JP2014079170A - Holding member for film-like tissue and preservation transport vessel using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a holding member for film-like tissue and a preservation transport vessel using the holding member, capable of preventing a film-like tissue from being damaged due to vibrations applied to the vessel during transport of the film-like tissue and also effectively preventing the film-like tissue from being damaged when the film-like tissue is later removed from within the vessel.SOLUTION: A holding member for film-like tissue according to the present invention is a tabular holding member 1 which is fixedly arranged within a vessel 50 for accommodating a film-like tissue 100 and holds the film-like tissue 100 within the vessel with a preservation liquid kept therein. The holding member 1, when so positioned as to be arranged within the vessel 50, provides a tissue placement space 4 recessed from peripheries toward a bottom part 51b side of the vessel 50, on at least a part of a surface 3 opposite to a back surface 2 facing the bottom part 51b side of the vessel 50, and also provides a plurality of liquid passing-through holes 5 penetrating in a thickness direction.

Description

  The present invention is, for example, a plate-like holding for holding the membranous tissue inside the container that is fixedly arranged inside a container that contains membranous tissue composed of cells derived from a living body and that contains a preservation solution. The present invention relates to a member and a storage and transportation container using the member, and in particular, proposes a technique capable of effectively preventing breakage of a fragile membranous tissue caused by vibration or the like applied to the container during transportation or the like. Is.

  In recent years, in the field of regenerative medicine that restores the function of organs or tissues lost due to illness or injury, skeletal myoblasts collected from the muscles of patients are cultured in cell culture centers, for example, and formed into sheets Then, to prepare a so-called skeletal myoblast sheet or other membranous tissue, and to store such membranous tissue in a container containing a preservation solution for use in transplantation to a patient, and The container containing the membranous tissue may be transported to a medical institution such as a hospital.

Here, the above-mentioned membranous tissue is extremely thin and extremely fragile, and when transported to a medical institution, the liquid level of the preservation solution rippls due to vibration input to the container, etc. As a result, the membranous tissue in the preservation solution may be damaged in the container.
In order to prevent such damage of the membranous tissue, Patent Document 1 states that “a membranous tissue storage and transport container used for storing or transporting membranous tissue composed of cells derived from a living body, A storage portion having a size capable of storing the membranous tissue in a state in which the size of the original shape is maintained, and a storage solution filled in the storage portion to such an extent that a gas layer is not formed in the storage portion. A membranous tissue storage and transport container is proposed, wherein the membranous tissue is stored in a floating state in the storage solution filled in the storage section.

  And, according to the storage transport container for membranous tissue described in Patent Document 1, “the interior of the container is filled with the storage liquid, and the membranous tissue is suspended in the storage liquid. Even if the container vibrates, the storage solution inside does not wave or flow, preventing vibrations from being transmitted to the membranous tissue and preventing the membranous tissue from being damaged. It can be done. "

JP 2012-130111 A

  By the way, after the membranous tissue is transported to a medical institution as described above, the membranous tissue is generally taken out from the inside of the storage transport container using, for example, a metal spatula and the like. It is transferred to another container such as a petri dish, and after laminating operation to make the membranous tissue multi-layered and washing the membranous tissue, the membranous tissue can be used for transplantation to a patient. When taking out from the inside of a preservation | save transport container and also when injecting / extracting a washing | cleaning liquid in a container, there existed a problem that there existed a possibility that a thin and thin film-like structure | tissue might be damaged.

  The present invention has been made in order to solve such problems of the prior art, and the object of the present invention is to input vibration to the container during transport of the membranous tissue. A membranous tissue holding member capable of effectively preventing subsequent damage to the membranous tissue during the removal of the membranous tissue from the inside of the container, while preventing the membranous tissue from being damaged, and to use the same It is to provide a storage transport container.

