JP2007229250A - Method of releasing cell sheet - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To facilitate the repair of an affected site by reliably releasing a cell sheet in the neighborhood of the affected site in a body cavity. <P>SOLUTION: In a method of releasing the cell sheet 1, the cell sheet 1 is pushed out of the tube 4 by a pressing means 5 guided from the back of the tube 4 which houses the cell sheet 1 rolled in a cylindrical shape with the adhesive surface 1a facing inwardly in the radial direction and has the distal end placed in the neighborhood of the affected area A. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a cell sheet release method.

  Conventionally, cultured epithelial cell sheets have been used for the treatment of moderate or severe corneal diseases such as scar keratoconjunctivitis (see, for example, Patent Document 1). Further, in order to treat skin damage such as burns, cell sheets are used to remove epidermis killed by burns and mask the removed portions (see, for example, Patent Document 2). Since these cell sheets are manufactured by collecting and culturing normal cells of the patient himself, there is an advantage that there is no problem such as immune rejection.

  Patent Document 2 discloses a method of using a culture vessel whose surface is coated with a temperature-responsive polymer as a method for producing a cell sheet. A temperature-responsive polymer has a property of rapidly changing from hydrophobic to hydrophilic depending on temperature. For example, when cultured at 37 ° C., it exhibits hydrophobicity and grows while maintaining adherent cells in an adhesive state. When promoting and exfoliating, for example, by cooling to about 20 ° C., it becomes hydrophilic and cells can be easily exfoliated from the culture vessel.

Advantages of using a temperature-responsive polymer to produce a healthy cell sheet with less damage to cells compared to the case of exfoliation using a conventional proteolytic enzyme such as trypsin. There is.
And since the cell sheet peeled in this way is peeled by the action of the temperature-responsive polymer provided on the bottom surface of the culture vessel, there is no change in the adhesion of the cell itself, Can be used for masking or the like by pasting the surface adhered to the culture vessel on the affected area as an adhesive surface.
JP 2002-331005 A International Publication No. 02/10349 Pamphlet

  However, in the treatment of a portion exposed to the outside of the human body, such as the treatment of corneal disease described above or the treatment of skin at the time of a burn, the adhesive surface of the cell sheet is spread so as not to adhere to other portions. Can be easily placed on the affected area, but for example, to place a cell sheet on an ulcer formed in the inner wall of the esophagus, stomach or intestine, or on a site where the mucosa has been resected endoscopically, It is necessary to insert a cell sheet via an elongated body cavity in a targeted or transanal manner and release it near the affected area.

  The present invention has been made in view of the above-described circumstances, and it is an object of the present invention to provide a cell sheet release method that reliably releases a cell sheet in the vicinity of an affected part in a body cavity and facilitates repair of the affected part. It is said.

In order to achieve the above object, the present invention provides the following means.
The present invention accommodates a cell sheet rolled in a cylindrical shape with the adhesive surface facing radially inward, and the cell sheet is removed from the tube by pressing means guided from the rear of the tube with the tip disposed in the vicinity of the affected part. A method for releasing extruded cell sheets is provided.

  According to the present invention, the cell sheet is held in an accommodation state without being adhered to the inner wall surface of the tube by rolling the adhesion surface in a cylindrical shape inward in the radial direction. Therefore, it can be easily pushed out from the distal end of the tube into the body cavity and released simply by pressing the cell sheet with a pressing means guided from the rear of the tube, for example, a liquid such as water or a wire.

In the said invention, it is preferable to extrude in the state which faced the cut | interruption of the cell sheet rounded to the said cylinder shape to the adhesion | attachment site | part.
In this way, when the cell sheet is released from inside the tube, it spreads from the cut side and returns to a substantially flat form, so that the spread cell sheet can be quickly applied to the adhesion site without changing the posture. Can do.

  In addition, the present invention accommodates a cell sheet member in which a tubular spacer made of a biocompatible material having a predetermined thickness is attached to the outer peripheral portion of an adhesive surface of a cell sheet shaped into a circle, and the tip is an affected part. There is provided a cell sheet releasing method for pushing out a cell sheet member from a tube by a pressing means guided from behind a tube arranged in the vicinity.

