Unextracted tooth root canal filler and dental tissue regeneration method for unextracted tooth

Abstract

Disclosed is a root canal filler for non-extracted tooth which causes no internal resorption or external resorption in a tooth with complete root formation, shows no odontoclast, and contributes to the regeneration of a dental tissue in which odontoblasts are smoothly aligned on the dentin wall. After pulpectomy or enlargement/cleaning of an infected root canal, a root canal filler for non-extracted tooth, which comprises tooth pulp stem cells and an extracellular matrix, is inserted into the apical side of the root canal of the non-extracted tooth. The tooth pulp stem cells may be, for example, dental pulp CXCR4-positive cells. It is preferred to attach, to the crown side of the root canal, migration factor(s) including at least one factor selected from among a cell migration factor, a cell proliferation factor, a neurotrophic factor and an angiogenic factor.

1 . An unextracted tooth root canal filler formed to be inserted in an apical part of a root canal of an unextracted tooth after pulpectomy or after enlargement and cleaning of the infected root canal, the root canal filler comprising: dental pulp stem cells and an extracellular matrix. 
     
     
         2 . The unextracted tooth root canal filler of  claim 1 , wherein the dental pulp stem cells comprise at least one type of dental pulp cells selected from the group consisting of dental pulp CXCR4-positive cells, SSEA-4-positive cells, FLK-1-positive cells, CD105-positive cells, dental pulp SP cells, CD31-negative and CD146-negative cells, CD24-positive cells, CD150-positive cells, CD29-positive cells, CD34-positive cells, CD44-positive cells, CD73-positive cells, and CD90-positive cells. 
     
     
         3 . The unextracted tooth root canal filler of  claim 2 , wherein the dental pulp SP cells are selected from the group consisting of CXCR4-positive cells, SSEA-4-positive cells, FLK-1-positive cells, CD31-negative and CD146-negative cells, CD24-positive cells, CD105-positive cells, CD150-positive cells, CD29-positive cells, CD34-positive cells, CD44-positive cells, CD73-positive cells, and CD90-positive cells. 
     
     
         4 . The unextracted tooth root canal filler of  claim 1 , wherein the dental pulp stem cells are transplanted to the apical part of the root canal, and a chemotactic factor comprising at least one factor selected from the group consisting of a cell chemotactic factor, a cell growth factor, a neurotrophic factor, and an angiogenic factor is transplanted to a tooth crown part of the root canal. 
     
     
         5 . The unextracted tooth root canal filler of  claim 4 , wherein the cell chemotactic factor is at least one cell chemotactic factor selected from the group consisting of SDF-1, VEGF, G-CSF, SCF, MMP3, Slit, and GM-CSF. 
     
     
         6 . The unextracted tooth root canal filler of  claim 4 , wherein the cell growth factor is at least one cell growth factor selected from the group consisting of IGF, bFGF, or PDGF. 
     
     
         7 . The unextracted tooth root canal filler of  claim 4 , wherein the neurotrophic factor is at least one neurotropic factor selected from the group consisting of GDNF, BDNF, NGF, Neuropeptide Y, and Neurotrophin 3. 
     
     
         8 . The unextracted tooth root canal filler of  claim 1 , wherein the extracellular matrix is made of biocompatible materials containing at least one biocompatible material selected from the group consisting of collagen, synthetic proteoglycans, gelatin, hydrogel, fibrin, phosphophorin, heparan sulfate, heparin, laminin, fibronectin, alginic acid, hyaluronic acid, chitin, PLA, PLGA, PEG, PGA, PDLLA, PCL, hydroxyapatite, β-TCP, calcium carbonate, titanium, and gold. 
     
     
         9 . The unextracted tooth root canal filler of  claim 1 , wherein a concentration of the dental pulp stem cells in the extracellular matrix is in the range from 1×10 3  cells/μl to 1×10 6  cells/μl both inclusive. 
     
     
         10 . A dental tissue regeneration method without tooth extraction, wherein dental tissues in a root canal are regenerated by transplantation of an unextracted tooth root canal filler including dental pulp stem cells and an extracellular matrix into an apical part of the root canal of the unextracted tooth after pulpectomy or after enlargement and cleaning of the infected root canal. 
     
     
         11 . The dental tissue regeneration method of  claim 10 , wherein the dental pulp stem cells comprise at least one type of dental pulp cell selected from the group consisting of dental pulp CXCR4-positive cells, SSEA-4-positive cells, FLK-1-positive cells, CD105-positive cells, dental pulp SP cells, CD31-negative and CD146-negative cells, CD24-positive cells, CD150-positive cells, CD29-positive cells, CD34-positive cells, CD44-positive cells, CD73-positive cells, and CD90-positive cells. 
     
     
         12 . The dental tissue regeneration method of  claim 11 , wherein the dental pulp SP cells are selected from the group consisting of CXCR4-positive cells, SSEA-4-positive cells, FLK-1-positive cells, CD31-negative and CD146-negative cells, CD24-positive cells, CD105-positive cells, CD150-positive cells, CD29-positive cells, CD34-positive cells, CD44-positive cells, CD73-positive cells, and CD90-positive cells. 
     
     
         13 . The dental tissue regeneration method of  claim 10 , wherein in the unextracted tooth root canal filler, the dental pulp stem cells are transplanted to the apical part of the root canal, and a chemotactic factor comprising at least one factor selected from the group consisting of a cell chemotactic factor, a cell growth factor, a neurotrophic factor, and an angiogenic factor is transplanted to a tooth crown part of the root canal. 
     
     
         14 . The dental tissue regeneration method of  claim 13 , wherein the cell chemotactic factor is at least one cell chemotactic factor selected from the group consisting of SDF-1, VEGF, G-CSF, SCF, MMP3, Slit, and GM-CSF. 
     
     
         15 . The dental tissue regeneration method of  claim 13 , wherein the cell growth factor is at least one cell growth factor selected from the group consisting of IGF, bFGF, and PDGF. 
     
     
         16 . The dental tissue regeneration method of  claim 13 , wherein the neurotrophic factor is at least one neurotrophic factor selected from the group consisting of GDNF, BDNF, NGF, Neuropeptide Y, and Neurotrophin 3. 
     
     
         17 . The dental tissue regeneration method of  claim 10 , wherein the extracellular matrix is made of biocompatible materials containing at least one biocompatible material selected from the group consisting of collagen, synthetic proteoglycans, gelatin, hydrogel, fibrin, phosphophorin, heparan sulfate, heparin, laminin, fibronectin, alginic acid, hyaluronic acid, chitin, PLA, PLGA, PEG, PGA, PDLLA, PCL, hydroxyapatite, β-TCP, calcium carbonate, titanium, and gold. 
     
     
         18 . The dental tissue regeneration method of  claim 10 , wherein the root canal is enlarged before transplantation of the root canal filler into the apical part of the root canal, thereby enlarging the apical part of the root canal to a predetermined size. 
     
     
         19 . The dental tissue regeneration method of  claim 10 , wherein a concentration of the dental pulp stem cells in the extracellular matrix is in the range from 1×10 3  cells/μl to 1×10 6  cells/μl both inclusive.