ISOLATED STROMAL CELLS AND METHODS OF USING THE SAME

• US 20090035347A1
• Filed: 03/06/2008
• Published: 02/05/2009
• Est. Priority Date: 03/28/1995
• Status: Abandoned Application

• Current Assignee: Thomas Jefferson University (Main Line Health System)
• Original Assignee: Thomas Jefferson University (Main Line Health System)
• Inventors: Prockop, Darwin J., Pereira, Ruth F., Laptev, Alexey, O'Hara, Michael D., Kulkosky, Joseph, Phinney, Donald, Leeper, Dennis B., Caro, Jose
• Application Number:
  US12/043,903
• Publication Number:
  US 20090035347A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/0025 wherein the non-active part clearly interacts with the delivered nucleic acid
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C07K 14/61 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C07K 14/745 Blood coagulation or fibrinolysis factors
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C12N 2502/1394 Bone marrow stromal cells; whole marrow
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

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.

Claims

1-54. -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.

60. The method of claim 55, wherein the disease, disorder or condition is characterized by a defect in the patient'"'"'s cartilage or lungs.

58-59. -59. (canceled)

61-64. -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.

70. The method of claim 65, wherein the disease, disorder or condition is characterized by a defect in the patient'"'"'s cartilage or lungs.

67-69. -69. (canceled)

71-74. -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. -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.

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.

82-83. -83. (canceled)

85-89. -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.

92. The immunologically isolated stromal cells of claim 90, wherein the stromal cells are microencapsulated.

91. (canceled)

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.

101. The method of claim 97, wherein the disease, disorder or condition is characterized by a defect in the patient'"'"'s cartilage or lungs.

100. (canceled)

102-105. -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.