  According to the present invention, by using a cell sheet member in which a tubular spacer is bonded to the outer peripheral portion of the bonding surface of the cell sheet, the cell sheet can be held in an accommodation state without being bonded to the inner wall surface of the tube. Therefore, the cell sheet member can be easily pushed out from the distal end of the tube into the body cavity and released simply by pressing the cell sheet member with the pressing means guided from the rear of the tube.

  Furthermore, the present invention cools the temperature-responsive member in the vicinity of the affected area in a state where a temperature-responsive member having temperature responsiveness that switches between hydrophilicity and hydrophobicity depending on the temperature is adhered to the adhesive surface of the cell sheet. A cell sheet release method is provided.

  According to the present invention, by setting the temperature-responsive member to the cell sheet adhesive surface, the cell sheet adhesive surface can be disposed in the vicinity of the affected part in the body cavity without adhering to the surrounding body cavity inner wall or the like. Then, by cooling there, the temperature-responsive member can be switched to hydrophilic, the cell sheet can be peeled off, and can be easily released near the affected area.

In the above invention, the temperature-responsive member may be in the form of a sheet.
By doing in this way, it becomes possible to release the cell sheet in the vicinity of the affected part, and the adhesion work to the affected part can be facilitated.

Moreover, in the said invention, the said temperature-responsive member is good also as being comprised by the member which can deform | transform.
By doing this, in a narrow body cavity from the mouth or anus to the vicinity of the affected area, the temperature responsive member to which the cell sheet is adhered is deformed thinly, and the temperature responsive member is deformed to be expanded in the vicinity of the affected area. By this, it becomes possible to release the cell sheet in an expanded state, and the adhesion work to the affected part can be facilitated.

Further, in the above invention, the temperature responsive member may include a shape memory actuator.
By doing in this way, a temperature change can be given to a shape memory actuator, and it can change to a desired form easily. Shape memory actuators include shape memory alloys or shape memory polymers.

In the invention described above, the temperature-responsive member may be a metal stent.
In this way, by releasing the metal stent in the vicinity of the affected area or by inflating a balloon disposed inside the metal stent, the cell sheet is expanded to a shape suitable for the affected area, and the metal stent is cooled in that state. By doing so, the cell sheet can be released.

In the above invention, the temperature-responsive member may be a balloon.
By doing so, the cell sheet can be released by inflating the balloon in the vicinity of the affected area, expanding the cell sheet into a shape suitable for the affected area, and cooling the balloon in that state.

  According to the present invention, it is possible to reliably release a cell sheet in the vicinity of an affected part in a body cavity and facilitate repair of the affected part.

Hereinafter, a method for releasing the cell sheet 1 according to the first embodiment of the present invention will be described below with reference to FIG.
As shown in FIG. 1, the cell sheet 1 release method according to the present embodiment is a flexible material having an outer diameter dimension that can be inserted into a channel 3 provided along the longitudinal direction of the insertion portion 2 of the endoscope. This is a method of releasing the cell sheet 1 accommodated at the tip of the tube 4.

  The cell sheet 1 is obtained, for example, by collecting oral mucosa and culturing it in a culture container (not shown) having a temperature-responsive treatment on the bottom surface. The temperature-responsive treatment is, for example, applied with a polymer made of N-isopropylacrylamide, and exhibits hydrophobicity at 32 ° C. or higher and hydrophilicity at a temperature lower than 32 ° C.

  At the time of culture, for example, since the culture vessel is cultured at 37 ° C., the bottom surface of the culture vessel has sufficient hydrophobicity, and the squamous epithelial cells constituting the oral mucosa can easily adhere to the bottom surface of the culture vessel and grow. Can do. On the other hand, at the end of the culture, by cooling to a temperature lower than 32 ° C., the bottom surface of the culture vessel rapidly becomes hydrophilic, and the cultured squamous epithelial cells can be easily detached.

  In the present embodiment, for example, a rectangular sheet is illustrated as the cell sheet 1, but the present invention is not limited to this, and any form such as a polygon, a circle, an ellipse, or the like is not limited to this. The cell sheet 1 can be employed.

  The squamous epithelial cells peeled off from the bottom surface of the culture vessel are peeled off while adhering to the bottom surface of the culture vessel and growing, so that the single cell sheet 1 is formed. The back side of the cell sheet 1 that has been adhered to the bottom surface of the culture container continues to have adhesiveness even after peeling, and the front side has no adhesiveness.

