Methods of treating spinal cord injury and minimizing scarring

• US 9,084,787 B2
• Filed: 03/11/2013
• Issued: 07/21/2015
• Est. Priority Date: 06/14/2006
• Status: Active Grant

• Current Assignee: Stemnion, Inc.
• Original Assignee: Stemnion, Inc.
• Inventors: Sing, George L, Marshall, Vivienne S, Clarke, Diana L
• Primary Examiner(s): Kim, Taeyoon
• Application Number:
  US13/793,593
• Publication Number:
  US 20130189235A1
• Time in Patent Office: 862 Days
• Field of Search: 424/93.7
• US Class Current: 1/1
• 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 35/48 Reproductive organs
• CPC Class Codes: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly

Abstract

The invention is directed to methods of promoting the healing of spinal cord injury. The invention is further directed to methods of minimizing the extent of scarring following spinal cord injury. Such methods utilize novel compositions, including but not limited to extraembryonic cytokine secreting cells (herein referred to as ECS cells), including, but not limited to, amnion-derived multipotent progenitor cells (herein referred to as AMP cells) and conditioned media derived therefrom (herein referred to as amnion-derived cellular cytokine solution or ACCS), each alone or in combination with each other and/or other agents.

Claims

1. A method for stimulating growth or regeneration of spinal cord cells following spinal cord injury in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a composition comprising Amnion-derived Multipotent Progenitor (AMP) cells cultured from CD117 negative and CD90 negative freshly isolated AMP cells, wherein the spinal cord cells are selected from the group consisting of neurons, oligodendrocytes, astrocytes, microglial cells, and ependymal cells.

2. The method of claim 1 wherein the AMP cells are administered in combination with other agents and/or treatment modalities, wherein the other agents are selected from the group consisting of neuroregenerative agents, neuroprotective agents, neurotrophic factors, growth factors, cytokines, chemokines, antibodies, inhibitors, antibiotics, immunosuppressive agents, steroids, anti-fungals, anti-virals or other cell types, and the other treatment modality is therapeutic cooling, wherein the neuroprotective agent is dopamine D3 receptor agonists, the neurotrophic factors are selected from the group consisting of BDNF, NT-3, NT-4, CNTF, NGF, or GDNF;

the antibodies are IN-1 anti-NOGO antibodies;

the inhibitor is the PDE4 inhibitor rollipram;

the immunosuppressive agents are selected from the group consisting of corticosteroids, cyclosporine, tacrolimus, sirolimus, methotrexate, azathiopine, mercatopurine, cytotoxic antibiotics, anti-T-cell receptor (CD23) and anti-IL2 receptor (CD25) antibodies, interferon, opioids, TNF binding proteins, mycophenolate, and FTY720;

the antibiotics are selected from the group consisting of pikromycin, narbomycin, methymycin and neomethymycin;

the steroid is methylprednisolone; and

the other cell types are selected from the group consisting of differentiated amnion-derived multipotent progenitor cells, a mixture of differentiated and undifferentiated AMP cells, and a mixture of AMP cells and/or cells differentiated from AMP cells and neural stem cells.

3. A method for ameliorating scarring following spinal cord injury in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a composition comprising AMP cells cultured from CD117 negative and CD90 negative freshly isolated AMP cells.

4. The method of claim 3 wherein the AMP cells are administered in combination with other agents and/or treatment modalities, wherein the other agents are selected from the group consisting of neuroregenerative agents, neuroprotective agents, neurotrophic factors, growth factors, cytokines, chemokines, antibodies, inhibitors, antibiotics, immunosuppressive agents, steroids, anti-fungals, anti-virals or other cell types, and the other treatment modality is therapeutic cooling wherein the neuroprotective agent is dopamine D3 receptor agonists, the neurotrophic factors are selected from the group consisting of BDNF, NT-3, NT-4, CNTF, NGF, or GDNF;

the antibodies are IN-1 anti-NOGO antibodies;

the inhibitor is the PDE4 inhibitor rollipram;

the immunosuppressive agents are selected from the group consisting of corticosteroids, cyclosporine, tacrolimus, sirolimus, methotrexate, azathiopine, mercatopurine, cytotoxic antibiotics, anti-T-cell receptor (CD23) and anti-IL2 receptor (CD25) antibodies, interferon, opioids, TNF binding proteins, mycophenolate, and FTY720;

the antibiotics are selected from the group consisting of pikromycin, narbomycin, methymycin and neomethymycin;

the steroid is methylprednisolone; and

the other cell types are selected from the group consisting of differentiated amnion-derived multipotent progenitor cells, a mixture of differentiated and undifferentiated AMP cells, and a mixture of AMP cells and/or cells differentiated from AMP cells and neural stem cells.

5. A method for neuroprotecting spinal cord neurons following spinal cord injury in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a composition comprising AMP cells cultured from CD117 negative and CD90 negative freshly isolated AMP cells.

6. The method of claim 5 wherein the AMP cells are administered in combination with other agents and/or treatment modalities, wherein the other agents are selected from the group consisting of neuroregenerative agents, neuroprotective agents, neurotrophic factors, growth factors, cytokines, chemokines, antibodies, inhibitors, antibiotics, immunosuppressive agents, steroids, anti-fungals, anti-virals or other cell types, and the other treatment modality is therapeutic cooling wherein the neuroprotective agent is dopamine D3 receptor agonists, the neurotrophic factors are selected from the group consisting of BDNF, NT-3, NT-4, CNTF, NGF, or GDNF;

the antibodies are IN-1 anti-NOGO antibodies;

the inhibitor is the PDE4 inhibitor rollipram;

the immunosuppressive agents are selected from the group consisting of corticosteroids, cyclosporine, tacrolimus, sirolimus, methotrexate, azathiopine, mercatopurine, cytotoxic antibiotics, anti-T-cell receptor (CD23) and anti-IL2 receptor (CD25) antibodies, interferon, opioids, TNF binding proteins, mycophenolate, and FTY720;

the antibiotics are selected from the group consisting of pikromycin, narbomycin, methymycin and neomethymycin;

the steroid is methylprednisolone; and

the other cell types are selected from the group consisting of differentiated amnion-derived multipotent progenitor cells, a mixture of differentiated and undifferentiated AMP cells, and a mixture of AMP cells and/or cells differentiated from AMP cells and neural stem cells.