The membranous tissue holding member of the present invention is fixedly arranged inside a container containing a membranous tissue composed of cells derived from a living body, and holds the membranous tissue inside the container containing a preservation solution. Of, for example, a plate-like holding member, and at least part of the surface of the container facing the bottom side of the container and facing away from the back surface of the container, rather than the surrounding parts. For example, a plurality of liquid passage holes penetrating from the front surface to the back surface are provided and a tissue arrangement space having a size into which the entire membranous tissue enters is provided. It is a feature.
The term “fixed” as used herein means that when the holding member is arranged inside the container, for example, a part of the holding member abuts against the inner surface of the container, and thus the positional displacement of the holding member inside the container occurs. Means no.

  In the membranous tissue holding member of the present invention, it is preferable that the tissue arrangement space provided on the surface is formed with a curved surface that is recessed toward the bottom side of the container.

In the membranous tissue holding member of the present invention, the tissue placement space is positioned at the central portion of the surface, and the outer peripheral side portion extending around the outer peripheral side around the central portion is made flat. It is preferable.
In this case, the tissue placement space is formed in the bottom surface region located closest to the bottom side of the container and around the bottom surface region, and a gradient with respect to a plane parallel to the flat surface of the outer peripheral side portion is formed in the bottom surface region. It is preferable that the liquid passage hole is provided only in the bottom surface region and the outer peripheral side portion.

  Further, the membranous tissue storage and transport container of the present invention has the above-mentioned membranous tissue holding member disposed inside the container, and has a container body having an opening, and is attachable to and detachable from the container body. And a lid member that seals the opening, and the membranous tissue is stored inside a container filled with a preservative solution to store or transport the membranous tissue. The holding member is arranged in such a direction that the surface provided with the tissue arrangement space faces the inner surface of the lid member, and the back surface opposite to the surface faces the bottom of the container body. In addition, at least a part of the peripheral portion of the holding member is brought into contact with the container body or the lid member, and the holding member is fixedly arranged inside the container.

According to the membranous tissue holding member of the present invention, at least part of the surface of the container facing the bottom side of the container and facing away from the back surface facing the bottom side of the container is more than the surrounding part. By providing a tissue placement space that is recessed toward the bottom side of the container, when fixedly placed inside the container, the tissue placement space that is recessed on the container bottom side is the membrane-like tissue disposed there, for example, Since it functions to regulate the movement of the inside of the container filled with the preservation solution, it is possible to effectively prevent damage during transportation of the membranous tissue.
Here, by providing a plurality of liquid passage holes penetrating from the front surface to the back surface, the preservation liquid is injected into the container, removed from the container, and transport of the membrane tissue. In this case, the preservation solution can smoothly flow between the inner regions existing on both sides of the holding member in the container.

When removing the membranous tissue from the inside of the container, after removing the preservation solution inside the container, the holding member is taken out from the inside of the container together with the membranous tissue arranged in the tissue arrangement space. Then, when the holding member is turned over so that the tissue arrangement space of the holding member faces downward, the wet membrane structure is adsorbed and held in the tissue arrangement space based on the capillary phenomenon in the liquid passage hole provided in the holding member. The Then, by pressing the back surface of the holding member in the inverted state, the membranous tissue is placed at the intended position on the transplant surface of the patient at the time of transplant without using a metal spatula or the like. Or a laminating operation can be performed when the membranous structure is multilayered.
Therefore, according to the membranous tissue holding member of the present invention, it is possible to effectively prevent the membranous tissue from being damaged when the membranous tissue is taken out from the inside of the container after transportation, for example.

  Moreover, according to the preservation | save transport container of the membranous structure | tissue of this invention, damage to a membranous structure | tissue can be effectively prevented similarly to the place mentioned above by the holding member arrange | positioned inside the container.

It is a perspective view which shows one Embodiment of the holding member of the membranous structure | tissue of this invention. It is sectional drawing in alignment with the depth direction of a container which shows the holding member of FIG. 1 with the preservation | save transport container which has arrange | positioned it inside. It is a perspective view which shows each process which takes out a membranous structure | tissue from the inside of a container using the holding member of FIG. It is sectional drawing in alignment with the depth direction of a container which shows other embodiment of the holding member of the membranous structure | tissue of this invention with the storage transport container which has arrange | positioned it inside.

