Cell delivery matrices
Cell delivery matrices and methods for facilitating local delivery of adipose derived endothelial cells to a target tissue, body cavity, or joint are described. The cell delivery matrix may be a three-dimensional matrix scaffold comprising fibrin derived from the patient's own body. The cell delivery matrix may be biocompatible and semi-permeable. The cell delivery matrix used in the methods of the invention may be comprised of any degradable, bioabsorbable or non-degradable, biocompatible polymer. Regenerative therapies comprising implanting in the subject cell delivery matrices localizing adipose derived endothelial cells are described. The cell delivery matrices maintain the adipose derived endothelial cells at the target for a therapeutically effective amount of time. The adipose derived endothelial cells can be allogenic or syngenic to the subject. The endothelial cells may be delivered alone or in combination with other therapeutic agents.
1 . A composition comprising a three-dimensional bio-compatible cell delivery matrix and endothelial cells, the matrix configured to localize the endothelial cells and to maintain the endothelial cells at a target of a subject for a therapeutically effective amount of time.
2 . The composition of claim 1 , the matrix comprising fibrin.
3 . The composition of claim 1 , the matrix comprising collagen.
4 . The composition of claim 1 , the matrix comprising a polymer.
5 . The composition of claim 4 , wherein the polymer is expanded polytetrafluoroethylene.
6 . The composition of claim 4 , wherein the polymer is polyethyleneterephthalate.
7 . The composition of claim 1 , wherein the endothelial cells are allogenic to the subject.
8 . The composition of claim 1 , wherein the endothelial cells are syngenic to the subject.
9 . A method for preparing a cell delivery matrix comprising:
providing a collecting vessel for processing tissue to produce an endothelial cell product, the vessel having a rinsing and digesting chamber in fluid communication with a separate waste chamber and an isolation chamber connected to the rinsing and digesting chamber, wherein a screen separates at least the rinsing and digesting chamber and the waste chamber;
introducing tissue to be processed into the rinsing and digesting chamber;
introducing rinsing solution into the rinsing and digesting chamber;
orienting the vessel to screen the tissue to be processed of rinsing solution passed into the waste chamber;
introducing an enzyme into the rinsing and digesting chamber;
heating the tissue and the enzyme for a sufficient time and temperature while agitating the rinsing and digesting chamber to digest the tissue with the enzyme;
centrifuging the vessel to transfer cells from the digested tissue from the rinsing and digesting chamber into the isolation chamber;
isolating the cells as a pellet of microvessel endothelial cells; and
enveloping the pellet of microvessel endothelial cells with a matrix.
10 . The method of claim 9 , wherein the matrix comprises fibrin.
11 . The method of claim 9 , wherein the matrix comprises collagen.
12 . The method of claim 9 , wherein the matrix comprises a polymer.
13 . The method of claim 12 , wherein the polymer is expanded polytetrafluoroethylene.
14 . The method of claim 12 , wherein the polymer is polyethyleneterephthalate.
15 . The method of claim 9 , wherein the endothelial cells are allogenic to the subject.
16 . The method of claim 9 , wherein the endothelial cells are syngenic to the subject.
17 . A method of delivering and maintaining stem cells at the lumenal surface of a tubular tissue, comprising:
providing a collecting vessel for processing tissue to produce an endothelial cell product, the vessel having a rinsing and digesting chamber in fluid communication with a separate waste chamber and an isolation chamber connected to the rinsing and digesting chamber, wherein a screen separates at least the rinsing and digesting chamber and the waste chamber;
introducing tissue to be processed into the rinsing and digesting chamber;
introducing rinsing solution into the rinsing and digesting chamber;
orienting the vessel to screen the tissue to be processed of rinsing solution passed into the waste chamber;
introducing an enzyme into the rinsing and digesting chamber;
heating the tissue and the enzyme for a sufficient time and temperature while agitating the rinsing and digesting chamber to digest the tissue with the enzyme;
centrifuging the vessel to transfer cells from the digested tissue from the rinsing and digesting chamber into the isolation chamber;
isolating the cells as a pellet of microvessel endothelial cells;
enveloping the pellet of microvessel endothelial cells with a cell delivery matrix; and
locally delivering the cells to a target.
18 . The method of claim 17 , wherein the cells are delivered to the target using balloon angioplasty.
19 . The method of claim 17 , wherein the cells are delivered to the target using a sustained low pressure sodding technique.
20 . A method of delivering a matrix to the lumenal surface of a tubular tissue, comprising:
providing a catheter having a proximal end and a distal end, defining a lumen therebetween, the proximal end of said catheter comprising a fluid reservoir, the distal end of said catheter comprising an expandable balloon having a plurality of apertures;
filling the fluid reservoir with the matrix and fluid;
applying pressure to proximal end of the catheter;
advancing the cells from the fluid reservoir to the lumen of the catheter;
expanding the balloon proximate the luminal surface of the tubular tissue;
delivering the matrix and fluid through the apertures of the balloon to the luminal surface of the tubular tissue;
sustaining the pressure on the balloon, thereby maintaining a pressure gradient between the lumen of the catheter and the luminal surface of the tubular tissue and advancing the matrix from the lumen of the catheter onto the luminal surface of the tubular tissue;
releasing the pressure on the lumen of the catheter; and
deflating the balloon.
21 . The method of claim 20 , wherein the matrix comprises fibrin.
22 . The method of claim 20 , wherein the matrix is coupled to endothelial cells.