  Therefore, in the present embodiment, the cell sheet 1 is formed in a cylindrical shape with the adhesive surface (hereinafter referred to as an adhesive surface) 1a of the manufactured cell sheet 1 facing inward in the radial direction. The cell sheet 1 is housed inside the tip of the tube 4. In this state, since the bonding surface 1a is directed inward in the radial direction, the cell sheet 1 is held in a state of being pressed against the inner surface of the tube 4 by its elasticity without being bonded to the inner surface of the tube 4.

  Depending on the position of the affected part A to which the cell sheet 1 is applied, the cell sheet 1 is accommodated via the channel 3 provided in the insertion part 2 of the endoscope that is inserted orally or transanally. The tube 4 is inserted from the distal end side, and the distal end of the tube 4 is projected from the distal end of the insertion portion 2. The position of the affected area A can be easily identified by endoscopy, and the distal end position of the tube 4 is arranged at a position in the vicinity of the identified affected area A.

  The cell sheet 1 releasing method according to the present embodiment is such that the cell sheet 1 in the tube 4 is pressed by the pressing means 5 introduced from the rear of the tube 4 in this state and pushed out from the tip of the tube 4. As the pressing means 5, for example, a device that presses and extrudes the cell sheet 1 with a liquid such as a wire or water is employed.

According to the release method according to the present embodiment, the adhesive surface 1a is held inward in the radial direction so that the cell sheet 1 does not adhere to the inner surface of the tube 4, so that it is easily pushed out by the operation of the pressing means 5. Thus, it can be reliably released in the vicinity of the affected area A.
In this case, as shown in FIGS. 1A and 1B, the cell sheet 1 is preferably pushed out from the tube 4 so that the cut line 1 b when rolled into a cylindrical shape is directed to the affected area A. . The cell sheet 1 pushed out from the tube 4 tries to return to its original substantially flat shape due to its elasticity. Therefore, by extruding in a state where the cut 1b is directed toward the affected area A, it quickly spreads to a form that covers the affected area A, so that it can be applied to the affected area A without adjusting the posture after release.

Next, a method for releasing the cell sheet 1 according to the second embodiment of the present invention will be described below with reference to FIGS.
In the present embodiment, as shown in FIG. 2, the cell sheet member 11 is configured by adhering a ring-shaped spacer 10 to the outer peripheral edge of the adhesion surface 1a of the cell sheet 1 formed in a substantially circular sheet shape. To do. The cell sheet 1 and the spacer 10 have a diameter dimension substantially equal to the inner diameter dimension of the tube 4 that can be inserted into the channel 3 provided in the insertion section 2 of the endoscope.

  The spacer 10 is made of, for example, a bioabsorbable material, and after being released in the vicinity of the affected part A, it is absorbed over time and disappears. The material of the spacer 10 is sufficient as long as it has biocompatibility, and may not have bioabsorbability. The spacer 10 remaining without being absorbed is left in the affected area as it is, or is discharged outside the body as a foreign object. In addition, when the spacer 10 is made of a bioabsorbable material, a medicine for treating the affected area A may be mixed.

  As shown in FIG. 3, the cell sheet member 11 configured as described above is inserted into the tube 4 so as to be stacked in the thickness direction. Since the spacer 10 is disposed on the adhesion surface 1a, the adhesion surface 1a is prevented from adhering to the adjacent cell sheet 1. Further, since the outer peripheral edge of the bonding surface 1 a is covered with the spacer 10, the bonding surface 1 a of the cell sheet 1 is also prevented from being bonded to the inner surface of the tube 4.

  As shown in FIG. 3, the cell sheet 1 releasing method according to the present embodiment presses the cell sheet 1 in the tube 4 by the pressing means 5 introduced from the rear of the tube 4 and pushes it out from the tip of the tube 4. It is. As the pressing means 5, for example, a device that presses and extrudes the cell sheet 1 with a liquid such as a wire or water is employed.

  Since the cell sheet 1 according to the present embodiment is a relatively small cell sheet 1 equivalent to the inner diameter of the tube 4 that can be inserted into the channel 3 of the insertion portion 2 of the endoscope, the cell sheet 1 is applied to an extremely small affected area A. Except for the case, it is necessary to apply a plurality of cell sheet members 11 to the affected area A as shown in FIG. As shown in FIG. 4, it is desirable to arrange the cell sheet member 11 so as to cover the entire affected area A. However, since the adhered cells grow and have a function of repairing the affected area A, it is shown in FIG. As described above, the cell sheet member 11 may be arranged so as to partially cover the affected area A.

