JPWO2017158791A1 - Cell chamber for artificial organs - Google Patents

Abstract

It is an object to produce a chamber capable of predicting the production amount of substances such as hormones produced by stem cells.
For artificial organs, including a substrate, a through hole penetrating the substrate, and a recess formed on the substrate, wherein the through hole is sized to allow a blood vessel to be inserted, and the recess is sized to insert and hold a stem cell With this cell chamber, the production amount of substances such as hormones produced by stem cells can be predicted.

Description

  The present invention relates to a cell chamber for an artificial organ, and more particularly to a cell chamber that can be used as an artificial organ by inserting and holding a differentiated stem cell and placing it in a living body.

  When the function of tissues constituting the living body such as organs such as the heart, lungs, liver, kidneys, and pancreas, bones, and eyes is impaired, various diseases are caused. When the disease of the living tissue is relatively mild, the lesioned part can be cured by medication or surgery. However, when the function of the living tissue is remarkably lowered and healing is difficult, an artificial organ is used to substitute the function of the living tissue.

  Artificial organs are known as artificial organs made of mechanical elements such as ceramic artificial bones and implants, pacemakers, and artificial organs made by tissue engineering using living cells. Examples of the latter artificial organ include, for example, a diffusion chamber type in which pancreatic endocrine cells are encapsulated with a polymer membrane in pancreatic islets and / or pancreatic islet cells that are three-dimensionally cultured, and can be transplanted subcutaneously or in the abdomen of the patient. Artificial organs are known (see Patent Document 1). In addition, a pancreatic cell that can replace the original pancreas lost in a container V formed by adhering an immune isolation membrane made of polycarbonate to both opening end faces of the silicone rubber ring 2 and a cell culture bed 5 that maintains its function are provided. There is also known an artificial organ chamber that is sealed and filled with sponge chitin as a carrier for pancreatic cells in a container V (see Patent Document 2).

Japanese Patent Publication No. 7-28730 JP 2003-190259 A

  As described above, it is known to place a chamber containing cells in a living body. However, the inventions described in Patent Documents 1 and 2 are merely putting the cultured cells into the chamber. In order to actually use the artificial organ as an artificial organ, it is necessary to predict how much the artificial organ will produce the desired substance by placing the artificial organ in the living body. The described invention has a problem that the production volume cannot be predicted.

  Recently, research using stem cells such as ES cells and iPS cells has been actively conducted. However, the artificial organs described in Patent Documents 1 and 2 use cultured cells different from stem cells. Therefore, there is a problem that the chambers described in Patent Documents 1 and 2 cannot be used as they are for stem cells.

  The present invention has been made in order to solve the above-mentioned conventional problems, and as a result of extensive research, a recess having a size capable of inserting and holding stem cells is formed on the substrate of the cell chamber. Since the number of stem cells that can be inserted and held in one cell chamber is known, the production amount of substances such as hormones produced by the stem cells can be predicted, and the present invention has been completed.

  That is, an object of the present invention is to provide a cell chamber for an artificial organ.

  The present invention relates to a cell chamber for an artificial organ shown below.

(1) including a substrate, a through-hole penetrating the substrate, and a recess formed on the substrate;
A cell chamber for an artificial organ, wherein the through hole is sized to allow insertion of a blood vessel, and the recess is sized to insert and hold a stem cell.
(2) The cell chamber for an artificial organ according to (1) above, wherein the opening of the concave portion has a substantially circular shape with a diameter of 1 mm to 3 mm or a polygon with a diagonal line of 1 mm to 3.5 mm.
(3) The cell chamber for artificial organs according to (1) or (2) above, wherein the bottom of the concave portion has a continuous curved shape.
(4) The substrate includes a pedestal portion and a stem cell storage portion formed on one surface of the pedestal portion, and the through hole and the recess are formed in the stem cell storage portion. The cell chamber for an artificial organ according to any one of (3).
(5) The cell chamber for artificial organs according to (4) above, which includes a cover member that covers the stem cell storage unit.
(6) The stem cell storage portion includes a wall surface extending upward from the pedestal portion, and a stem cell storage surface in which the through hole and the recess are formed, and the stem cell storage surface is connected to a top portion of the wall surface. The artificial organ cell chamber according to (4) or (5) above, wherein a space is formed between the stem cell storage surface and the top of the wall surface by being positioned on the pedestal side.
(7) The artificial organ according to any one of the above (4) to (6), wherein an insertion hole is formed in the pedestal for insertion of a means for fixing the cell chamber to the body tissue. Cell chamber.

