Postnatal stem cells and uses thereof

Abstract

The invention generally relates to postnatal dental stem cells and methods for their use. More specifically, the invention relates in one aspect to postnatal dental pulp stem cells, use of the cells to generate dentin, and differentiation of the cells. In another aspect, the invention relates to human postnatal deciduous dental pulp multipotent stem cells, use of the cells to generate dentin, and differentiation of the cells.

We claim: 
     
         1 . A method of generating dentin in a subject, comprising
 implanting into the subject an isolated population of human postnatal deciduous dental pulp multipotent stem cells, wherein
 the human postnatal deciduous dental pulp multipotent stem cells are from a postnatal deciduous tooth; 
 human postnatal deciduous dental pulp multipotent stem cells in the population differentiate into an odontoblast; 
 human postnatal deciduous dental pulp multipotent stem cells in the population can proliferate to over 140 population doublings; and 
 the isolated population of human postnatal deciduous dental pulp mulitpotent stem cells were expanded ex vivo, wherein the human postnatal 
   deciduous dental pulp multipotent stem cells in the population express CD146, thereby allowing human postnatal deciduous dental pulp cells in the population to generate dentin in the subject.   
     
     
         2 . The method of  claim 1 , wherein human postnatal deciduous dental pulp multipotent stem cells within the population express STRO-1. 
     
     
         3 . The method of  claim 1 , wherein the human postnatal deciduous dental pulp multipotent stem cells with the population are transfected with an exogenous nucleic acid segment that encodes a heterologous product, and wherein the cells express the product. 
     
     
         4 . The method of  claim 1 , wherein the postnatal deciduous tooth is an incisor. 
     
     
         5 . The method of  claim 1 , wherein the isolated population of human postnatal dental pulp cells were obtained by the process of:
 separating pulp from a remnant crown of a human postnatal deciduous tooth;   digesting the pulp in collagenase and dispase to form digested pulp;   producing a single cell suspension from the digested pulp;   isolating single cells that adhere to a tissue culture surface from the single cell suspension; and   culturing the single cells in vitro.   
     
     
         6 . The method of  claim 1 , wherein human postnatal deciduous dental pulp multipotent stem cells within the population do not express STRO-1. 
     
     
         7 . The method of  claim 1 , wherein the isolated population of human postnatal deciduous dental pulp multipotent stem cells is implanted into a tooth of the subject. 
     
     
         8 . The method of  claim 1 , wherein the tooth of the subject has been traumatized. 
     
     
         9 . The method of  claim 8 , wherein the subject has undergone a root canal, and wherein the isolated population of human postnatal deciduous dental pulp multipotent stem cells is implanted into a void in a tooth created by the root canal. 
     
     
         10 . The method of  claim 1 , wherein the isolated population of human postnatal deciduous dental pulp multipotent stem cells is implanted with a carrier. 
     
     
         11 . The method of  claim 10 , wherein the carrier is hydroxyapatite/tricalcium phosphate. 
     
     
         12 . A method of generating dentin, comprising:
 a. contacting pre-existing dentin with an isolated population of human postnatal deciduous dental pulp multipotent stem cells, wherein
 the human postnatal deciduous dental pulp multipotent stem cells are from a postnatal deciduous tooth; 
 human postnatal deciduous dental pulp multipotent stem cells in the population differentiate into an odontoblast; 
 human postnatal deciduous dental pulp multipotent stem cells in the population can proliferate to over 140 population doublings; and 
   the isolated population of human postnatal deciduous dental pulp mulitpotent stem cells were expanded ex vivo, wherein the human postnatal deciduous dental pulp multipotent stem cells in the population express CD146; and   b. incubating the pre-existing dentin with the isolated population of   human postnatal deciduous multipotent stem cells,   
       thereby producing treated dentin. 
     
     
         13 . The method of  claim 2 , wherein the pre-existing dentin is contacted with the dental stem cell in vivo or in vitro. 
     
     
         14 . The method of  claim 2 , wherein the pre-existing dentin is contained within a tooth. 
     
     
         15 . The method of  claim 2 , further comprising washing the treated dentin with a fluid. 
     
     
         16 . The method of  claim 15 , wherein the fluid is water, a biological solvent, or a biological buffer. 
     
     
         17 . The method of  claim 12 , further comprising washing the pre-existing dentin with an acid solution or a base solution. 
     
     
         18 . The method of  claim 17 , wherein the acid solution is acetic acid, phosphoric acid, formic acid, sulfuric acid, hydrochloric acid, hydrofluoric acid, hydroiodic acid, nitric acid, or hydrobromic acid. 
     
     
         19 . The method of  claim 17 , wherein the base solution comprises a base selected from the group consisting of sodium hydroxide, potassium hydroxide, or ammonium hydroxide. 
     
     
         20 . The method of  claim 14 , wherein there has been trauma to the tooth. 
     
     
         21 . The method of  claim 20 , wherein the trauma is a root canal. 
     
     
         22 . The method of  claim 12 , wherein human postnatal deciduous dental pulp multipotent stem cells within the population express STRO-1.