Treatment of stroke using isolated placental cells

Abstract

Provided herein are methods for the treatment of stroke comprising administering to a stroke victim placental stem cells, populations of cells comprising placental stem cells, and/or compositions comprising placental stem cells.

What is claimed is: 
     
         1 . A method of treating an individual having a disruption in the flow of blood in or around the brain, comprising administering to said individual an effective amount of isolated human adherent placental cells that are:
 CD10 + , CD34 − , and CD105 + ;   CD200 +  and HLA-G + ;   CD73 + , CD105 + , and CD200 + ;   CD200 +  and OCT-4 + ;   CD73 + , CD105 +  and HLA-G + ;   CD73 +  and CD105 +  and facilitate the formation of one or more embryoid-like bodies in a population of placental cells comprising said stem cell when said population is cultured under conditions that allow the formation of an embryoid-like body; or   OCT-4 +  and facilitate the formation of one or more embryoid-like bodies in a population of placental cells comprising the stem cell when said population is cultured under conditions that allow formation of embryoid-like bodies; or any combination thereof.   
     
     
         2 . The method of  claim 1 , wherein said CD10 + , CD34 − , CD105 +  cells are additionally CD200 + . 
     
     
         3 . The method of  claim 2 , wherein said CD10 + , CD34 − , CD105 + , CD200 +  cells are additionally CD45 −  or CD90 + . 
     
     
         4 . The method of  claim 3 , wherein said CD10 + , CD34 − , CD105 + , CD200 +  cells are additionally CD45 −  and CD90 + . 
     
     
         5 . The method of  claim 1 , wherein said therapeutically effective amount is a number of said cells that results in elimination of, a detectable improvement in, lessening of the severity of, or slowing of the progression of one or more symptoms of disruption in the flow of blood in or around the brain exhibited by said individual. 
     
     
         6 . The method of  claim 5 , wherein said symptom is hemiplegia or hemiparesis. 
     
     
         7 . The method of  claim 5 , wherein said symptom is muscle weakness of the face; numbness; reduction in sensation; altered smell, taste, hearing, or vision; loss of smell, taste, hearing, or vision; drooping of an eyelid (ptosis); detectable weakness of an ocular muscle; decreased gag reflex; decreased ability to swallow; decreased pupil reactivity to light; decreased sensation of the face; decreased balance; nystagmus; altered breathing rate; altered heart rate; weakness in sternocleidomastoid muscle with decreased ability or inability to turn the head to one side; weakness in the tongue; aphasia (inability to speak or understand language); apraxia (altered voluntary movements); a visual field defect; a memory deficit; hemineglect or hemispatial neglect (deficit in attention to the space on the side of the visual field opposite the lesion); disorganized thinking; confusion; development of hypersexual gestures; anosognosia (persistent denial of the existence of a deficit); difficulty walking; altered movement coordination; vertigo; disequilibrium; loss of consciousness; headache; or vomiting, wherein said symptom is caused by disruption in the flow of blood in or around the brain. 
     
     
         8 . The method of  claim 1 , wherein said isolated human adherent placental cells are CD10 + , CD34 − , CD105 + , CD200 + . 
     
     
         9 . The method of  claim 8 , wherein said isolated human adherent placental cells are additionally CD45 −  and CD90 + . 
     
     
         10 . The method of  claim 1 , wherein said isolated human adherent placental cells are CD200 +  and HLA-G + . 
     
     
         11 . The method of  claim 10 , wherein said CD200 + , HLA-G +  cells are additionally CD34 − , CD38 − , CD45 − , CD73 +  and CD105 + . 
     
     
         12 . The method of  claim 1 , wherein said isolated human adherent placental cells are CD73 + , CD105 +  and HLA-G + . 
     
     
         13 . The method of  claim 11 , wherein said CD73 + , CD105 +  and HLA-G +  cells are additionally CD34 − , CD45 − , OCT-4 +  and CD200 + . 
     
     
         14 . The method of  claim 1 , wherein said CD73 + , CD105 + , and CD200 +  cells are additionally CD34 − , CD38 − , CD45 − , and HLA-G + . 
     