  The cell chamber for an artificial organ of the present invention is provided with a recess having a size capable of inserting and holding a stem cell. Therefore, the production amount of hormones and the like per cell chamber can be predicted from the number of recesses into which stem cells are inserted and held.

FIG. 1A is a perspective view illustrating an outline of a cell chamber 1 for an artificial organ according to the present invention, and FIG. 1B is a top view of the chamber 1. FIG. 2 shows an example in which the recesses 4 of the chamber 1 are arranged in a closely packed structure. FIG. 3 is a cross-sectional view for explaining another embodiment of the chamber 1 of the present invention.

  The cell chamber for artificial organs of the present invention will be described in detail below.

  FIG. 1A is a perspective view illustrating the outline of a cell chamber 1 for artificial organs of the present invention (hereinafter sometimes referred to as “chamber”), and FIG. It is a top view. The chamber 1 of the present invention includes at least a substrate 2, a through hole 3 penetrating the substrate 2, and a recess 4 formed on the substrate 2.

  In the embodiment shown in FIGS. 1A and 1B, the substrate 2 includes a pedestal portion 21 and a stem cell storage portion 22 formed on one surface of the pedestal portion 21. A shaped substrate may be used. When the chamber 1 includes the pedestal portion 21 and the stem cell storage portion 22, the pedestal portion 21 has a means for fixing to the body tissue when the chamber 1 is placed in the living body, for example, an insertion hole 23 for inserting a thread or the like. May be formed. The insertion hole 23 is not indispensable. When fixing to the living tissue, the pedestal 21 (the substrate 2 when the pedestal 21 is not provided) may be pierced and penetrated with a needle.

  The stem cell storage portion 22 is formed in a convex shape on one surface of the pedestal portion 21 and has a substantially trapezoidal cross section including a wall surface 221 and a stem cell storage surface 222 extending upward from the pedestal portion 21. . When forming the stem cell storage part 22, the through hole 3 and the recess 4 are preferably formed in the cell storage part 22.

  The substrate 2 is not particularly limited as long as it is a material that hardly causes a rejection reaction when placed in a living body, and examples thereof include silicon and polypropylene. The substrate 2 may be formed by forming a mold and performing injection molding, press molding, cutting, or the like. In addition, since the chamber 1 is used while being placed in a living body, it is desirable that the living tissue with which the chamber 1 abuts is not damaged. Therefore, it is desirable that the periphery of the substrate 2 (the pedestal portion 21 and the stem cell storage portion 22) has a smooth shape with no corners. Further, it is desirable that the substrate 2 is formed so as not to have a corner such as a circle or an ellipse.

  The through-hole 3 is a hole for acting on a stem cell inserted into the recess 4 when a blood vessel grows from a living tissue when the chamber 1 is placed in the living body. Therefore, the size of the through hole 3 is not particularly limited as long as it is a size capable of forming a blood vessel. Further, the position and the number of the through holes 3 are not particularly limited. However, if the number of the through holes 3 is too small with respect to the number of the recessed parts 4 to be provided, there is a possibility that the recessed parts 4 that cannot reach the blood vessels grown from the living tissue may come out. Substances such as hormones produced by stem cells may not be carried into the body. Therefore, the through holes 3 may be arranged in a distributed manner according to the number and arrangement of the recesses 4.

  The recess 4 is not particularly limited as long as stem cells can be inserted / held. In addition, since the artificial organ using the chamber of the present invention is placed in the living body, it becomes a foreign object for the living body. Accordingly, the number of substances produced by one artificial organ is increased as much as possible, that is, if the production amount of the substance is the same, the smaller the artificial organ, the better. For example, the concave portion 4 may be formed in a closely packed structure. FIG. 2 shows an example in which the recesses 4 are arranged in a finely packed structure. The through holes 3 may be formed between the recesses 4 at an appropriate interval so that blood vessels grown from the living tissue reach the recesses 4.

  The stem cells inserted and held in the recesses 4 can be either ES cells or iPS cells. ES cells and iPS cells may be cells cultured and differentiated by known methods. Further, the same type of stem cells may be inserted into one chamber 1 or different types of stem cells may be inserted.

