Methods for treating radiation or chemical injury

• US 10,722,541 B2
• Filed: 07/06/2017
• Issued: 07/28/2020
• Est. Priority Date: 03/22/2011
• Status: Active Grant

• Current Assignee: Pluri Biotech Limited
• Original Assignee: Pluristem Ltd. (Pluri Inc.)
• Inventors: Aberman, Zami, Gorodetsky, Raphael
• Primary Examiner(s): Bertoglio, Valarie E
• Application Number:
  US15/643,144
• Publication Number:
  US 20170368106A1
• Time in Patent Office: 1,118 Days
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C12N 2513/00 : 3D culture
• CPC Class Codes: C12N 2531/00 : Microcarriers
• CPC Class Codes: C12N 5/0605 : Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0663 : Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0667 : Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
• CPC Class Codes: C12N 5/0668 : Mesenchymal stem cells from other natural sources

Abstract

Methods for treating radiation or chemical injury are described that comprise administering to a subject a therapeutically effective amount of adherent stromal cells. Methods of preparing adherent stromal cells and pharmaceutical compositions comprising the cells are also described.

Claims

1. A method for treating a subject with acute radiation sickness, comprising intramuscularly administering to the subject a pharmaceutical composition comprising three-dimensionally cultured placental-derived adherent stromal cells,

wherein the pharmaceutical composition is administered at a dose sufficient to induce an increase in red blood cell counts or an increase in platelet counts, or both;

and

wherein the dose is sufficient to induce an increase in white blood cell counts,

thereby treating the subject.

2. The method of claim 1, wherein exogenous hematopoietic stem cells are not administered to the subject for at least four days following exposure of the subject to radiation.

3. The method of claim 1, wherein the three-dimensionally cultured placental-derived adherent stromal cells are viable following expansion on three-dimensional carriers under conditions supporting cell expansion.

4. The method of claim 3, wherein the three-dimensionally cultured placental-derived adherent stromal cells are viable following detachment from said three-dimensional carriers.

5. The method of claim 4, wherein the three-dimensionally cultured placental-derived adherent stromal cells are viable following cryopreservation.

6. The method of claim 1, wherein the three-dimensionally cultured placental-derived adherent stromal cells exhibit enhanced immunosuppressive activity, relative to placental-derived adherent stromal cells cultured only under two-dimensional culturing conditions.

7. The method of claim 1, wherein the three-dimensionally cultured placental-derived adherent stromal cells exhibit enhanced secretion of Flt-3 ligand, relative to placental-derived adherent stromal cells cultured only under two-dimensional culturing conditions.

8. The method of claim 1, wherein the three-dimensionally cultured placental-derived adherent stromal cells exhibit enhanced secretion of IL-6, relative to placental-derived adherent stromal cells cultured only under two-dimensional culturing conditions.

9. The method of claim 1, wherein the three-dimensionally cultured placental-derived adherent stromal cells exhibit enhanced secretion of stem cell factor (SCF), relative to placental-derived adherent stromal cells cultured only under two-dimensional culturing conditions.

10. The method of claim 1, wherein the three-dimensionally cultured placental-derived adherent stromal cells are viable following culturing on three-dimensional carriers under conditions that support cell expansion without differentiation.

11. The method of claim 1, wherein at least 70% of said three-dimensionally cultured placental-derived adherent stromal cells express CD200.

12. The method of claim 1, wherein said three-dimensionally cultured placental-derived adherent stromal cells are a mixture of maternal-derived placental adherent cells and fetal-derived placental adherent cells.

24. The method of claim 1, further comprising administering at least one additional therapeutically effective amount of three-dimensionally cultured placental-derived adherent stromal cells together with exogenous hematopoietic stem cells to the subject after a matching period following exposure to radiation.

25. The method of claim 1, wherein the three-dimensionally cultured placental-derived adherent stromal cells are first cultured under two-dimensional culturing conditions and then cultured under three-dimensional culturing conditions.

26. The method of claim 1, wherein exogenous hematopoietic stem cells are administered to the subject after a matching period following exposure to radiation.

27. The method of claim 1, wherein exogenous hematopoietic stem cells are not administered to the subject.

28. The method of claim 1, wherein the pharmaceutical composition is administered at least 2 days following exposure of the subject to radiation.

13. A method for treating a subject with a compromised endogenous hematopoietic system, comprising intramuscularly administering to the subject a pharmaceutical composition comprising three-dimensionally cultured placental-derived adherent stromal cells to induce repopulation of endogenous hematopoietic cells,

wherein the pharmaceutical composition is administered at a dose sufficient to induce an increase in red blood cell counts or an increase in platelet counts, or both;

and

wherein the dose is sufficient to induce an increase in white blood cell counts,

thereby treating the subject.

14. The method of claim 13, wherein the subject has been exposed to radiation or chemotherapy, and wherein exogenous hematopoietic stem cells are not administered to the subject for at least four days following the exposure of the subject to radiation or chemotherapy.

15. The method of claim 13, wherein the subject has been exposed to radiation.

16. The method of claim 13, wherein the subject has been exposed to chemotherapy.

17. The method of claim 13, wherein the three-dimensionally cultured placental-derived adherent stromal cells are viable following expansion on three-dimensional carriers under conditions supporting cell expansion.

18. The method of claim 17, wherein the three-dimensionally cultured placental-derived adherent stromal cells are viable following detachment from said three-dimensional carriers.

19. The method of claim 18, wherein the three-dimensionally cultured placental-derived adherent stromal cells are viable following cryopreservation.

20. The method of claim 13, wherein the three-dimensionally cultured placental-derived adherent stromal cells exhibit one or more of the following properties relative to placental-derived adherent stromal cells cultured only under two-dimensional culturing conditions:

enhanced immunosuppressive activity, enhanced secretion of Flt-3 ligand, enhanced secretion of IL-6, and enhanced secretion of stem cell factor (SCF).

21. The method of claim 13, wherein the three-dimensionally cultured placental-derived adherent stromal cells are viable following culturing on three-dimensional carriers under conditions that support cell expansion without differentiation.

22. The method of claim 13, wherein at least 70% of said three-dimensionally cultured placental-derived adherent stromal cells express CD200.

23. The method of claim 13, wherein said three-dimensionally cultured placental-derived adherent stromal cells are a mixture of maternal-derived placental adherent cells and fetal-derived placental adherent cells.