Methods of using adipose tissue-derived cells in the treatment of the lymphatic system and malignant disease

• US 9,486,484 B2
• Filed: 07/21/2014
• Issued: 11/08/2016
• Est. Priority Date: 08/19/2008
• Status: Expired due to Fees

• Current Assignee: Lorem Vascular Pte. Ltd.
• Original Assignee: Cytori Therapeutics Incorporated
• Inventors: Alfonso, Zeni, Fraser, John K.
• Primary Examiner(s): Lankford, Blaine
• Application Number:
  US14/336,755
• Publication Number:
  US 20140369970A1
• Time in Patent Office: 841 Days
• Field of Search: None
• US Class Current: 1/1
• 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. A method of treating edema in a subject in need thereof, comprising:

identifying a subject having edema; and

administering to said subject 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.

2. The method of claim 1, wherein the edema is lymphedema.

3. The method of claim 1, wherein said subject has a wound.

4. The method of claim 3, wherein said wound is a burn.

5. The method of claim 3, wherein said wound is a skin wound following grafting.

6. The method of claim 3, wherein said wound is a radiation wound.

7. The method of claim 1, wherein said isolated population of adipose-derived cells comprising lymphatic endothelial cells (LECs) and pre-LECs is administered by injection into a lymph node.

8. The method of claim 1, wherein said isolated population of adipose-derived cells comprising lymphatic endothelial cells (LECs) and pre-LECs is administered by injection into lymphatic vessels.

9. The method of claim 1, wherein said isolated population of adipose-derived cells comprising lymphatic endothelial cells (LECs) and pre-LECs is administered by injection into tissue space.

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

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

12. The method of claim 1, wherein greater than 5% of said population of adipose-derived cells also express CD14.

13. The method of claim 1, wherein said isolated population of adipose-derived cells is mixed with an additive prior to administering the adipose-derived cells to the subject.

14. The method of claim 13, wherein said additive is selected from the group consisting of an anti-apoptosis agent, a growth factor, a tissue graft, a portion of unprocessed adipose tissue, a population of adipose-derived stem cells, a population of adipose-derived endothelial cells, population of adipose-derived progenitor cells, a cell differentiation factor.

15. The method of claim 1, wherein said identification comprises examination of a tissue biopsy, fluorescence micorlymphangiography, computed tomography, X-ray lymphography, dual0site fluorescence angiography, isotope lymphography, laser-Doppler analysis, magnetic resonance imaging, ultrasonography, or any combination thereof.

16. The method of claim 1, wherein said isolated population of adipose-derived cells is not cultured prior to providing the isolated population of adipose-derived cells to the subject.

17. The method of claim 1, wherein said isolated population of adipose-derived cells is cultured in vitro prior to providing the isolated population of adipose-derived cells to the subject.

18. The method of claim 1, wherein said isolated population of adipose-derived cells is obtained by processing adipose tissue in a cell processing device configured to maintain a closed pathway.

19. The method of claim 1, further comprising analyzing said edema following the administration of said isolated population of adipose-derived cells.

20. The method of claim 1, wherein the isolated population of adipose-derived cells comprising LECs and pre-LECs is cryopreserved.