  In order to obtain desired characteristics as an artificial organ, it is preferable to use cells cultured until stem cells are differentiated. The size of the differentiated stem cells is approximately 1 to 3 mm. Therefore, it is desirable that the shape of the opening 41 of the recess 4 is a size that allows substantially spherical stem cells having a diameter of 1 mm to 3 mm to pass through. For example, a substantially circular shape having a diameter of 1 mm to 3 mm, preferably 2 mm to 3 mm is preferable. Can be mentioned. Further, it may be a polygon such as a hexagon, a heptagon, or an octagon instead of a substantially circular shape. In the case of a polygon, the size of the opening 41 may be such that the length of the diagonal line passing through the center is 1 mm to 3.5 mm, preferably about 2.5 mm to 3.5 mm.

  Moreover, it is preferable that the bottom part 42 of the recessed part 4 is made into the continuous curved surface. Stem cells, especially iPS cells, can be transformed into other cells when placed on a flat surface. Therefore, it is preferable that the bottom 42 of the concave portion 4 has a continuous curved surface shape because the stem cell does not include a flat surface portion, so that the stem cells can easily maintain a spherical state. Among continuous curved shapes, a substantially hemispherical shape is more preferable. Moreover, you may water-repellently process the inner surface of the recessed part 4 as needed. The water repellent treatment is not particularly limited as long as it is a known method, and for example, a plasma apparatus or the like may be used. By subjecting the inner surface of the recess 4 to water repellency, the stem cells inserted into the recess 4 can be made more spherical.

  When the chamber 1 is used as an artificial organ, if the stem cell is placed in the living body with the stem cell inserted and held in the recess 4, the stem cell may flow out into the living body. If ES cells flow into the body, they may cause rejection, and if iPS cells flow into the body, they may become cancerous. Therefore, it is preferable to attach a semipermeable membrane that does not pass through the stem cells but can pass through the substance such as the produced hormone or can enter the capillaries, at least in the upper part of the recess 4 containing the stem cells in the chamber 1. In addition, when attaching the cover member mentioned later to the chamber 1, you may attach a semipermeable membrane to the lower side of the base part 21. FIG.

  The semipermeable membrane is not particularly limited as long as it satisfies the above characteristics. When the chamber 1 to which the semipermeable membrane is attached is placed in the living body, capillaries grow from the surrounding living tissue, and the capillaries can pass through the semipermeable membrane and be integrated with the stem cells to be organized. Even if the capillary does not pass through the semipermeable membrane, it can take up substances such as hormones that have passed through the semipermeable membrane if it grows to the vicinity of the semipermeable membrane.

  When producing an artificial organ, it is preferable to fill the recess 4 with an artificial cerebrospinal fluid instead of a stem cell culture solution. Moreover, although the chamber 1 may be used independently, after inserting a stem cell in the recessed part 4, you may laminate | stack two or more.

  FIG. 3 is a cross-sectional view for explaining another embodiment of the chamber 1 of the present invention, and a cover member 5 is attached to the chamber 1 of the embodiment shown in FIG. Artificial organs can be placed in various places, such as the cap aponeurosis and the abdominal cavity under the scalp, but depending on the place of placement, it may take some time for the capillaries to grow and interact with the stem cells. It may take. If the artificial cerebrospinal fluid filled in the recesses 4 disappears before the capillaries grow and interact with each other, the stem cells may die. The chamber 1 of the embodiment shown in FIG. 3 can replenish artificial cerebrospinal fluid between the substrate 2 and the cover member 5 by providing a cover member 5 on the substrate 2 and inserting a needle of a syringe from outside the body. . Therefore, even when the artificial organ is placed in a place where the capillary blood vessel is difficult to grow, the stem cell can be kept alive until the function is started as the artificial organ.

  The cover member 5 may be manufactured using polypropylene, silicon, or the like, similar to the substrate 2. In the embodiment shown in FIG. 3, the cover member 5 is engaged with the groove portion 23 formed near the boundary between the pedestal portion 21 and the stem cell storage portion 22 and the end portion 51 of the cover member 5. There is no particular limitation as long as it can be mounted on. Moreover, it is preferable that the cover member 5 has a smooth shape with no corners so as not to damage surrounding biological tissues when placed in the living body.