Next, a method for releasing the cell sheet 1 according to the third embodiment of the present invention will be described below with reference to FIGS.
The release method according to this embodiment uses a cap 12 shown in FIG.

  As shown in FIG. 6, the cap 12 is formed in a substantially cylindrical shape, and includes a fitting portion 13 that can be fitted to the distal end of the insertion portion 2 of the endoscope on one end side in the longitudinal axis direction. . Further, the other end side of the cap 12 is provided with an adhesive portion 12a whose inner surface is subjected to a temperature responsive process. The adhesive portion 12a is subjected to a temperature responsive treatment to exhibit hydrophobicity at 32 ° C. or higher and hydrophilicity at a temperature lower than 32 ° C.

  Thereby, the cell sheet 1 can be kept in the adhesive state on the adhesive part 12a by maintaining at 32 ° C. or higher, and the cell sheet 1 of the adhesive part 12a is peeled off by switching to a lower temperature. Can be done. Moreover, the surface other than the adhesion part 11 is processed so as to have hydrophilicity. This prevents cells from adhering to the surface other than the adhesive portion 12a at any temperature.

In order to adhere the cell sheet 1 to such a cap 12, for example, as shown in FIG. 7, a cell suspension B in which the cells to be adhered are suspended is placed on one of the caps 12 whose longitudinal axis is substantially horizontal. The part is immersed, and the cap 12 is rotated around the longitudinal axis in this state, and the culture is rotated by maintaining predetermined culture conditions such as a temperature of 37 ° C., a humidity of 100%, and a CO ₂ concentration of 0.5%. As a result, cells adhere to and grow on the adhesion part 12a that has been subjected to the temperature-responsive treatment, and cells do not adhere to other surfaces, so that the cell sheet 1 is formed only on the adhesion part 12a. become.

  In this way, the cap 12 to which the cell sheet 1 is adhered is taken out from the cell suspension B, and the fitting portion 13 is fitted to the distal end of the insertion portion 2 of the endoscope as shown in FIGS. For example, the cutting line 1b is formed along the longitudinal axis. Thereby, the cap 12 to which the cell sheet 1 is adhered can be disposed in the vicinity of the affected part A by inserting the insertion part 2 of the endoscope orally or transanally into the body cavity.

  When the cap 12 is arranged in the vicinity of the affected part A, it is arranged around the outlet of the channel 3 by supplying cooling water having a temperature lower than 32 ° C. through the channel 3 provided in the insertion part 2. The cap 12 is cooled to change the property of the bonding portion 12a to hydrophilic. Thereby, the cell sheet 1 adhered to the adhesion part 12a is easily peeled off and supplied toward the affected part.

  In this case, according to the method for releasing the cell sheet 1 according to the present embodiment, the cell sheet 1 held by the adhesive portion 12a provided on the inner surface of the cap 12 is released, and therefore the cell sheet 1 is attached to the adhesive surface 1a. Is released in the form of a cylinder facing the outside. Therefore, it can be easily adhered to the affected part A arranged near the release position.

  In the present embodiment, the cap 12 is cooled by supplying cooling water through the channel 3 provided in the insertion portion 2 of the endoscope. As shown, a flow path 14 that passes through the inside of the wall surface of the cap 12 is provided, and an external water supply tube 15 that is led through the outside of the insertion portion 2 is connected to the flow path 14, thereby allowing the water supply tube 15 to pass through. The cooling water may be circulated in the flow path 14 of the cap 12 to cool the cap 12.

  Moreover, in the said embodiment, although it decided to provide the adhesion part 12a in the inner surface of the cap 12, instead of this, the cell sheet 1 was attached to the adhesion part 12a provided in the outer surface of the cap 12, as FIG. May be adhered. By doing in this way, the operation | work which forms the cutting line 1b in the cell sheet 1 can be made easy.

  In the present embodiment, the cell sheet 1 is formed in an adhesive state on the adhesive portion 12a provided on the cap 12 by rotating and culturing the cap 12 in the cell suspension B. Instead of this, the cell sheet 1 manufactured in another place may be bonded to the bonding portion 12a.

  Further, instead of adhering the cell sheet 1 to the outer surface of the cap 12, a temperature responsive process is performed on the outer peripheral surface of the insertion portion 2 itself of the endoscope to form an adhesion portion, and the cell sheet 1 is adhered to the adhesion portion. You may decide to make it.

