WO2015146405A1 - Platelet production device and platelet production method - Google Patents

Abstract

Provided are a platelet production device and a platelet production method, whereby platelets can be efficiently produced. Specifically speaking, the platelet production device comprises: a platelet production chamber (5) that is a container storing a megakaryocyte-containing liquid; a feed pump (4) that is both a feeding means feeding a liquid culture medium, said liquid culture medium being the megakaryocyte-containing liquid, to the platelet production chamber (5) and an external force-applying means applying an external force, said external force being generated by the flow of the liquid culture medium, to megakaryocytes and thus allowing the megakaryocytes to produce platelets; and a retention member (6) that is a retaining means provided in a part of the platelet production chamber (5) for retaining the megakaryocytes using a nucleated cell-trapping material (8) capable of trapping nucleated cells.

Description

Platelet production apparatus and platelet production method

The present invention relates to a platelet production apparatus and a platelet production method. More specifically, the present invention relates to an apparatus and method for producing platelets from megakaryocytes derived from iPS cells.

Conventionally, platelets are separated from blood by a centrifugal separation method using a difference in specific gravity. For example, it is like patent document 1. The centrifugal separator described in Patent Document 1 is provided for each specific gravity of each blood cell in the blood storage space formed at the outer edge of the centrifugal bowl by rotating the centrifugal bowl of the centrifuge into which blood has flowed at high speed. , Separated into plasma layer, buffy coat layer and red blood cell layer. Then, the platelets are separated from the buffy coat layer by centrifugation.

On the other hand, when platelets are produced from megakaryocytes derived from iPS cells, it is necessary to remove megakaryocytes, which are nucleated cells remaining after platelet production without producing platelets. However, since the specific gravity of megakaryocytes and platelets is close, in order to separate megakaryocytes and platelets by centrifugation, it is necessary to add a large centrifugal acceleration. For this reason, even if megakaryocytes and platelets can be separated by the centrifugal separation method, there is a problem that the ratio of platelets destroyed by a large centrifugal acceleration increases and the platelet recovery rate decreases.

JP-A-9-108594

An object of the present invention is to provide a platelet production apparatus and a platelet production method capable of efficiently producing platelets.

The problems to be solved by the present invention are as described above. Next, means for solving the problems will be described.

That is, the present invention provides a container for storing a liquid containing megakaryocytes, a supply means for supplying a liquid containing megakaryocytes in a container, and a material provided in a part of the container and having a capability of capturing nucleated cells. A holding means for holding the megakaryocyte; and an external force applying means for producing platelets by applying an external force to the megakaryocyte held by the holding means.

In the present invention, the holding means is configured so that a liquid containing megakaryocytes flows along the surface of the material.

In the present invention, the external force applying means applies an external force to the megakaryocyte by a fluid flow.

In the present invention, megakaryocytes are held by a material capable of capturing nucleated cells, and force is applied to the megakaryocytes from the outside to produce platelets from the megakaryocytes.

As the effects of the present invention, the following effects are obtained.

In the present invention, since platelets are produced while holding megakaryocytes, the step of separating megakaryocytes and platelets is omitted. Thereby, platelets can be produced efficiently.

In the present invention, the force applied to the megakaryocyte is set to an arbitrary value, and the path is configured so that the time required for the megakaryocyte to flow along the surface of the material having nucleated cell capturing ability is increased. Since the area where the material and the megakaryocyte are in contact with each other increases and the opportunity for the material and the megakaryocyte to contact with each other increases, the megakaryocyte is easily captured by the material. Thereby, platelets can be produced efficiently.

Schematic which shows the whole structure of the platelet production apparatus which concerns on 1st embodiment of this invention. (A) The conceptual diagram which shows the structure of the holding member in the platelet production apparatus which concerns on 1st embodiment of this invention (b) The conceptual diagram which shows the other structure of a holding member similarly. (A) The schematic diagram which shows the state which the megakaryocyte contacted the holding member in the platelet production apparatus which concerns on 1st embodiment of this invention (b) Similarly, the state where the megakaryocyte adhered to the nucleated cell capture | acquisition material of a holding member is shown. Schematic diagram (c) Schematic diagram showing a state in which megakaryocytes are also producing platelets. Schematic which shows the whole structure of the platelet production apparatus which concerns on 2nd embodiment of this invention. (A) The conceptual diagram which shows the structure of the holding member in the platelet production apparatus which concerns on 2nd embodiment of this invention (b) The conceptual diagram which similarly shows the other structure of a holding member. The schematic diagram which shows the state in which the megakaryocyte is producing platelets in the platelet production apparatus which concerns on 2nd embodiment of this invention. Schematic which shows the whole structure of the platelet production system containing the platelet production apparatus which concerns on this invention.

