebellar Purkinje cells, where the BMSC-derived cells took on the Purkinje phenotype. The BMSC exhibited site-dependent differentiation and expressed several neuronal markers including neuron-specific nuclear protein, tyrosine hydroxylase and calbindin. BMSC can be used to target specific brain nuclei in strategies of neural repair and gene therapy.

Claims

1. Non-fetal, non-tumorigenic, bone-marrow derived neuronal cells.

2. The cells of claim 1, further comprising being capable of migrating.

3. A cell line of neuronal cells arising from bone marrow stromal cells having been incubated with retinoic acid A for a time sufficient to modify at least a portion to neuronal cells, wherein the neuronal cells have the ability to migrate and localize to specific neuroanatomical regions where the Neuronal cells differentiate into neurons typical of the region and integrate in characteristic architectonic patterns.

5. A method of treating a neurodegenerative disorder comprising administering a sufficient quantity of the cells produced by claim 3 to an individual with said neurodegenerative disorder.

6. The method of claim 5, wherein the disorder is Parkinson'"'"'s Disease, Alzheimer'"'"'s disease, ischemia, spinal cord damage, ataxia, or alcoholism.

4. A kit for neuronal cell auto-transplant comprising

a) a syringe suitable for obtaining bone marrow

b) plastic flask with dehydrated culture medium;

c) bone marrow stem cell.

7. A method of screening for effects of substances on human neuronal cells, said method comprising

a) providing a mammal with implanted human neuronal cells, said cells having migrated to at least one specific location in the mammal'"'"'s brain;

b) administering the mammal the substance; and

c) observing the mammal for an effect of the substance.