Cell Growth With Mechanical Stimuli

Abstract

Embodiments for loading and expanding particular cell types are described. Embodiments may include the use of hollow fiber membranes with particular characteristic such as hollow fibers with inner diameters that provide mechanical stimulus (e.g., radius of curvature greater than a dimension of a cell). In addition, embodiments may provide for manipulation of flow rates and other features that also provide mechanical stimuli and promote or enhance the growth of particular types of cells.

1 .- 20 . (canceled) 
     
     
         21 . A method of growing cells, the method comprising:
 circulating a first fluid through an intracapillary loop of a hollow fiber bioreactor at a first flow rate, the hollow fiber bioreactor being oriented at a first orientation, and the first fluid including cells;   maintaining the hollow fiber bioreactor at the first orientation for a first period of time;   rotating the hollow fiber bioreactor to a second orientation different from the first orientation;   maintaining the hollow fiber bioreactor at the second orientation for a second period of time; and   circulating media through the intracapillary loop at a second flow rate for a third period of time, the second flow rate being higher than the first flow rate,   wherein the hollow fiber bioreactor is configured to provide an environment to promote expansion of the cells during the third period of time.   
     
     
         22 . The method of  claim 21 , wherein the cells are endothelial cells. 
     
     
         23 . The method of  claim 21 , wherein the circulating the first fluid through the intracapillary loop includes flowing the first fluid into a hollow fiber of the hollow fiber bioreactor. 
     
     
         24 . The method of  claim 23 , further comprising:
 flowing a second fluid into the hollow fiber.   
     
     
         25 . The method of  claim 23 , further comprising:
 flowing a portion of the second fluid through a wall of the hollow fiber to move the cells toward an inside wall of the hollow fiber.   
     
     
         26 . The method of  claim 23 , wherein the first fluid is different from the second fluid. 
     
     
         27 . The method of  claim 21 , further comprising:
 rotating the hollow fiber bioreactor during the third period of time to promote expansion of the cells.   
     
     
         28 . The method of  claim 21 , wherein the second period of time occurs after the first period of time, and the third period of time occurs after the second period of time. 
     
     
         29 . A method of growing cells, the method comprising:
 circulating a first fluid through an intracapillary loop of a hollow fiber bioreactor, the hollow fiber bioreactor having a longitudinal axis;   maintaining the longitudinal axis of the hollow fiber bioreactor at a first position;   while maintaining the longitudinal axis of the hollow fiber bioreactor at the first position, circulating a second fluid through the intracapillary loop of the hollow fiber bioreactor; and   while circulating the second fluid through the intracapillary loop, passing a portion of the second fluid through a wall of the at least one of a plurality of hollow fibers of the hollow fiber bioreactor,   wherein the circulating the second fluid and the passing the portion of the second fluid through the wall moves the cells toward an inside wall of at least one of the plurality of hollow fibers and attaches at least a sub-portion of the cells to the inside wall of the at least one of the plurality of hollow fibers, and   wherein the first fluid is different from the second fluid.   
     
     
         30 . The method of  claim 29 , wherein the first position is at an angle greater than zero degrees from a substantially horizontal position. 
     
     
         31 . The method of  claim 29 , wherein, during the circulating the first fluid through the intracapillary loop of the hollow fiber bioreactor, introducing the first fluid comprising cells into an intracapillary space of each of the plurality of hollow fibers of the hollow fiber bioreactor. 
     
     
         32 . The method of  claim 29 , wherein the fluid includes endothelial cells. 
     
     
         33 . The method of  claim 29 , wherein the portion of the cells attaches to a lumen wall of the at least one of the plurality of hollow fibers.