Treatment of pain using amnion derived adherent cells

Patent metadata

Field	Value
Publication number	US-2016166618-A1
Application number	US-201314436746-A
Country	US
Kind code	A1
Filing date	Oct 18, 2013
Priority date	Oct 19, 2012
Publication date	Jun 16, 2016
Grant date	—

Abstract

Provided herein are methods of treatment of an individual having pain, e.g., neuropathic pain, comprising administering to the individual a therapeutically effective amount of tissue culture plastic adherent amnion-derived cells (AMDACs). Because mammalian placentas are plentiful and are normally discarded as medical waste, they represent a unique source of medically-useful stem cells.

First claim

What is claimed is:

1 . A method of treating pain in an individual, comprising administering to the individual a therapeutically effective amount of OCT-4−, tissue culture surface-adherent amnion-derived adherent cells (AMDACs), or culture medium conditioned by AMDACs, wherein the therapeutically effective amount is an amount sufficient to cause a detectable improvement in said pain.

2 . The method of claim 1 , wherein said method additionally comprises determining one or more first levels of pain in said individual prior to administration of said AMDACs, and determining one or more second levels of pain in said individual after administration of said AMDACs, wherein said therapeutically effective amount of AMDACs reduces said one or more second levels of said pain as compared to said one or more first levels of pain.

3 . The method of claim 2 , wherein said one or more first levels of pain and said one or more second levels of pain are determined by a pain assessment scale.

4 . The method of claim 3 , wherein said pain assessment scale is the Numeric Pain Intensity Scale; the Pain Quality Assessment Scale; the Simple Descriptive Pain Intensity Scale; the Visual Analog Scale; the Wong-Baker FACES Pain Rating Scale; the FLACC scale; the CRIES scale; the COMFORT scale; or evoked pain measure induced by subjecting the patient to cold, heat or mechanical stimuli.

5 . The method of claim 1 , wherein said method additionally comprises determining a first level of one or more physiological indicia of pain in said individual prior to administration of said AMDACs, and determining a second level of one or more physiological indicia of pain in said individual after administration of said AMDACs, wherein said therapeutically effective amount of AMDACs reduces said second level as compared to said first level.

6 . The method of claim 5 , wherein said physiological indicium of pain is heart rate in the individual.

7 . The method of claim 6 , wherein said heart rate in said individual is lower after said administration compared to said heart rate in said individual before said administration.

8 . The method of claim 5 , wherein said physiological indicium of pain is the systolic of said individual.

9 . The method of claim 8 , wherein said systolic of said individual is lower after said administration compared to said systolic in said individual before said administration.

10 . The method of claim 5 , wherein said physiological indicium of pain is the diastolic of said individual.

11 . The method of claim 10 , wherein said diastolic of said individual is lower after said administration compared to said diastolic in said individual before said administration.

12 . The method of claim 1 , wherein said AMDACs are HLA-G − , as determinable by RT-PCR.

13 . The method of claim 1 , wherein said AMDACs are additionally CD49f + , as determinable by flow cytometry.

14 . The method of claim 13 , wherein said AMDACs are OCT-4 − , HLA-G − and CD49f′.

15 . The method of claim 1 , wherein said AMDACs are CD90 + , CD105 + , or CD117 − as determinable by flow cytometry.

16 . The method of claim 15 , wherein said AMDACs are CD90 + , CD105 + , and CD117 − as determinable by flow cytometry.

17 . The method of claim 16 , wherein said AMDACs are OCT-4 − and HLA-G − , as determinable by RT-PCR, and CD49f + , CD90 + , CD105 + , and CD117 − as determinable by flow cytometry.

18 . The method of claim 1 , wherein said AMDACs are VEGFR1/Flt-1 + (vascular endothelial growth factor receptor 1) and VEGFR2/KDR + (vascular endothelial growth factor receptor 2), as determinable by immunolocalization.

19 . The method of claim 1 , wherein said AMDACs are one or more of CD9 + , CD10 + , CD44 + , CD54 + , CD98 + , Tie-2 + (angiopoietin receptor), TEM-7 + (tumor endothelial marker 7), CD31 − , CD34 − , CD45 − , CD133 − , CD143 − (angiotensin-I-converting enzyme, ACE), CD146 − (melanoma cell adhesion molecule), or CXCR4 − (chemokine (C—X—C motif) receptor 4) as determinable by immunolocalization.