First, the platelet production apparatus 1 which is the first embodiment of the platelet production apparatus according to the present invention will be described with reference to FIGS. 1 and 2. In each of the following embodiments, each member constituting the platelet production device is made of an appropriate material from the application and strength among non-reactive polymer, biocompatible metal, glass and the like unless otherwise specified. Yes. Specifically, examples of the non-reactive polymer include acrylonitrile polymers such as acrylonitrile butadiene styrene terpolymer, halogenated polymers such as polyvinyl chloride, polyamide, polyimide polycarbonate, polyethylene, polypropylene, and polystyrene. Examples of the biocompatible metal include stainless steel, titanium, platinum and alloys thereof, and cobalt chromium alloy.

As shown in FIG. 1, the platelet production apparatus 1 produces and collects platelets from megakaryocytes. The platelet production apparatus 1 includes a storage tank 2, a circulation channel 3, a supply pump 4, a platelet production chamber 5, and a holding member 6.

The storage tank 2 holds a liquid containing mature megakaryocytes and platelets produced from the mature megakaryocytes (hereinafter simply referred to as “culture medium”). The storage tank 2 is configured to be able to supply a culture solution from the outside. Specifically, the storage tank 2 is connected to a culture device 13 and the like which will be described later, and is configured to be supplied with a culture solution manufactured by the culture device 13 and the like.

The circulation channel 3 is a channel for circulating the culture solution. The circulation channel 3 is composed of a tube made of a non-reactive polymer, a biocompatible metal, glass or the like. The circulation channel 3 is configured to connect the storage tank 2 and the platelet production chamber 5 via the supply pump 4. The circulation channel 3 is configured to connect the platelet production chamber 5 and the storage tank 2. That is, the culture solution in the storage tank 2 is configured to be supplied to the platelet production chamber 5 through the circulation channel 3 by the supply pump 4. The culture solution supplied to the platelet production chamber 5 passes through a platelet production channel 7 described later and is discharged from the platelet production chamber 5 and then returned to the storage tank 2 again through the circulation channel 3. Has been.

The supply pump 4 serving as a supply means and an external force applying means supplies the culture solution in the storage tank 2 to the circulation channel 3. Although the supply pump 4 is comprised, for example from a roller pump or a continuous syringe pump, it is not limited to this. The supply pump 4 is provided in the middle of the circulation channel 3. Thus, the supply pump 4 is configured to circulate the culture solution between the storage tank 2 and the platelet production chamber 5 by supplying the culture solution in the storage tank 2 to the circulation channel 3. The supply pump 4 is configured so that the culture solution can be supplied to the circulation channel 3 at an arbitrary flow rate. In the present embodiment, the platelet production device 1 is configured to supply the culture solution by the supply pump 4, but is not limited thereto.

The platelet production chamber 5, which is a container, constitutes a space for producing platelets from megakaryocytes. The platelet production chamber 5 is a container formed from a non-reactive polymer or a biocompatible metal. The platelet production chamber 5 is provided in the middle of the circulation channel 3. That is, the platelet production chamber 5 is supplied with the culture solution from the storage tank 2 from the supply port 5a to which the circulation channel 3 is connected, and from the discharge port 5b to which the circulation channel 3 is connected. The culture medium is returned to the storage tank 2.

As shown in FIGS. 1 and 2, the holding member 6 as a holding means holds a megakaryocyte. The holding member 6 is formed of a thin plate made of a non-reactive polymer or a biocompatible metal. The holding member 6 is provided inside the platelet production chamber 5. The surface of the holding member 6 is coated with a nucleated cell capturing material 8 that is a material having a high ability to capture nucleated cells. That is, the nucleated cell capturing material 8 provided on the surface of the holding member 6 is configured to contact the culture solution containing megakaryocytes inside the platelet production chamber 5. In the present embodiment, the holding member 6 has a nucleated cell capturing material 8 applied on the surface thereof, but is not limited thereto, and the nucleated cell capturing material 8 is vapor-deposited or nucleated. A sheet or the like made of the cell trapping material 8 may be provided on the surface of the holding member 6. Further, the holding member 6 itself may be composed of the nucleated cell capturing material 8.