     
         15 . The method of  claim 1 , wherein said CD200 + , OCT-4 +  cells are additionally CD34 − , CD38 − , CD45 − , CD73 + , CD105 +  and HLA-G + . 
     
     
         16 . The method of  claim 1 , wherein said CD73 +  and CD105 +  cells are additionally OCT-4 + , CD34 − , CD38 −  and CD45 − . 
     
     
         17 . The method of  claim 1 , wherein said OCT-4 +  cells are additionally CD73 + , CD105 + , CD200 + , CD34 − , CD38 − , and CD45 − . 
     
     
         18 . The method of  claim 1 , wherein said isolated human adherent placental cells are contained within a population of cells, at least 80% of which are isolated human adherent placental cells. 
     
     
         19 . The method of  claim 1 , wherein said isolated human adherent placental cells are contained within a population of cells, at least 90% of which are said isolated human adherent placental cells. 
     
     
         20 . A method of treating an individual having a disruption in the flow of blood in or around the brain, comprising administering to said individual an effective amount of isolated human adherent placental cells, wherein said cells express one or more genes at a detectably higher level than a bone marrow-derived mesenchymal stem cell,
 wherein said one or more genes are one or more of ACTG2, ADARB1, AMIGO2, ARTS-1, B4GALT6, BCHE, C11orf9, CD200, COL4A1, COL4A2, CPA4, DMD, DSC3, DSG2, ELOVL2, F2RL1, FLJ10781, GATA6, GPR126, GPRC5B, ICAM1, IER3, IGFBP7, IL1A, IL6, IL18, KRT18, KRT8, LIPG, LRAP, MATN2, MEST, NFE2L3, NUAK1, PCDH7, PDLIM3, PKP2, RTN1, SERPINB9, ST3GAL6, ST6GALNAC5, SLC12A8, TCF21, TGFB2, VTN, and ZC3H12A, and   wherein said bone marrow-derived stem cell has undergone a number of passages in culture that is equivalent to the number of passages said placental stem cell has undergone.   
     
     
         21 . The method of  claim 1 , wherein said disruption of the flow of blood is stroke. 
     
     
         22 . The method of  claim 21 , wherein said stroke is ischemic stroke. 
     
     
         23 . The method of  claim 21 , wherein said stroke is hemorrhagic stroke. 
     
     
         24 . The method of  claim 1 , wherein said disruption is a hematoma. 
     
     
         25 . The method of  claim 24 , wherein said hematoma is a dural hematoma, a subdural hematoma, or a subarachnoid hematoma. 
     
     
         26 . The method of  claim 1 , wherein said disruption is vasospasm. 
     
     
         27 . The method of  claim 1 , wherein said isolated placental cells are administered by bolus injection. 
     
     
         28 . The method of  claim 1 , wherein said isolated placental cells are administered by intravenous infusion. 
     
     
         29 . The method of  claim 1 , wherein said isolated placental cells are administered intracranially. 
     
     
         30 . The method of  claim 29 , wherein said isolated placental cells are administered within an area of ischemia. 
     
     
         31 . The method of  claim 29 , wherein said isolated placental cells are administered to an area peripheral to an ischemia. 
     
     
         32 . The method of  claim 1 , wherein said isolated placental cells are administered intraperitoneally, intramuscularly, intradermally or intraocularly. 
     
     
         33 . The method of  claim 1 , wherein said isolated adherent placental cells are administered by surgical implantation of a composition comprising said isolated human adherent placental cells. 
     
     
         34 . The method of  claim 33 , wherein said composition is a matrix or scaffold. 
     
     
         35 . The method of  claim 34 , wherein said matrix or scaffold is a hydrogel. 
     
     
         36 . The method of  claim 34 , wherein said matrix or scaffold is a decellularized tissue. 
     
     
         37 . The method of  claim 34 , wherein said matrix or scaffold is a synthetic biodegradable composition. 
     
     
         38 . The method of  claim 1 , wherein said isolated placental cells are administered once to said individual. 
     
     
         39 . The method of  claim 1 , wherein said isolated placental cells are administered to said individual a plurality of times. 
     
