Compositions for Cellular Restoration and Methods of Making and Using Same

Abstract

A method comprising obtaining a first cell sample from a first subject; obtaining a second cell sample from a second subject; culturing the first cell sample in the presence of at least a portion of a culture media of the second cell sample for a time period ranging from about 24 hours to about 6 weeks to produce a restoring composition; and contacting the restoring composition with the second cell sample for a period of time ranging from about 24 hours to about 6 weeks to produce a restored composition.

1 . A method comprising:
 (i) obtaining a first cell sample from a first subject;   (ii) obtaining a second cell sample from a second subject;   (iii) culturing the first cell sample in the presence of at least a portion of a culture media of the second cell sample for a time period ranging from about 24 hours to about 6 weeks to produce a restoring composition; and   (iv) contacting the restoring composition with the second cell sample for a period of time ranging from about 24 hours to about 6 weeks to produce a restored composition.   
     
     
         2 . The method of  claim 1  further comprising immunophenotyping the first cell sample, the second cell sample, the restored composition, or combinations thereof. 
     
     
         3 . The method of  claim 1  wherein the first subject, the second subject, or both are related by consanguinity. 
     
     
         4 . The method of  claim 1  wherein the first subject and the second subject differ in chronological age by from about 5 years to about 75 years. 
     
     
         5 . The method of  claim 1  wherein the second subject has a medical condition that is undiagnosed in the first subject. 
     
     
         6 . The method of  claim 1  wherein the first subject, the second subject, or both have been administered a mobilizer prior to step (i). 
     
     
         7 . The method of  claim 1  wherein the first cell sample and second cell sample comprise adult stem cells. 
     
     
         8 . The method of  claim 1  wherein the first cell sample and second cell sample exclude stem cells that are embryonic in origin. 
     
     
         9 . The method of  claim 1  wherein the first cell sample, the second cell sample, or both are obtained from a subject's peripheral blood. 
     
     
         10 . The method of  claim 1  wherein the first cell sample, the second cell sample, or both are harvested directly from a subject's bone marrow. 
     
     
         11 . The method of  claim 1  wherein the first cell sample, the second cell sample, or both comprise non-hematopoietic cells, mesenchymal stem cells, endothelial progenitor cells, hematopoietic stem cells, primitive hematopoietic stem cells, hematopoietic progenitor cells, differentiated hematopoietic cells, T-lymphocytes, natural killer cells, or combinations thereof. 
     
     
         12 . The method of  claim 1  wherein the first cell sample, the second cell sample, or both comprise non-senescent and senescent cells. 
     
     
         13 . The method of  claim 12  wherein the non-senescent cells are present in an amount of from about 90% to about 99% based on the total cell number. 
     
     
         14 . The restoring composition of  claim 1 . 
     
     
         15 . A kit comprising the restoring composition of  claim 1 . 
     
     
         16 . A method comprising administering to a subject an effect amount of the restoring composition of  claim 1 . 
     
     
         17 . A pharmaceutical formulation comprising the restoring composition of  claim 1  and an active selected from the group consisting of antimicrobials, steroids, pain medications, anti-inflammatory agents, growth factors, cytokines, hormones, and combinations thereof. 
     
     
         18 . An exosome isolated from the restoring composition of  claim 1 . 
     
     
         19 . A microvesicle isolated from the restoring composition of  claim 1 . 
     
     
         20 . A kit comprising a microvesicle isolated from the restoring composition of  claim 1 . 
     
     
         21 . A kit comprising an exosome isolated from the restoring composition of  claim 1 . 
     
     
         22 . A method comprising administering to a subject an effect amount of an exosome isolated from the restoring composition of  claim 1 . 
     
     
         23 . A method comprising administering to a subject an effect amount of a microvesicle isolated from the restoring composition of  claim 1 . 
     
     
         24 . A pharmaceutical formulation comprising an exosome isolated from the restoring composition of  claim 1  and an active selected from the group consisting of antimicrobials, steroids, pain medications, anti-inflammatory agents, growth factors, cytokines, hormones, and combinations thereof. 
     
     
         25 . A pharmaceutical formulation comprising a microvesicle isolated from the restoring composition of  claim 1  and an active selected from the group consisting of antimicrobials, steroids, pain medications, anti-inflammatory agents, growth factors, cytokines, hormones, and combinations thereof. 
     
     
         26 . A plurality of exosomes isolated from the restoring composition of  claim 1 . 
     
     
         27 . A plurality of microvesicles isolated from the restoring composition of  claim 1 . 
     
     
         28 . A cell free media prepared by filtration of the restoring composition of  claim 1  wherein the cell free media comprise extracellular vesicles. 
     
     
         29 . A method comprising contacting a receiver cell sample with a donor cell sample to produce a restored composition wherein the restored composition has an innate immune function as determined by a natural killer cell assay that is increased when compared to the innate immune function of the receiver cell sample and wherein the addition of mannumycin A to the donor cell sample prior to contact with the receiver cell sample inhibits the increase in innate immune function of the restored composition.