Use of term amniotic fluid cells for the treatment of acute and chronic respiratory diseases

Abstract

Methods for purifying, culturing and selecting mesenchymal stem cell (MSC) subpopulations with neonatal quality and adult tissue specificity that are for use in production of advanced therapeutic medicinal products.

What is claimed is: 
     
         1 . A method of treating acute respiratory distress syndrome in a patient in need thereof, comprising:
 administering term amniotic fluid (TAF) lung mesenchymal stem cells (MSCs) to the patient, wherein the Lung TAF MSCs have been obtained by:
 performing adherence selection on TAF cells to obtain TAF adherence cells; 
 passaging the TAF adherence cells to obtain TAF mesenchymal stem cells (TAF MSCs); and 
 selecting TAF MSCs to obtain lung TAF MSCs. 
   
     
     
         2 . The method of  claim 1 , wherein selecting TAF MSCs to obtain Lung TAF MSCs comprises selecting TAF MSCs that express Endosialin. 
     
     
         3 . The method of  claim 2 , wherein selecting TAF MSCs to obtain Lung TAF MSCs comprises selecting TAF MSCs that express DDR1. 
     
     
         4 . The method of  claim 2 , wherein selecting TAF MSCs to obtain Lung TAF MSCs comprises selecting TAF MSCs that express LRRC38. 
     
     
         5 . The method of  claim 1 , wherein selecting TAF MSCs to obtain lung TAF MSCs comprises selecting TAF MSCs that express a Group A surface marker selected from the group consisting of PCDH19, DDR1, MME, IFITM10, BGN, NOTCH3, SULF1, TNFSF18, BDKRB1, FLT1, PDGFRA, TNFSF4, UNC5B, FAP, CASP1, CD248, DDR2, PCDH18, LRRC38, and CRLF1. 
     
     
         6 . The method of  claim 5 , wherein the selecting further comprises a first sorting step to direct TAF MSCs that express Endosialin into a first output group, wherein the selecting TAF MSCs that express the Group A surface marker is a second sorting step to direct TAF MSCs from the first output group into a second output group. 
     
     
         7 . The method of  claim 1 , wherein selecting lung TAF MSCs comprises excluding TAF MSCs that express a Group B surface marker selected from the group consisting of CD24, ITGB4, TNFSF10, GFRA1, CD74, FGFR4, HAVCR1, and OSCAR. 
     
     
         8 . The method of  claim 1 , wherein the lung TAF MSCs are administered at a concentration of about 1-2 million cells per kg. 
     
     
         9 . The method of  claim 1 , wherein administering the lung TAF MSCs comprises administering the lung TAF MSCs via an intravenous drip. 
     
     
         10 . The method of  claim 9 , wherein the intravenous drip comprises about 40 drops per minute. 
     
     
         11 . A method for obtaining lung mesenchymal stem cells from amniotic fluid, comprising:
 providing term amniotic fluid (TAF);   removing particulate material from the TAF to obtain purified TAF cells;   performing adherence selection on the purified TAF cells to obtain TAF adherence cells;   passaging the TAF adherence cells to obtain TAF mesenchymal stem cells (TAF MSCs); and   selecting TAF MSCs that express Endosialin to obtain Lung TAF MSCs.   
     
     
         12 . The method of  claim 11 , wherein the step of selecting TAF MSCs that express Endosialin to obtain lung TAF MSCs further comprises selecting lung TAF MSCs that express a Group A surface marker selected from the group consisting of PCDH19, DDR1, MME, IFITM10, BGN, NOTCH3, SULF1, TNFSF18, BDKRB1, FLT1, PDGFRA, TNFSF4, UNC5B, FAP, CASP1, CD248, DDR2, PCDH18, LRRC38, and CRLF1. 
     
     
         13 . The method of  claim 11 , wherein the step of selecting TAF MSCs that express Endosialin to obtain lung TAF MSCs further comprises excluding TAF MSCs that express a Group B surface marker selected from the group consisting of CD24, ITGB4, TNFSF10, GFRA1, CD74, FGFR4, HAVCR1, and OSCAR. 
     
     
         14 . The method of  claim 12 , wherein the selecting step comprises selecting TAF MSCs that express at least two surface markers from the Group A surface markers. 
     
     
         15 . The method of  claim 14 , wherein the selecting step comprises selecting TAF MSCs that express at least three surface markers from the Group A surface markers. 
     
     
         16 . The method of  claim 15 , wherein the selecting step comprises selecting TAF MSCs that express at least four surface markers from the Group A surface markers. 
     
     
         17 . Isolated cells obtainable by the method according to  claim 1 , said cells expressing Endosialin. 
     
     
         18 . A population of term amniotic fluid (TAF) lung mesenchymal stem cells (MSCs) for use in a method of treating acute respiratory distress syndrome in a patient in need thereof, wherein the Lung TAF MSCs have been obtained by:
 performing adherence selection on TAF cells to obtain TAF adherence cells;   passaging the TAF adherence cells to obtain TAF mesenchymal stem cells (TAF MSCs); and   selecting TAF MSCs to obtain Lung TAF MSCs.   
     
     
         19 . A composition comprising the isolated population of term amniotic fluid (TAF) mesenchymal stem cells according to  claim 18  and a pharmaceutically acceptable carrier for said TAF mesenchymal stem cells.