     
         40 . The method of  claim 1 , wherein said administering comprises administering between about 1×10 4  and 1×10 5  isolated placental cells per kilogram of said individual. 
     
     
         41 . The method of  claim 1 , wherein said administering comprises administering between about 1×10 5  and 1×10 6  isolated placental cells per kilogram of said individual. 
     
     
         42 . The method of  claim 1 , wherein said administering comprises administering between about 1×10 6  and 1×10 7  isolated placental cells per kilogram of said individual. 
     
     
         43 . The method of  claim 1 , wherein said administering comprises administering between about 1×10 7  and 1×10 8  isolated placental cells per kilogram of said individual. 
     
     
         44 . The method of  claim 1 , wherein said administering comprises administering between about 5×10 7  and 3×10 9  isolated placental cells intravenously. 
     
     
         45 . The method of  claim 44 , wherein said administering comprises administering about 9×10 8  isolated placental cells. 
     
     
         46 . The method of  claim 44 , wherein said administering comprises administering about 1.8×10 9  isolated placental cells. 
     
     
         47 . The method of  claim 1 , wherein said administering comprises administering between about 5×10 7  and 1×10 8  isolated placental cells intracranially. 
     
     
         48 . The method of  claim 47 , wherein said administering comprises administering about 9×10 7  isolated placental cells. 
     
     
         49 . The method of  claim 1 , comprising administering a second therapeutic agent to said individual. 
     
     
         50 . The method of  claim 49 , wherein said second therapeutic agent is a neuroprotective agent. 
     
     
         51 . The method of  claim 50 , wherein said second therapeutic agent is NXY-059 (disulfonyl derivative of phenylbutylnitrone). 
     
     
         52 . The method of  claim 49 , wherein said second therapeutic agent is a thrombolytic agent. 
     
     
         53 . The method of  claim 52 , wherein said thrombolytic agent is tissue plasminogen activator (tPA). 
     
     
         54 . The method of  claim 1 , wherein said isolated placental cells are administered to said individual within 48 hours of development of one or more symptoms of disruption of blood flow in or around the brain in said individual. 
     
     
         55 . The method of  claim 1 , wherein said isolated placental cells are administered to said individual within 24 hours of development of one or more symptoms of disruption of blood flow in or around the brain in said individual. 
     
     
         56 . The method of  claim 1 , wherein said isolated placental cells are administered to said individual within 12 hours of development of one or more symptoms of disruption of blood flow in or around the brain in said individual. 
     
     
         57 . The method of  claim 1 , wherein said isolated placental cells are administered to said individual within 3 hours of development of one or more symptoms of disruption of blood flow in or around the brain in said individual. 
     
     
         58 . The method of  claim 1 , wherein said isolated placental cells were cryopreserved prior to said administering. 
     
     
         59 . The method of  claim 1 , wherein said isolated human adherent placental cells are obtained from a placental stem cell bank. 
     
     
         60 . The method of  claim 20 , wherein said isolated human adherent placental cells express said one or more genes when cultured for about 3 to about 35 population doublings in a medium comprising 60% DMEM-LG and 40% MCDB-201; 2% fetal calf serum; 1× insulin-transferrin-selenium (ITS); 1× linoleic acid-bovine serum albumin (LA-BSA); 10 −9  M dexamethasone; 10 −4  M ascorbic acid 2-phosphate; epidermal growth factor 10 ng/mL; and platelet-derived growth factor (PDGF-BB) 10 ng/mL. 
     
     
         61 . The method of  claim 20  wherein said isolated human adherent placental cells express said one or more genes when cultured for from about 3 to about 35 population doublings in a medium comprising 60% DMEM-LG (Gibco) and 40% MCDB-201 (Sigma); 2% fetal calf serum (Hyclone Labs.); 1× insulin-transferrin-selenium (ITS); 1× linoleic acid-bovine serum albumin (LA-BSA); 10 −9  M dexamethasone (Sigma); 10 −4  M ascorbic acid 2-phosphate (Sigma); epidermal growth factor 10 ng/mL (R&D Systems); and platelet-derived growth factor (PDGF-BB) 10 ng/mL (R&D Systems).