As the nucleated cell capturing material 8, synthetic polymers such as polyethylene, polypropylene, polystyrene, acrylic resin, nylon, polyester, polycarbonate, polyacrylamide, polyurethane, agarose, cellulose, cellulose acetate, chitin, chitosan, alginate, etc. Examples thereof include inorganic materials such as natural polymers, hydroxyapatite, glass, alumina, and titania, and metals such as stainless steel, titanium, and aluminum. In addition, these capture materials can be used as they are, but they may be subjected to surface modification as necessary, for example, to increase platelet permeability or to selectively capture cells. For example, in order to increase the platelet permeability, there can be mentioned a method of coating a polymer having a nonionic hydrophilic group and a basic nitrogen-containing functional group proposed in WO 87/05812.

As shown in FIG. 2A, the holding member 6 is arranged inside the platelet production chamber 5 so as to constitute a platelet production flow path 7 from the culture solution supply port 5a to the culture solution discharge port 5b. Yes. The holding member 6 constitutes the wall surface of the platelet production channel 7. That is, in the platelet production flow path 7, the nucleated cell capturing material 8 is applied to the surface of the holding member 6 constituting the wall surface. The platelet production channel 7 is configured to have a size that allows platelets and megakaryocytes contained in the culture medium to sufficiently pass therethrough. The size of megakaryocytes derived from iPS cells varies depending on the culture process. Therefore, it is desirable to determine the size of the platelet production channel 7 based on the size of the megakaryocyte at that time.

Specifically, as shown in FIG. 2A, as an embodiment of the arrangement mode of the holding member 6, a plurality of holding members 6 are arranged in the platelet production chamber 5 so as to be adjacent to each other. Among the plurality of holding members 6, the first holding member 6 is arranged so as to partition one side and open the platelet production chamber 5. The second holding member 6 adjacent to the first holding member 6 is arranged so as to partition the platelet production chamber 5 by opening the other side. That is, the plurality of holding members 6 are arranged in the platelet production chamber 5 so that the opening positions of the adjacent holding members 6 do not overlap. Thereby, in the platelet production chamber 5, a platelet production channel 7 from the culture solution supply port 5 a to the culture solution discharge port 5 b is formed so as to meander by the plurality of holding members 6. In other words, the holding member 6 makes the nucleated cell longer by making the time for the culture solution to flow along the nucleated cell capturing material 8 applied to the surface of the holding member 6 constituting the wall surface of the platelet production channel 7 as long as possible. Since the area where the capturing material 8 and the megakaryocyte are in contact with each other increases and the opportunity for the nucleated cell capturing material 8 and the megakaryocyte to contact with each other is increased, the amount of megakaryocytes captured by the nucleated cell capturing material 8 is increased. It is configured to let you.

As shown in FIG. 2 (b), as another embodiment of the arrangement mode of the holding member 6, a plurality of holding members 6 are provided from the culture solution supply port 5a of the platelet production chamber 5 to the culture solution discharge port 5b. You may arrange | position so that the platelet production chamber 5 may be partitioned toward it. Thus, in the platelet production chamber 5, a plurality of platelet production channels 7 extending from the culture solution supply port 5 a to the culture solution discharge port 5 b are configured by a plurality of adjacent holding members 6. That is, the holding member 6 is configured to increase the amount of megakaryocytes captured by the nucleated cell capturing material 8 by increasing the total amount of the culture solution that passes through the platelet production channel 7 per unit time as much as possible. ing.

In the present embodiment, the cross-sectional shape of the platelet production channel 7 constituted by the holding member 6 is not limited. For example, a circular shape, a rectangular shape, an elliptical shape, or the like in which the nucleated cell capturing material 8 is provided on the inner diameter. You may form in the pipe | tube which consists of these cross-sectional shapes. Further, the size and number of the holding members 6 provided in the platelet production chamber 5 are not particularly limited as long as they do not hinder the flow of the culture solution in the platelet production chamber 5.

