METHODS OF USING ADIPOSE TISSUE-DERIVED CELLS IN THE TREATMENT OF THE LYMPHATIC SYSTEM AND MALIGNANT DISEASE

• US 20110206646A1
• Filed: 02/18/2011
• Published: 08/25/2011
• Est. Priority Date: 08/19/2008
• Status: Active Grant

• Current Assignee: Lorem Vascular Pte. Ltd.
• Original Assignee: Cytori Therapeutics Incorporated
• Inventors: Alfonso, Zeni, Fraser, John K.
• Granted Patent: US 8,784,801 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• 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 35/35 Fat tissue; Adipocytes; Stromal cells; Connective tissues adipose-derived stem cells A61K35/28; collagen A61K38/39
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 5/0651 Lymph nodes
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells

Abstract

Aspects of the invention provides methods for preparing and using adipose-tissue-derived stem and progenitor cells, adipose-tissue-derived lymphatic endothelial cells, and cells capable of differentiating into lymphatic endothelial cells to treat disorders of the lymphatic system and to modulate expansion, repair, and/or regeneration of the lymphatic system. The invention further provides using adipose-tissue-derived lymphatic endothelial cells and cells capable of differentiating into lymphatic endothelial cells for delivery of therapeutic agents to tumor cells as a means for treating malignant disease, and assays to screen for drugs that modulate lymphatic system expansion, repair or regeneration.

Claims

1. An isolated population of adipose-derived cells comprising lymphatic endothelial cells (LECs) and pre-LECs, wherein greater than 5% of said isolated population of adipose-derived cells express FLT-4.

2. The isolated population of adipose-derived cells of claim 1, wherein greater than 30% of said population of adipose-derived cells express FLT-4.

3. The isolated population of adipose-derived cells of claim 1, wherein about 40% of said population of adipose-derived cells express FLT-4.

4. The isolated population of adipose-derived cells of claim 1, wherein greater than 5% of said population of adipose-derived cells also express CD45.

5. The isolated population of adipose-derived cells of claim 1, wherein greater than 5% of said population of adipose-derived cells also express CD34.

6. The isolated population of adipose-derived cells of claim 1, wherein greater than 10% of said population of adipose-derived cells also express CD45.

7. The isolated population of adipose-derived cells of claim 1, wherein greater than 10% of said population of adipose-derived cells also express CD34.

8. A composition comprising the isolated population of adipose-derived cells of claim 1 mixed with a biological material, an additive, a support, a medical device, a prosthetic, a cell differentiation factor, a growth promoter, an immunosuppressive agent, an anti-apoptosis agent, a biological tissue, a tissue graft, a portion of unprocessed adipose tissue, a collagen, a population of adipose-derived stem cells, a population of adipose-derived endothelial cells, or a population of adipose derived progenitor cells.

9. A method of lymphatic endothelial cell (LEC) and pre-LEC transplantation in a mammal comprising:

identifying a mammal in need of LECs or pre-LECs; and

providing an isolated population of adipose-derived cells comprising lymphatic endothelial cells (LECs) and pre-LECs, wherein greater than 5% of said population of adipose-derived cells express FLT-4, to said identified mammal.

10. The method of claim 9, wherein said isolated population of adipose-derived cells is mixed with a biological material, an additive, a medical device, a prosthetic, a cell differentiation factor, a growth promoter, an immunosuppressive agent, an anti-apoptosis agent, a biological tissue, a tissue graft, a portion of unprocessed adipose tissue, a collagen, a population of adipose-derived stem cells, a population of adipose-derived endothelial cells, or a population of adipose derived progenitor cells.

11. The method of claim 9, further comprising assessing said mammal for induction of lymphatic cell proliferation, lymphatic cell expansion, lymphatic vessel formation, or lymphatic tissue formation.

12. The method of claim 9, wherein said cell transplantation accompanies a breast augmentation procedure.

13. The method of claim 9, wherein said identified mammal has a disease or disorder selected from the group consisting of:

obesity, lymphatic vessel aplasia, edema, lymphatic vessel loss or damage due to surgical intervention, lymphatic vessel loss, damage or deficiency due to organ or tissue transplant, reduced lymphatic vessel function due to lymphatic vessel blockage, lymphatic vessel occlusion, elephantiasis, cardiovascular disease, heart disease, chronic granulomatous disease (CGD), a lymphatic malignancy, Hodgkin'"'"'s Disease, a non-Hodgkin'"'"'s lymphoma, Castleman Disease;

a non-lymphatic malignancy, a breast cancer, an ovarian cancer, a colorectal cancer, a lung cancer, a liver cancer, a stomach cancer, a pancreatic cancer, and a cancer of the central nervous system.

14. A method of inducing expansion of lymph vessels in a mammal comprising:

identifying a mammal in need of an expansion of lymph vessels; and

providing an isolated population of adipose-derived cells comprising lymphatic endothelial cells (LECs) and pre-LECs, wherein greater than 5% of said population of adipose-derived cells express FLT-4, to said identified mammal.

15. The method of claim 14, wherein said isolated population of adipose-derived cells is mixed with a biological material, an additive, a medical device, a prosthetic, a cell differentiation factor, a growth promoter, an immunosuppressive agent, an anti-apoptosis agent, a biological tissue, a tissue graft, a portion of unprocessed adipose tissue, a collagen, a population of adipose-derived stem cells, a population of adipose-derived endothelial cells, or a population of adipose derived progenitor cells.

16. The method of claim 14, further comprising assessing said mammal for one or more of the following:

induction of lymphatic cell proliferation, lymphatic cell expansion, lymphatic vessel formation, and lymphatic tissue formation.

17. The method of claim 14, wherein said providing step accompanies a breast augmentation procedure.

18. The method of claim 14, wherein said identified mammal has a disease or disorder selected from the group consisting of:

obesity, lymphatic vessel aplasia, edema, lymphatic vessel loss or damage due to surgical intervention, lymphatic vessel loss, damage or deficiency due to organ or tissue transplant, reduced lymphatic vessel function due to lymphatic vessel blockage, lymphatic vessel occlusion, elephantiasis, cardiovascular disease, heart disease, chronic granulomatous disease (CGD), a lymphatic malignancy, Hodgkin'"'"'s Disease, a non-Hodgkin'"'"'s lymphoma, Castleman Disease;

a non-lymphatic malignancy, a breast cancer, an ovarian cancer, a colorectal cancer, a lung cancer, a liver cancer, a stomach cancer, a pancreatic cancer, and a cancer of the central nervous system.