Next, a method for releasing the cell sheet 1 according to the fourth embodiment of the present invention will be described below with reference to FIGS.
As shown in FIG. 12, the cell sheet 1 releasing method according to the present embodiment uses a member that has been subjected to a temperature-responsive treatment in the same manner as in the third embodiment. While the form is such that the cell sheet 1 is adhered to the cap 12 attached to the distal end of the insertion portion 2 of the endoscope, in the present embodiment, the insertion is performed in the same manner as in the first and second embodiments. A method of transporting and releasing to the vicinity of an affected area A in a state of being accommodated in a channel 3 of the section 2 is provided.

In the present embodiment, a flexible temperature-responsive sheet 20 in which the surface 20a is subjected to a temperature-responsive process or a temperature-responsive sheet 20 made of a temperature-responsive polymer is used.
And in order to accommodate in the channel 3 the composite sheet 21 which adhered the cell sheet 1 to the surface of such a temperature-responsive sheet 20, it rolls so that the composite sheet 21 may be wound up as shown in FIG. Thus, the outer diameter is made smaller than the inner diameter of the channel 3.

In this way, the cell sheet 1 having a significantly larger area can be accommodated in the channel 3 as compared with the case where the cell sheet 1 is rolled up into a single cylinder as in the first embodiment. Can do.
And the release method of the cell sheet 1 which concerns on this embodiment is after pushing the composite sheet 21 out of the channel 3 with the press means 5, such as a wire introduced from the back of the channel 3, similarly to 1st Embodiment. The cooling water introduced through the channel 3 is applied to the composite sheet 21 to cool to a temperature lower than 32 ° C., and the cell sheet 1 can be easily detached from the temperature-responsive sheet 20 and released to the vicinity of the affected area A. it can.

  In the present embodiment, the composite sheet 21 in which the cell sheet 1 is simply stacked on the temperature responsive sheet 20 composed of the temperature responsive polymer is illustrated, but instead of this, the shape memory alloy is placed inside the flexible sheet. You may employ | adopt the temperature responsive sheet 20 comprised by what embedded (not shown) or the shape memory polymer. By doing in this way, by giving a temperature change, the state spread flatly in FIG. 11 and the state wound in the cylindrical shape of FIG. 12 can be easily switched.

  Thereby, the work of inserting the composite sheet 21 into the channel 3 can be facilitated, and the deployment at the time of release can be performed smoothly. Further, when the cell sheet 1 is released, it can be spread as shown in FIG. 11, wound up as shown in FIG. 12 after the release, and collected again in the channel 3.

  Further, in the present embodiment, the composite sheet 21 is accommodated in the channel 3 to be transported and released in the vicinity of the affected part A. However, the composite sheet 21 is not accommodated in the channel 3 and the endoscope 21 You may decide to convey the inside of a body cavity in the state hold | gripped at the front-end | tip of the insertion part 2 with forceps etc. which are not shown in figure. By doing in this way, the process of extruding from the inside of the channel 3 becomes unnecessary, and the cell sheet 1 can be released to the vicinity of the affected area A simply by cooling.

  Further, in place of the flat temperature-responsive sheet 20, an expandable metal stent (not shown) or the like is provided inside the composite sheet 21 in which the cell sheet 1 is attached to the outer surface of the temperature-responsive sheet 20 formed in a cylindrical shape. It is good also as arrange | positioning the expansion means. By doing in this way, the composite sheet 21 comprised in the state which expanded the metal stent can be drawn near by shrinking | reducing a metal stent radially inward, and can reduce the outer diameter dimension. In this state, it can be accommodated in the channel 3 of the insertion portion 2. Moreover, after releasing from the channel 3 of the insertion part 2, the cell sheet 1 can be expanded by expanding the metal stent so that the composite sheet 21 that has been gathered is stretched. By cooling the temperature-responsive sheet 20 in this state, the cell sheet 1 can be easily peeled off and released to the vicinity of the affected part A.

  Similarly, a balloon (not shown) in which the cell sheet 1 is attached to the surface of a balloon whose surface has been subjected to a temperature responsive treatment may be employed. By attaching the cell sheet 1 in a state where the balloon is expanded and contracting the balloon, the cell sheet 1 can be easily accommodated in the channel 3 of the insertion portion 2. Then, after being released from the inside of the channel 3, the cell sheet 1 that has been gathered can be expanded so as to be stretched by inflating the balloon. In this state, by cooling the balloon, the cell sheet 1 can be easily peeled and released to the vicinity of the affected area A.