The platelet production device 1 configured as described above is configured such that the culture solution in the storage tank 2 is supplied from the supply port 5a to the inside of the platelet production chamber 5 through the circulation channel 3 by the supply pump 4. FIG. 2 (a) see thick arrows). Furthermore, the platelet production apparatus 1 is configured such that the culture solution supplied to the platelet production chamber 5 is discharged from the discharge port 5 b to the storage tank 2 through the circulation channel 3. That is, the platelet production apparatus 1 is configured so that the culture solution circulates between the storage tank 2 and the platelet production chamber 5.

Next, the embodiment of the platelet production method in the platelet production apparatus 1 will be specifically described with reference to FIGS.

As shown in FIG. 1, the platelet production apparatus 1 supplies the culture solution in the storage tank 2 to the circulation channel 3 by the supply pump 4. Thereby, the megakaryocytes contained in the culture solution and the platelets already produced from the megakaryocytes are supplied to the platelet production chamber 5 through the circulation channel 3. The culture solution supplied from the supply port 5a to the platelet production chamber 5 flows into the platelet production flow path 7 (see FIG. 2) configured inside the platelet production chamber 5.

As shown in FIG. 3 (a), megakaryocytes that have flowed into the platelet production flow path 7 of the platelet production chamber 5 together with the culture solution flow along the surface of the holding member 6 (nucleated cell capturing material 8). Some megakaryocytes A contact the holding member 6. Then, as shown in FIG. 3B, the megakaryocyte A that has contacted the holding member 6 is captured by adhering to the nucleated cell capturing material 8 applied to the surface of the holding member 6. The force with which the nucleated cell capturing material 8 holds the megakaryocyte A is determined by the area of the portion where the megakaryocyte is in contact with the nucleated cell capturing material 8. Further, in the megakaryocyte A, a force to be separated from the nucleated cell capturing material 8 is generated by the flow of the culture solution. The force for separating the megakaryocyte A from the nucleated cell capturing material 8 is determined by the flow rate of the culture solution supplied by the supply pump 4 and the size of the megakaryocyte A. That is, the contact area with the nucleated cell capturing material 8 necessary for the megakaryocyte A to be captured by the nucleated cell capturing material 8 is determined from the flow rate of the culture solution supplied by the supply pump 4 and the size of the megakaryocyte A. Determined. When the contact area with the nucleated cell capturing material 8 is larger than the contact area necessary for capturing the megakaryocyte A, the megakaryocyte A is captured by the nucleated cell capturing material 8 and held by the holding member 6. On the other hand, since the platelets supplied to the platelet production chamber 5 together with the culture solution are anucleated cells, they are not captured by the nucleated cell capturing material 8 even if they contact the holding member 6.

Among megakaryocytes contained in the culture solution, megakaryocytes that were less than the contact area required for capturing the contact area with the megakaryocyte that did not contact the holding member 6 and the nucleated cell-capturing material 8 (see FIG. 3) is discharged together with the culture solution from the platelet production chamber 5 and returned to the storage tank 2. Similarly, the platelets contained in the culture solution are discharged from the platelet production chamber 5 together with the culture solution and returned to the storage tank 2. The megakaryocytes and platelets returned to the storage tank 2 are supplied again to the platelet production chamber 5 through the circulation channel 3 together with other megakaryocytes and platelets by the supply pump 4.

As shown in FIG. 3 (b), the megakaryocyte A held by the holding member 6 is flowed from the culture solution passing through the platelet production channel 7 by the supply pump 4 serving as an external force applying means. (See FIGS. 3B and 3C, thin arrows). Only the force due to the flow of the culture solution supplied by the supply pump 4 is applied to the megakaryocyte A held by the holding member 6. Therefore, the platelet production apparatus 1 can control the force applied to the megakaryocyte A by controlling the flow rate of the supply pump 4. In the megakaryocyte A pushed in the flow direction of the culture solution, shear stress is generated at a location where a force due to the flow of the culture solution is applied.

As shown in FIG. 3 (c), in the megakaryocyte A, a part of cytoplasm forming the megakaryocyte A is sheared starting from a location where shear stress is generated by the flow of the culture solution. That is, the megakaryocyte A is partly separated by force due to the flow of the culture solution, and platelets C are produced. The produced platelets are mixed in the culture solution and discharged from the platelet production chamber 5 together with the culture solution, and then conveyed to the storage tank 2 through the circulation channel 3.

