Isolated stromal cells and methods of using the same

Abstract

Methods of treating patients who are suffering from a disease, disorder or condition characterized by a bone cartilage or lung defect are disclosed. The methods comprising the step of intravenous administration of stromal cells isolated from normal syngeneic individuals or intravenous administration of stromal cells isolated from the patient subsequent to correction of the genetic defect in the isolated cells. Implant devices comprising a container that has at least one membrane surface and stromal cells isolated from bone marrow that comprise a gene construct are disclosed. The gene construct in the stromal cells comprises a nucleotide sequence that encodes a beneficial protein operably linked to regulatory elements which function in stromal cells. Methods of treating individuals with diseases, disorders or conditions which can be treated with a beneficial protein, including diseases, disorders or conditions characterized by gene defects are disclosed. The methods comprise introducing into such individuals, stromal cells that are administered in a manner that physically isolates them from the recipient's immune system and that comprise a gene construct that comprises a nucleotide sequence that encodes a beneficial protein operably linked to regulatory elements which function in stromal cells.

1 .- 54 . (canceled) 
   
   
       55 . A method of treating a patient who is suffering from a disease, disorder or condition characterized by a cartilage or lung defect, comprising
 a) obtaining stromal cells from a donor who is not suffering from a disease, disorder or condition characterized by a cartilage or lung defect and who is syngeneic with the patient;   b) isolating stromal cells from the sample; and   c) administering the isolated stromal cells by intravenous infusion to the patient.   
   
   
       56 . The method of  claim 55 , wherein the patient undergoes bone marrow ablation prior to administration of the isolated stromal cells. 
   
   
       57 . The method of  claim 56 , wherein the stromal cells are administered together with hematopoietic precursor cells from a bone marrow sample from a donor who is not suffering from a disease, disorder or condition characterized by a cartilage or lung defect and who is syngeneic with the patient. 
   
   
       58 .- 59 . (canceled) 
   
   
       60 . The method of  claim 55 , wherein the disease, disorder or condition is characterized by a defect in the patient's cartilage or lungs. 
   
   
       61 .- 64 . (canceled) 
   
   
       65 . A method of treating patient who suffering from a disease, disorder or condition characterized by a mutated, non- functioning or under-expressed gene which results in a defect in the cartilage or lungs of the patient, comprising the steps of
 a) obtaining a bone marrow sample from the patient;   b) isolating stromal cells from the sample;   c) transfecting the stromal cells with a normal copy of the mutated, non-functioning or under-expressed gene, wherein the copy of the gene is operably linked to functional regulatory elements; and   d) administering the transfected stromal cells to the patient by intravenous infusion.   
   
   
       66 . The method of  claim 65 , wherein the patent undergoes bone marrow ablation prior to administration of the transfected stromal cells. 
   
   
       67 .- 69 . (canceled) 
   
   
       70 . The method of  claim 65 , wherein the disease, disorder or condition is characterized by a defect in the patient's cartilage or lungs. 
   
   
       71 .- 74 . (canceled) 
   
   
       75 . An implant device comprising:
 a container having at least one membrane surface   stromal cells that comprise a gene construct, the gene construct comprising a nucleotide sequence that encodes a beneficial protein operably linked to regulatory elements which function in the stromal cell.   
   
   
       76 .- 80 . (canceled) 
   
   
       81 . A method of treating an individual with a disease, disorder or condition which can be treated with a beneficial protein, comprising
 administering to the individual immunologically isolated stromal cells that comprise a gene construct, the gene construct comprising a nucleotide sequence that encodes a beneficial protein operably linked to regulatory elements which function in the stromal cell.   
   
   
       82 .- 83 . (canceled) 
   
   
       84 . The method of  claim 81 , wherein the immunologically isolated stromal cells are within an implant device that comprises the stromal cells and a container having at least one membrane surface. 
   
   
       85 .- 89 . (canceled) 
   
   
       90 . Immunologically isolated stromal cells that comprise a gene construct, the gene construct comprising a nucleotide sequence that encodes a beneficial protein operably linked to regulatory elements which functions in the stromal cell. 
   
   
       91 . (canceled) 
   
   
       92 . The immunologically isolated stromal cells of  claim 90 , wherein the stromal cells are microencapsulated. 
   
   
       93 . A method of treating patient who is suffering from a disease, disorder or condition characterized by a cartilage or lung defect, comprising
 a) obtaining a bone marrow sample from a donor who is not suffering from a disease, disorder or condition characterized by a cartilage or lung defect and who is syngeneic with the patient, and   b) administering a therapeutically effective amount of the bone marrow by intravenous infusion to the patient.   
   
   
       94 . The method of  claim 93 , wherein the patent undergoes bone marrow ablation prior to administration of the bone marrow. 
   
   
       95 . The method of  claim 93 , wherein the disease, disorder or condition is characterized by a defect in the patient's cartilage. 
   
   
       96 . (canceled) 
   
   
       97 . A method of treating patient who is suffering from a disease, disorder or condition characterized by a mutated, non-functioning or under-expressed gene which results in a defect in the cartilage or lungs of the patient, comprising
 a) obtaining a bone marrow sample from the patient;   b) isolating stromal cells from the sample;   c) culturing the stromal cells under conditions which result in replication of the stromal cells into an expanded culture of stromal cells; and   d) administering stromal cells of the expanded culture of stromal cells to the patient by intravenous infusion.   
   
   
       98 . The method of  claim 97 , wherein the patent undergoes bone marrow ablation prior to administration of stromal cells. 
   
   
       99 . The method of  claim 98 , wherein the stromal cells are administered together with hematopoietic precursor cells from the sample. 
   
   
       100 . (canceled) 
   
   
       101 . The method of  claim 97 , wherein the disease, disorder or condition is characterized by a defect in the patient's cartilage or lungs. 
   
   
       102 .- 105 . (canceled) 
   
   
       106 . A method of repairing or regenerating heart tissue in a patient suffering from a disease, disorder, or condition of the heart, comprising administering to the patient autologous or allogeneic bone marrow stromal cells, wherein the cells differentiate into heart cells in the heart of the patient, thereby repairing or regenerating heart tissue. 
   
   
       107 . A method of treating a disease, disorder or condition in a patient suffering from a disease, disorder or condition of the heart, the method comprising
 a) obtaining a bone marrow sample from a donor who is not suffering from a disease, disorder or condition of the heart and who is syngeneic with the patient;   b) isolating stromal cells from the sample; and   c) administering the isolated stromal cells by intravenous infusion to the patient.   
   
   
       108 . A method for repairing or regenerating a blood vessel in a patient, the method comprising administering culture expanded autologous or allogeneic bone marrow stromal cells to the patient, wherein the cells differentiate into cells of a blood vessel in the patient, thereby repairing or regenerating the blood vessel in the patient. 
   
   
       109 . A method of treating a disease, disorder or condition in a patient wherein the disease, disorder or condition is characterized by a defect in a blood vessel, the method comprising
 a) obtaining a bone marrow sample from a donor who is not suffering from a disease, disorder or condition characterized by a defect in a blood vessel and who is syngeneic with the patient;   b) isolating stromal cells from the sample; and   c) administering the isolated stromal cells by intravenous infusion to the patient.