  Similarly, the temperature-responsive sheet 20 may be attached to the inside of an annular snare (not shown) made of wire, and the cell sheet 1 may be attached to the temperature-responsive sheet 20. By making the snare into a storage form, the composite sheet 21 can be easily configured to have a thickness that can be stored in the channel 3, and by projecting the snare out of the channel 3, the composite sheet can be made by the elasticity of the snare. 21 can be widened.

  Moreover, in the said 3rd and 4th embodiment, although the method of cooling the temperature-responsive member 20 which adhere | attached the cell sheet 1 was employ | adopted as a release method, it replaces with this and the adhesive surface of the cell sheet 1 is used. A protective sheet (not shown) such as alginic acid may be adhered to 1a, and the protective sheet may be peeled off in the vicinity of the affected area A. Moreover, although the temperature-responsive member 20 that switches between hydrophilicity and hydrophobicity depending on the temperature is used, instead of this, a member that switches between hydrophilicity and hydrophobicity by an electric field may be used.

It is a perspective view explaining the release method of the cell sheet which concerns on the 1st Embodiment of this invention, (a) The cell sheet of the accommodation state in a tube, (b) The cell sheet partially extruded from the tube, c) Each cell sheet released from the tube is shown. It is a perspective view explaining the cell sheet member used for the release method of the cell sheet which concerns on the 2nd Embodiment of this invention. It is a longitudinal cross-sectional view explaining the release method of the cell sheet | seat of FIG. It is a figure which shows an example of the cell sheet released to the affected part vicinity by the cell sheet release method of FIG. 3, and adhere | attached on the affected part. It is a figure which shows the other example of the cell sheet released to the affected part vicinity and adhere | attached on the affected part similarly to FIG. It is a perspective view which shows the cap used for the release method of the cell sheet which concerns on the 3rd Embodiment of this invention. It is explanatory drawing which shows the adhesion method of the cell sheet to the adhesion part of the cap of FIG. It is a perspective view which shows the state which attached the cap to which the cell sheet was adhere | attached with the adhesion | attachment method of FIG. 7 to the front-end | tip part of an endoscope. It is a longitudinal cross-sectional view which shows the state of FIG. It is a longitudinal cross-sectional view which shows the modification of FIG. It is a longitudinal cross-sectional view which shows the other modification of FIG. It is a perspective view explaining the composite sheet used for the release method of the cell sheet which concerns on the 4th Embodiment of this invention. It is a perspective view which shows the state which rounded the composite sheet | seat of FIG.

Explanation of symbols

A affected area 1 cell sheet 1a adhesive surface 1b cut 4 tube 5 wire (pressing means)
10 Spacer 11 Cell sheet member 20 Temperature responsive member

Claims (9)

  A cell sheet in which a cell sheet with a bonding surface facing inward in the radial direction is housed inside, and the cell sheet is pushed out of the tube by pressing means guided from the rear of the tube with the tip disposed in the vicinity of the affected part. Release method.   The cell sheet release method according to claim 1, wherein the cell sheet is rolled in a state of being cut toward a bonding site.   A cell sheet member in which a tubular spacer made of a biocompatible material having a predetermined thickness is attached to the outer peripheral portion of the adhesive surface of the cell sheet shaped into a circle is accommodated inside, and the tip of the tube is arranged in the vicinity of the affected part. A cell sheet releasing method in which a cell sheet member is pushed out of a tube by pressing means guided from the rear.   A cell sheet release method for cooling a temperature-responsive member in the vicinity of an affected area in a state in which a temperature-responsive member having temperature responsiveness that switches between hydrophilicity and hydrophobicity depending on temperature is adhered to an adhesive surface of the cell sheet.   The cell sheet release method according to claim 4, wherein the temperature-responsive member has a sheet shape.   The cell sheet release method according to claim 4 or 5, wherein the temperature-responsive member is formed of a deformable member.   The cell sheet release method according to claim 6, wherein the temperature-responsive member includes a shape memory actuator.   The cell sheet release method according to claim 6, wherein the temperature-responsive member is a metal stent.   The cell sheet release method according to claim 6, wherein the temperature-responsive member is a balloon.

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