Embodiments of the present invention will be described below with reference to the drawings.
In the example illustrated in FIG. 1, reference numeral 1 in FIG. 1 is fixedly arranged in a container to be described later that stores a membrane-like tissue composed of cells derived from a living body, and manages the maintenance of the membrane-like tissue inside the container. FIG. 2 shows a substantially disk-shaped holding member having a circular outer contour shape.

  Note that the membranous tissue held by the holding member 1 is a thin film having a certain thickness, and includes organs and tissues such as the heart, cornea, retina, blood vessels, nerves, epidermis, dermis, cartilage, and teeth. It is used for the purpose of regeneration, treatment, healing promotion for diseases, illnesses and defects in some or all organs, or multiple organs, or the irritation, sensitization, toxicity, drug It is a structure derived from a living body used for examining effects, reaction to tissues, etc., and as this membranous tissue, for example, skin tissue, mucosal epithelial tissue, corneal epithelial tissue, cultured skin, cultured dermis, cultured epidermis, Cultured epithelial tissue, cultured corneal tissue, cartilage tissue, retinal tissue, neurofilament, artificial blood vessel, myoblast tissue, sheet-like cell culture made from living body structures, especially sheets composed of skeletal myoblasts Cell culture It can be mentioned. The membranous tissue can be composed only of cells and cell secretions, and can further contain substances that are not derived from living bodies such as a support.

Here, as shown in a cross-sectional view in FIG. 2, the holding member 1 fixedly disposed inside the storage transport container 50 is disposed at the bottom of the storage transport container 50 in a state of being disposed inside the storage transport container 50. Indented toward at least a part of the surface 3 facing the opposite side (the lower side in FIG. 2) and the opposite side (the upper side in FIG. 2) toward the bottom side of the storage transport container 50 rather than the surrounding parts The tissue arrangement space 4 is provided and in which the above-described membranous tissue 100 is arranged.
Further, here, the holding member 1 is provided with a plurality of liquid passage holes 5 penetrating in the thickness direction of the holding member 1.

  When such a holding member 1 is arranged inside the container, for example, the entire inside of the storage transport container 50 constituted by the container main body 51 having the opening 51a and the lid member 52 is completely filled with the storage liquid. In the state, when the membranous tissue 100 is transported, the membranous tissue 100 arranged in the tissue arrangement space 4 is in the tissue arrangement space 4 even when the storage transport container 50 is vibrated along with the transportation. Since the movement of the membranous tissue 100 inside the container is restricted by the contact with the surface region forming the film, the membranous tissue 100 floating in the preservation solution collides with the inner surface of the container at the time of transportation. It is possible to effectively prevent the membranous tissue 100 from being damaged. For example, a liquid medium, physiological saline, isotonic solution, buffer solution, Hank's balanced salt solution, or the like can be used as the preservation solution to fill the inside of the container.

  1 and 2, in order to facilitate the molding of the holding member 1 which can be formed of, for example, a resin material, the thickness of the holding member 1 is constant throughout the holding member 1. The shape of the back surface 2 is a convex shape that protrudes toward the bottom of the container, following the shape of the front surface 3 in the region where the tissue placement space 4 is formed, so that the holding member 1 has a dish-like shape as a whole. As long as the tissue arrangement space 4 that is recessed toward the bottom of the container is formed on the front surface 3 side of the holding member 1, the back surface shape of the holding member 1 is not limited to the illustrated form.

  Here, from the viewpoint of effectively exerting the function of restricting the movement of the membranous tissue 100 by the tissue arrangement space 4 while more reliably preventing damage to the membranous tissue 100 in contact with the tissue arrangement space 4. The tissue placement space 4 is preferably a curved surface formed by, for example, an arc having one or a plurality of curvature radii in a cross section along the thickness direction of the holding member 1 shown in FIG.