  When the artificial organ is placed in the living body, in order to inject the artificial cerebrospinal fluid with a needle, it is necessary to grasp the position of the artificial organ from outside the living body. Therefore, the convex portion 52 may be formed on a part of the cover member 5. By touching with a hand from above the skin and confirming the convex portion, the position to be injected with the needle can be grasped.

  If the cover member 5 is formed of a flexible material such as silicon, the injected artificial cerebrospinal fluid is filled between the cover member 5 and the stem cell storage portion 22, so that each concave portion 4 is interposed via the semipermeable membrane. Artificial cerebrospinal fluid can be supplied. If necessary, a space may be positively provided between the stem cell storage unit 22 and the cover member 5 so that more artificial cerebrospinal fluid can be injected. Specifically, as shown in FIG. 1 (A), the stem cell storage surface 222 provided with the through hole 3 and the recess 4 is not formed from the top of the wall surface 221 extending upward from the pedestal 21, but the pedestal is formed from the top. The stem cell storage surface 22 may be formed so as to provide the step 223 in the direction of the portion 21 and connect the end 224 of the step 223 on the side of the pedestal 21. By providing the step 222, the stem cell storage surface 222 is positioned closer to the pedestal 21 than the surface connecting the top of the wall surface 221, so that a space is formed between the stem cell storage surface 222 and the top of the wall surface 221, and more Artificial cerebrospinal fluid can be injected.

  When an artificial organ is produced using iPS cells, iPS cells may become cancerous. Since the artificial organ is provided with a semipermeable membrane, cancerous iPS cells do not enter the living body, but for safety reasons, the solution in the artificial organ is sampled every predetermined period to obtain iPS cells. It is preferable to examine the presence or absence of canceration. Canceration may be examined by a known method such as measuring a cancer marker protein or gene contained in a sampled solution. A cancerous artificial organ may be removed from the living body by surgery.

  The solution may be sampled by piercing a needle from outside the living body as in the case of artificial cerebrospinal fluid injection. When a predetermined period elapses after the artificial organ is placed in the living body, capillaries and the like pass through the through holes 3 and grow around the recesses 4 and in the recesses 4. When sampling a solution, damage to the grown capillaries with a needle may cause bleeding and the blood may irritate surrounding iPS cells. Therefore, it is preferable that there is no iPS cell at the place where the needle is inserted. For example, the iPS cell may be left empty without being inserted into the concave portion 4 immediately below the convex portion 52. In addition, if a semipermeable membrane is attached to the entire surface of the stem cell storage surface 222, the semipermeable membrane may be damaged each time a needle is punctured, and fragments or the like may be generated. For this reason, the semipermeable membrane may be shaped so as not to cover the recess 4 where no iPS cells are inserted.

When the cell chamber for artificial organs of the present invention is used, the production amount of substances such as hormones per artificial organ can be predicted. Therefore, it is useful for surgery in the medical device industry and medical institutions that produce artificial organs.

Claims (7)

Including a substrate, a through-hole penetrating the substrate, a recess formed on the substrate,
A cell chamber for an artificial organ, wherein the through hole is sized to allow insertion of a blood vessel, and the recess is sized to insert and hold a stem cell.   The cell chamber for an artificial organ according to claim 1, wherein the opening of the concave portion has a substantially circular shape with a diameter of 1 mm to 3 mm or a polygon with a diagonal line of 1 mm to 3.5 mm.   The cell chamber for artificial organs according to claim 1 or 2, wherein the bottom of the concave portion has a continuous curved shape.   The said board | substrate contains the stem cell storage part formed on one surface of the base part and this base part, The said through-hole and the said recessed part are any one of Claims 1-3 formed in the said stem cell storage part A cell chamber for an artificial organ according to one item.   The cell chamber for artificial organs according to claim 4, further comprising a cover member that covers the stem cell storage unit.   The stem cell storage portion includes a wall surface extending upward from the pedestal portion, and a stem cell storage surface in which the through hole and the recess are formed, and the stem cell storage surface is closer to the pedestal side than a surface connecting the top of the wall surface. The cell chamber for artificial organs according to claim 4 or 5, wherein a space is formed between the stem cell storage surface and the top of the wall surface by being positioned. The cell chamber for artificial organs according to any one of claims 4 to 6, wherein an insertion hole for inserting a means for fixing the cell chamber to a body tissue is formed in the pedestal portion.