Process for producing a tissue transplant construct for reconstructing a human or animal organ
AssigneeUroTec GmbH
InventorsGouya Ram-Liebig, Ursula Ravens, Manfred Wirth
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Abstract
A process for producing a tissue transplant construct for reconstructing a human or animal organ. The process may include the steps of: (a) isolation and two-dimensional cultivation of organ-specific tissue cells; (b) application of the organ-specific tissue cells to a biocompatible, collagen-containing membrane; and, (c) cultivation of the organ-specific tissue cells on the membrane with biochemical and mechanical stimulation of the organ-specific tissue cells. Tissue transplant constructs and methods for using tissue transplant constructs are also taught.
Claims31
1-26. (canceled)
A process for producing a tissue transplant construct for reconstructing a human or animal organ, comprising the steps
- (a) isolation and two-dimensional cultivation of organ-specific tissue cells;
- (b) application of the organ-specific tissue cells to a biocompatible, collagen-containing membrane;
- and
- (c) cultivation of the organ-specific tissue cells on the membrane with biochemical and mechanical stimulation of the organ-specific tissue cells.
The process as claimed in claim 1, wherein the tissue cells are muscle tissue cells.
The process as claimed in claim 2, wherein the muscle tissue cells are muscle tissue cells of a urinary bladder.
The process as claimed in claim 2, wherein the muscle tissue cells are cultivated with mitogenic stimulation after they have been applied to the membrane.
The process as claimed in claim 4, wherein the muscle tissue cells which are applied to the membrane are muscle tissue cells of passages 2 to 7 cultivated with mitogenic stimulation.
The process as claimed in claim 4, wherein the muscle tissue cells are cultivated muscle tissue cells of passages 3 to 6.
The process as claimed in claim 3, wherein cultivation of the muscle tissue cells in step (c) takes place with urothelial induction using a medium which has been conditioned by means of urothelium.
The process as claimed in claim 7, wherein the urothelium conditioning the medium is selected from the group consisting of proliferating urothelium and terminally differentiated urothelium.
The process as claimed in claim 8, wherein the urothelium is derived from the mucosal layer of the urinary bladder.
The process as claimed in claim 7, wherein the medium further comprises serum selected from the group consisting of fetal bovine serum (FCS) and autologous serum.
The process as claimed in claim 10, wherein the medium comprises the concentration of serum is about 5%.
The process as claimed in claim 11, wherein the concentration of serum is reduced stepwise to 0% during the cultivation of the muscle tissue cells on the membrane.
The process as claimed in claim 3, wherein the mechanical stimulation in step (c) comprises stretching of the membrane onto which the tissue cells are applied.
The process as claimed in claim 13, wherein the mechanical stimulation comprises
- (c1) stretching of the membrane for a preset period;
- (c2) relaxation of the membrane for a preset period;
- and
- (c3) n-fold repetition of steps (c1) and (c2), where n is an integer greater than or equal to 1.
The process as claimed in claim 14, wherein the membrane is stretched along its long axis.
The process as claimed in claim 15, wherein the cultivation of the muscle tissue cells in step (c) takes place with urothelial induction using a medium which has been conditioned by means of urothelium, and the urothelium are derived from a different urinary bladder as the muscle tissue cells.
The process as claimed in claim 15, wherein the cultivation of the muscle tissue cells in step (c) takes place with urothelial induction using a medium which has been conditioned by means of urothelium, wherein the muscle tissue cells and the urothelium are derived from the same urinary bladder.
The process as claimed in any of claim 15, wherein the muscle tissue cells are selected from the group consisting of smooth muscle cells, interstitial fibroblastic cells.
The process as claimed in claim 15, wherein the muscle tissue cells comprise smooth muscle cells and interstitial fibroblastic cells.
A tissue transplant construct for reconstructing a human or animal organ, comprising
- (a) a biocompatible, collagen-containing membrane;
- and
- (b) organ-specific tissue cells which have been cultivated on the membrane with biochemical and mechanical stimulation and which have been biochemically and mechanically stimulated.
The tissue transplant construct as claimed in claim 20, obtained by a process comprising the steps of:
- (a) isolation and two-dimensional cultivation of organ-specific tissue cells;
- (b) application of the organ-specific tissue cells to the biocompatible, collagen-containing membrane;
- and
- (c) cultivation of the organ-specific tissue cells on the membrane with biochemical and mechanical stimulation of the organ-specific tissue cells.
The tissue transplant construct as claimed in claim 21 for reconstructing a human or animal urinary bladder, wherein the organ-specific tissue cells are muscle tissue cells of a urinary bladder.
The tissue transplant construct as claimed in claim 22, wherein the muscle tissue cells of the urinary bladder are selected from the group consisting of smooth muscle cells, interstitial fibroblastic cells and mixtures thereof.
The tissue transplant construct as claimed in claim 21 wherein the muscle tissue cells are cultivated with mitogenic stimulation after they have been applied to the membrane.
The tissue transplant construct as claimed in claim 24
- wherein cultivation of the muscle tissue cells in step (c) takes place with urothelial induction using a medium which has been conditioned by means of urothelium.
The tissue transplant construct as claimed in claim 25, wherein the mechanical stimulation in step (c) comprises stretching of the membrane onto which the tissue cells are applied.
The tissue transplant construct as claimed in claim 26, wherein the urothelium conditioning the medium is selected from the group consisting of proliferating urothelium and terminally differentiated urothelium.
A method of reconstructing a human or animal organ comprising the steps of:
- (a) producing a tissue transplant construct, comprising
- (i) a biocompatible, collagen-containing membrane;
- and
- (ii) organ-specific tissue cells which have been cultivated on the membrane with biochemical and mechanical stimulation and which have been biochemically and mechanically stimulated.
- (b) reconstructing a human or animal organ.
Dependencies are inferred from the claim text.