Here, as shown in FIGS. 1 and 2, the tissue arrangement space 4 can be positioned, for example, at the center portion of the surface 3 of the holding member 1 having a disk shape. In this case, the tissue arrangement space 4 An outer peripheral side portion 6 extending from the central portion to the outer peripheral side along the radial direction (left and right direction in FIG. 2) of the holding member 1 and surrounding the periphery of the central portion is formed, for example, by the holding member. It can be made into the flat shape parallel to the plane in alignment with 1 radial direction.
And here, the tissue placement space 4 is located closest to the bottom of the container among the regions of the surface 3, for example, a bottom region 4a slightly smaller than the size of the membranous tissue 100 held by the holding member 1, A side surface region 4b that is formed around the bottom surface region 4a and is parallel to the flat surface of the outer peripheral side portion 6 and has a relatively steep gradient with respect to the plane along the radial direction as compared with the bottom surface region 4a. It is preferable.
Thereby, as shown in FIG. 2, the membranous tissue 100 can be arranged on the bottom surface region 4a so as to be surrounded by the side surface region 4b, so that more stable holding of the membranous tissue 100 can be realized. it can.

Further, when the tissue arrangement space 4 is configured by the bottom surface region 4a and the side surface region 4b as described above, it is preferable that the liquid passage hole 5 described above is provided only in the bottom surface region 4a and the outer peripheral side portion 6.
This ensures that the membranous tissue 100 may be damaged by the water hammer of the storage solution flowing into the tissue placement space 4 from the fluid passage hole 5 provided in the side region 4b when the storage solution is injected into the storage transport container 50. Because it can be removed.

Here, the tissue placement space 4 has such a size that the entire membranous tissue 100 having a circular planar outline shape with a diameter of about 5 mm to 100 mm enters, for example, and the opening diameter of the tissue placement space 4 R can be 1 to 5 times the diameter of such membranous tissue 100.
Further, the liquid passage hole 5 can have a size that does not allow the membranous tissue 100 to enter, and the diameter of the liquid passage hole 5 is 0.01 to 0.5 times the diameter of the membranous tissue 100. can do.

By the way, the storage and transport container 50 illustrated in FIG. 2 has a cylindrical container main body having one end side (lower side in FIG. 2) sealed with a bottom 51b and an opening 51a on the other end side (upper side in FIG. 2). 51 and a lid member 52 that is detachably attached to one end portion of the container body 51 and is attached to one end portion of the container body 51 to seal the opening 51a.
And in this preservation | save transport container 50, in order to ensure the liquid-tightness in the attachment location to the container main body 51 of the cover member 52, between the cover member 52 and the container main body 51 in the opening part 51a of the container main body 51, An annular seal member 53 such as an O-ring is sandwiched and provided, and one or more clip members 54 are disposed to sandwich and fix the lid member 52 and the container body 51 while the annular seal member 53 is sandwiched.

  Here, the holding member 1 having an outer diameter slightly smaller than the inner diameter of the container main body 2 causes the peripheral portion of the holding member 1 to abut the inner surface of the container main body 51 of the storage transport container 50 over the entire circumference. In this state, it is fixedly placed inside the container. Thereby, even if it is a case where a vibration is added to the preservation | save transport container 50, the movement of the holding member 1 inside a container will be controlled.

As described above, when the holding member 1 is fixedly disposed in contact with the inner side surface of the container main body 51, if the holding member 1 is in contact with the container main body 51 in at least one place, The movement of the holding member 1 can be effectively restricted.
In FIG. 2, the holding member 1 is fixedly arranged on the container body 51 side of the storage transport container 50, but although not shown, it can also be fixed on the lid member 52 side of the storage transport container 50. It is.

Further, here, on the side wall of the container main body 2, the tip of the storage liquid injection / removal instrument (not shown) such as a syringe, a connector, etc., at a position closer to the bottom than the position where the holding member 1 contacts the inner surface of the container main body 2. Is inserted, and a liquid passage part 55 with a stopper or a valve, for example, that contributes to the injection of the preservation solution into the container and the removal from the container is provided.
Accordingly, in the storage and transport container 50, the container interior is partitioned into two internal regions, the lid member 52 side and the container bottom 51b side, by the holding member 1 disposed inside the container. In the state where the lid member 52 is attached to the container, the storage liquid is injected from the liquid passage portion 55, so that the storage liquid gradually stored from the container bottom 51 b side is stored in the liquid passage hole 5 provided in the holding member 1. From the inner region on the container bottom 51b side to the inner region on the lid member 52 side, the inside of the container can be filled with the storage solution.

