Methods for cell mobilization using in vivo treatment with hyaluronan (ha)

Abstract

The use of forms of hyaluronic acid having a molecular weight less than about 750,000 daltons selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof is provided for the same purposes known for using recombinant GM-CSF or G-CSF.

1 - 206 . (canceled) 
   
   
       207 . A method for treating a patient having a condition characterized by a need for increased hematopoietic cells in the blood of the patient, consisting essentially of administering to the patient an effective amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof having a molecular weight of less than 750,000 daltons, wherein the administration of the form of hyaluronic acid causes mobilization of the hematopoietic cells-from bone marrow and other tissue sites into the blood of the patient. 
   
   
       208 . The method of  claim 207 , wherein the hematopoietic cells are stem cells 
   
   
       209 . The method of  claim 207 , wherein the condition is characterized by a need for increased red blood cells. 
   
   
       210 . The method of  claim 209 , wherein the administration of the form of hyaluronic acid causes mobilization of erythroblasts from bone marrow and other tissue sites into the blood of the patient in need of increased red blood cells. 
   
   
       211 . The method of  claim 209 , wherein the condition is an acquired anemia. 
   
   
       212 . The method of  claim 211 , wherein the acquired anemia is selected from iron deficient anemia, post-surgical anemia, infection-related anemia, insulin related anemia, low hemoglobin anemia of pregnancy, anemia from blood loss, anemia from poor red blood cell production, or anemia from red blood cell destruction. 
   
   
       213 . The method of  claim 207 , wherein the condition is characterized by a need for increased components of the acquired/adaptive immune response. 
   
   
       214 . The method of  claim 213 , wherein the administration of the form of hyaluronic acid causes mobilization of components of the acquired/adaptive immune response from bone marrow and other tissue sites into the blood of the patient in need of increased components of the acquired/adaptive immune response. 
   
   
       215 . The method of  claim 214 , wherein the administration of the form of hyaluronic acid causes mobilization of lymphocytes into the blood of the patient. 
   
   
       216 . The method of  claim 214 , wherein the administration of the form of hyaluronic acid causes mobilization of T cells into the blood of the patient. 
   
   
       217 . The method of  claim 214 , wherein the administration of the form of hyaluronic acid causes mobilization of B cells into the blood of the patient. 
   
   
       218 . The method of  claim 214 , wherein the administration of the form of hyaluronic acid causes mobilization of plasma cells into the blood of the patient. 
   
   
       219 . The method of  claim 214 , wherein the administration of the form of hyaluronic acid causes mobilization of polymorphonuclear cells into the blood of the patient. 
   
   
       220 . The method of  claim 214 , wherein the administration of the form of hyaluronic acid causes mobilization of granulocytes into the blood of the patient. 
   
   
       221 . The method of  claim 214 , wherein the administration of the form of hyaluronic acid causes mobilization of monocytes into the blood of the patient. 
   
   
       222 . The method of  claim 209 , wherein the administration of the form of hyaluronic acid once weekly for at least 4 weeks, causes mobilization of erythroblasts into the blood of the patient after administration of the form of hyaluronic acid in week 4. 
   
   
       223 . The method of  claim 222 , wherein the administration of the form of hyaluronic acid for at least causes mobilization of erythroblasts into the blood of the patient within about 4 hours after administration of the form of hyaluronic acid in week 4. 
   
   
       224 . The method of  claim 214 , wherein the condition is immunodeficiency in an AIDS patient. 
   
   
       225 . The method of  claim 224 , wherein the administration of the form of hyalouronic acid causes mobilization of B cells into the blood of the AIDS patient. 
   
   
       226 . The method of  claim 224 , wherein the administration of the form of hyalouronic acid causes mobilization of T cells from lymphoid organs and tissue into the blood of the AIDS patient. 
   
   
       227 . The method of  claim 226 , wherein the T cells are CD4+ T cells. 
   
   
       228 . The method of  claim 226 , wherein the lymphoid organs and tissue are spleen, lymph, Peyer's patches, gut-associated lymphoid tissue or skin associated lymphoid tissue. 
   
   
       229 . The method of  claim 207 , wherein the form of hyaluronic acid is sodium hyaluronate. 
   
   
       230 . The method of  claim 207 , wherein the form of hyaluronic acid has a molecular of between about 178,000 to about 562, 000, daltons 
   
   
       231 . The method of  claim 230 , wherein the form of hyaluronic acid has a molecular weight of about 320,000 daltons. 
   
   
       232 . The method of  claim 207 , wherein the form of hyaluronic acid has a molecular weight of 200,000 to 300,000 daltons. 
   
   
       233 . The method of  claim 232 , wherein the form of hyaluronic acid has a molecular weight of about 225,000 daltons 
   
   
       234 . The method of  claim 207 , wherein the form of hyaluronic acid has a molecular weight of 25,000 to 100,000 daltons. 
   
   
       235 . The method of  claim 207 , wherein the amount of the form of hyaluronic acid is at least about 6 mg/kg of patient body weight. 
   
   
       236 . The method of  claim 207 , wherein the amount of the form of hyaluronic acid is at least about 12 mg/kg of patient body weight. 
   
   
       237 . The method of  claim 207 , wherein a single dose of a form of hyaluronic acid is administered to the patient 
   
   
       238 . The method of  claim 207 , wherein a plurality of doses of a form of hyaluronic acid is administered to the patient 
   
   
       239 . The method of  claim 207 , consisting essentially of administering to the patient a plurality of dosages comprising:
 (a) a priming dosage of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof having a molecular weight less than about 750,000 daltons in an amount of less than about 3 mg/kg patient body weight, and following predetermined intervals, and   (b) one or more additional dosages of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof having a molecular weight less than about 750,000 daltons in an amount of at least about 1.5 mg/kg patient body weight,   
     wherein the administration of the plurality of dosages of a form of hyaluronic acid causes mobilization of the hematopoietic cells from bone marrow and other tissue sites into the blood of the patient. 
   
   
       240 . The method of  claim 239 , wherein the priming dosage is in the amount of 1.5 mg/kg patient body weight. 
   
   
       241 . The method of  claim 239 , wherein the additional dosage comprises a form of hyaluronic acid in the amount of at least about 6 mg/kg patient body weight. 
   
   
       242 . The method of  claim 239 , wherein additional dosages comprising 3 mg/kg patient body weight, 6 mg/kg patient body weight, and 12 mg/kg patient body weight are administered to the patient following weekly intervals. 
   
   
       243 . A method for treating a patient having a condition characterized by a need for increased hematopoietic cells in the blood of the patient, consisting essentially of administering to the patient an effective amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and pharmaceutically acceptable salts thereof, wherein the administration of the form of hyaluronic acid causes mobilization of the hematopoietic cells from bone marrow and other tissue sites into the blood of the patient.