20 . The method of claim 1 , wherein said AMDACs are CD9 + , CD10 + , CD44 + , CD54 + , CD98 + , Tie-2 + (angiopoietin receptor), TEM-7 + (tumor endothelial marker 7), CD31 − , CD34 − , CD45 − , CD133 − , CD143 − , CD146 − , and CXCR4 − as determinable by immunolocalization.

21 . The method of claim 1 , wherein said AMDACs are VE-cadherin − as determinable by immunolocalization.

22 . The method of claim 1 , wherein said AMDACs are additionally positive for CD105 + and CD200 + as determinable by immunolocalization.

23 . The method of claim 1 , wherein said AMDACs do not express CD34 as determinable by immunolocalization after exposure to 50 ng/mL VEGF for 7 days.

24 . The method of claim 1 , wherein said AMDACs are comprised within an isolated population of cells, and wherein at least 50% of the cells in said population are said AMDACs.

25 . The method of claim 24 , wherein at least 80% of the cells in said population are said AMDACs.

26 . The method of claim 24 , wherein at least 90% of the cells in said population are said AMDACs.

27 . The method of claim 24 , wherein said population further comprises an isolated second type of cells, and wherein said population is not an amnion, portion of an amnion, or homogenate of an amnion.

28 . The method of claim 27 , wherein said second type of cells are embryonic stem cells, blood cells, stem cells isolated from peripheral blood, stem cells isolated from placental blood, stem cells isolated from placental perfusate, stem cells isolated from placental tissue, stem cells isolated from umbilical cord blood, umbilical cord stem cells, bone marrow-derived mesenchymal stem cells, bone marrow-derived mesenchymal stromal cells, hematopoietic stem cells, somatic stem cells, chondrocytes, fibroblasts, muscle cells, endothelial cells, angioblasts, endothelial progenitor cells, pericytes, cardiomyocytes, myocytes, cardiomyoblasts, myoblasts, or cells manipulated to resemble embryonic stem cells.

29 . The method of claim 27 , wherein said second type of cells comprises at least 10% of cells in said population.

30 . The method of claim 27 , wherein said second type of cells comprises at least 25% of cells in said population.

31 . The method of claim 27 , wherein said second type of cells is hematopoietic stem or progenitor cells.

32 . The method of claim 31 , wherein said hematopoietic stem or progenitor cells are CD34 + cells.

33 . The method of claim 1 , wherein said AMDACs are adherent to tissue culture plastic; are OCT-4 − , as determinable by RT-PCR, and are CD49f + , HLA-G − , CD90 + , CD105 + , and CD117 − , as determinable by immunolocalization; and wherein said AMDACs:
(a) express one or more of CD9, CD10, CD44, CD54, CD98, CD200, Tie-2, TEM-7, VEGFR1/Flt-1, or VEGFR2/KDR (CD309), as determinable by immunolocalization; (b) lack expression of CD31, CD34, CD38, CD45, CD133, CD143, CD144, CD146, CD271, CXCR4, HLA-G, or VE-cadherin, as determinable by immunolocalization, or lack expression of SOX2, as determinable by RT-PCR; (c) express mRNA for ACTA2, ADAMTS1, AMOT, ANG, ANGPT1, ANGPT2, ANGPTL1, ANGPTL2, ANGPTL4, BAI1, CD44, CD200, CEACAM1, CHGA, COL15A1, COL18A1, COL4A1, COL4A2, COL4A3, CSF3, CTGF, CXCL12, CXCL2,

Assignees

• Anthrogenesis Corp
• Anthrogenesis Corproation

Inventors

• Herzberg Uri
• Hariri Robert J
• Gurney Jodi P

Classifications

• A61K35/50 Primary

  Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells · CPC title

• C12N5/0605

  Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly · CPC title

• A61K35/28

  Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells · CPC title

• A61K35/51

  Umbilical cord; Umbilical cord blood; Umbilical stem cells · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title