  When the membranous tissue 100 accommodated and placed together with the preservation solution is taken out from the preservation / transport container 50 in which the holding member 1 as described above is arranged, the inside of the container is used when the membranous tissue 100 is used for transplantation. For example, after the storage solution filled in is removed to the outside of the container by the liquid passage portion 55 described above, and the lid member 52 is removed from the container main body 51, as shown in FIG. Is placed in the tissue placement space 4 and the holding member 1 is taken out of the container together with the membranous tissue 100 using, for example, tweezers.

  In addition, you may perform a washing | cleaning process as needed. In this case, the holding member 1 in which the membranous tissue 100 is arranged in the tissue arrangement space 4 is placed in another container such as a petri dish, and the membranous tissue 100 is washed by adding a cleaning liquid to the container. Since the holding member 1 is provided with a plurality of liquid passage holes 5, the cleaning liquid accumulates in the container and the holding member 1 through the liquid passage holes 5. Since the cleaning liquid drops through the liquid passage hole 5 by pulling up the holding member 1 from the cleaning liquid filled in the container, the cleaning can be completed while leaving only the membranous tissue 100 in the holding member 1.

Next, as shown in FIG. 3B, the holding member 1 taken out from the inside of the container is turned over so that the tissue placement space 4 faces the transplant surface as shown in FIG.
At this time, the membrane-like tissue 100 in the wet state arranged in the tissue arrangement space 4 does not fall on the transplantation surface due to capillary action in the plurality of liquid passage holes 5 provided in the tissue arrangement space 4. Then, it is adsorbed and held in the tissue arrangement space 4. In addition, as described above, there is a case where a laminating operation for laminating a membranous tissue is performed before transplantation.

Then, the tissue placement space 4 is pressed from the back surface 2 side of the holding member 1 using a pusher 150 or the like, and the holding member 1 is elastically deformed, whereby the membranous tissue 100 is transferred to the tissue placement space. The adsorbed and held state is released, and the membranous tissue 100 can be placed at the intended position on the transplant surface.
In order to realize such detachment of the membranous tissue 100 from the tissue placement space 4, the holding member 1 does not deform in a state where no external force is applied, but is flexible enough to be elastically deformed by the action of the external force. In addition, the holding member 1 is formed of a material that does not have an inherent fixing force to the membranous tissue 100, and the thickness of the holding member 1 is measured along a normal line standing on the surface 3, for example, 1 mm to 10 mm. It is preferable. Also, for example, the hardness of the holding member 1 can be set to 5 to 100 according to JIS K6253.

The holding member 11 according to another embodiment shown in FIG. 4 has a constant curvature, for example, in the cross section shown in the figure, over the entire surface 13 toward the container bottom 51b side rather than the peripheral part in contact with the container main body 51. Except for providing a tissue placement space 14 that is recessed by a curved surface having a radius, it has substantially the same configuration as the embodiment shown in FIGS.
Even in the holding member 11 provided with such a tissue arrangement space 14, for example, when the peripheral portion of the membrane tissue 100 contacts the curved surface 13, the membrane tissue 100 inside the container is brought into contact. Since the movement is limited, it is possible to effectively prevent damage to the membranous tissue 100 during transportation. In addition, when the membranous tissue 100 is taken out from the inside of the container, the membranous tissue 100 is attached together with the holding member 11. By taking out, damage to the membranous tissue 100 at that time can be effectively prevented.

  In addition, in the place mentioned above, as a material of a holding member, for example, natural rubber, isoprene rubber, butadiene rubber, styrene-butadiene rubber, nitrile rubber, chloroprene rubber, butyl rubber, acrylic rubber, ethylene-propylene rubber, hydrin rubber, urethane rubber , Various rubber materials such as silicone rubber, fluoro rubber, styrene, polyolefin, polyvinyl chloride, polyurethane, polyester, polyamide, polybutadiene, trans polyisoprene, fluoro rubber, chlorinated polyethylene Various thermoplastic elastomers such as these can be mentioned, and one or more of these can be used in combination. In addition, an appropriate surface treatment can be applied to make the holding member less slippery or slippery as necessary. A sterilizable material such as an autoclave, EOG, and γ rays is preferable.

  Examples of the material forming the container body and the lid member include polyethylene, polypropylene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer (EVA), polyvinyl chloride, polyvinylidene chloride, polystyrene, polyamide. , Polyimide, polyamideimide, polycarbonate, poly- (4-methylpentene-1), ionomer, acrylic resin, polymethyl methacrylate, acrylonitrile-butadiene-styrene copolymer (ABS resin), acrylonitrile-styrene copolymer (AS Resin), butadiene-styrene copolymer, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polycyclohexane terephthalate (PCT), polyether, polyether ketone (PEK), Reether ether ketone (PEEK), polyether imide, polyacetal (POM), polyphenylene oxide, modified polyphenylene oxide, polysulfone, polyether sulfone, polyphenylene sulfide, polyarylate, aromatic polyester (liquid crystal polymer), polytetrafluoroethylene, polyfluoride Examples thereof include various resin materials such as vinylidene fluoride and other fluorine-based resins, blends containing at least one of these, and polymer alloys. In addition, it is also possible to configure with various glass materials, ceramic materials, and metal materials.

  The elastic material forming the annular seal member includes, for example, natural rubber, isoprene rubber, butadiene rubber, styrene-butadiene rubber, nitrile rubber, chloroprene rubber, butyl rubber, acrylic rubber, ethylene-propylene rubber, hydrin rubber, urethane. Various rubber materials such as rubber, silicone rubber, fluoro rubber, styrene, polyolefin, polyvinyl chloride, polyurethane, polyester, polyamide, polybutadiene, trans polyisoprene, fluoro rubber, chlorinated polyethylene Various thermoplastic elastomers, such as a type | system | group, are mentioned, Among these, 1 type (s) or 2 or more types can be mixed and used.

DESCRIPTION OF SYMBOLS 1,11 Membrane structure | tissue holding member 2,12 Back surface 3,13 Surface 4,14 Tissue arrangement space 4a Bottom surface area 4b Side surface area 5,15 Liquid passage hole 6 Peripheral side part 50 Membrane tissue storage transport container 51 Container body 51a opening 51b bottom 52 lid member 53 annular seal member 54 clip member 55 liquid passage part 100 membranous tissue 150 pusher R opening diameter of tissue arrangement space

Claims (5)

  A holding member for holding the membranous tissue inside the container, which is fixedly arranged inside a container for accommodating membranous tissue composed of cells derived from a living body and containing a preservation solution, And at least a part of the surface facing away from the back surface facing the bottom side of the container with a disposition posture to provide a tissue placement space that is recessed toward the bottom side of the container rather than surrounding parts A membranous tissue holding member comprising a plurality of liquid passage holes penetrating from the front surface to the back surface.   The membranous tissue holding member according to claim 1, wherein the tissue arrangement space provided on the surface is formed by a curved surface that is recessed toward the bottom side of the container.   2. The film-like shape according to claim 1, wherein the tissue arrangement space is positioned at a central portion of the surface, and an outer peripheral side portion extending around the outer peripheral side around the central portion is flattened. Tissue retention member.   The tissue placement space is formed relative to a bottom surface region that is located closest to the bottom side of the container and a plane parallel to the flat surface of the outer peripheral side portion relative to the bottom surface region. 4. The membranous tissue holding member according to claim 3, wherein the liquid passage hole is provided only in the bottom surface region and the outer peripheral side portion. The holding member for a membranous tissue according to claim 1 is disposed inside a container, and a container main body having an opening, and a lid member that is detachable from the container main body and is attached to the container main body to seal the opening. A membranous tissue storage container for storing or transporting the membranous tissue, storing the membranous tissue inside a container filled with a preservation solution,
The holding member is arranged in such a direction that the surface provided with the tissue arrangement space faces the inner surface of the lid member and the back surface opposite to the surface faces the bottom of the container body. At the same time, at least a part of the peripheral portion of the holding member is brought into contact with the container main body or the lid member, and the holding member is fixedly arranged inside the container.

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