The megakaryocytes held on the holding member 6 continue to produce platelets while the force due to the flow of the culture solution is applied. Megakaryocytes separated from the holding member 6 stop producing platelets and are discharged from the platelet production chamber 5 together with the culture solution and returned to the storage tank 2. In addition, megakaryocytes held again by the holding member 6 in the platelet production channel 7 resume production of platelets. The megakaryocytes and platelets discharged from the platelet production chamber 5 and returned to the storage tank 2 are again supplied to the platelet production channel 7 of the platelet production chamber 5 through the circulation channel 3 together with other megakaryocytes and platelets by the supply pump 4. Supplied.

With this configuration, the platelet production device 1 produces platelets by applying a force due to the flow of the culture solution to the megakaryocytes held by the holding member 6. Furthermore, since the platelet production apparatus 1 eliminates megakaryocytes by producing platelets from megakaryocytes contained in the culture solution, the step of separating megakaryocytes and platelets contained in the culture solution is omitted. Moreover, the platelet production apparatus 1 is set so that a force appropriate for the production of platelets is applied to the megakaryocyte by controlling the flow rate of the supply pump 4. Furthermore, the platelet production apparatus 1 increases the area where the nucleated cell capturing material 8 and the megakaryocyte are in contact with each other as the megakaryocytes flow along the surface of the nucleated cell capturing material 8. Opportunities for contact increase and megakaryocytes are more likely to be captured by the material. Thereby, the platelet production apparatus 1 can produce platelets efficiently.

Hereinafter, the platelet production apparatus 10 in the second embodiment of the platelet production apparatus according to the present invention will be described with reference to FIGS. 4 and 5. In the following embodiments, the same points as those of the above-described embodiments will not be specifically described, and different portions will be mainly described.

As shown in FIG. 4, the platelet production apparatus 10 includes a storage tank 2, a circulation channel 3, a supply pump 4, a platelet production chamber 5, and a holding member 11.

The configuration for circulating the culture solution of the platelet production device 10 is the same as the configuration of the platelet production device 1 according to the first embodiment described above.

As shown in FIG. 4, the holding member 11 which is a holding means holds a megakaryocyte. The holding member 11 is formed by laminating a nonwoven fabric or a mesh material made of a non-reactive polymer or a biocompatible metal. The holding member 11 is provided inside the platelet production chamber 5. The surface of the holding member 11 is coated with a nucleated cell capturing material 8 that is a material having a high ability to capture nucleated cells. That is, the nucleated cell capturing material 8 provided on the surface of the holding member 11 is configured so that megakaryocytes contained in the culture solution are in contact with each other inside the platelet production chamber 5. In this embodiment, the holding member 11 is coated with the nucleated cell capturing material 8 on the surface thereof, but is not limited to this. The nucleated cell capturing material or the nucleated cell capturing material is not limited to this. A non-woven fabric made of the material 8 or a mesh-like material may be used.

The holding member 11 is made of a non-woven fabric or a mesh-like material having a gap that is large enough to allow platelets and megakaryocytes to pass sufficiently. That is, the holding member 11 is intended to separate the megakaryocyte from the relationship between the size of the megakaryocyte and the gap, unlike a general filter that separates the object using the relationship between the gap and the size of the object. do not do. The size of megakaryocytes derived from iPS cells varies depending on the culture process. Therefore, it is desirable to determine the size of the gap between the nonwoven fabric and the net-like material based on the size of the megakaryocyte at that time.

Specifically, as shown in FIG. 5A, the holding member 11 is formed by laminating a plurality of nonwoven fabrics or mesh-like materials in a plate shape, and between the supply port 5a and the discharge port 5b of the platelet production chamber 5. One or more platelets are arranged so as to partition the platelet production chamber 5. Thereby, the platelet production chamber 5 is configured such that all the culture solution supplied from the supply port 5 a passes through the holding member 11. Further, as shown in FIG. 5B, the holding member 11 may be configured to be formed in an accordion shape in order to increase the surface area in the platelet production chamber 5. That is, the holding member 11 is configured to increase the amount of megakaryocytes captured by the nucleated cell capturing material 8 by increasing the time during which the culture solution passes through the vicinity of the nucleated cell capturing material 8. ing.

The platelet production apparatus 10 configured as described above is configured such that the culture solution in the storage tank 2 is supplied to the platelet production chamber 5 through the circulation channel 3 by the supply pump 4 (FIG. 5A). See arrow). Furthermore, the platelet production apparatus 1 is configured such that all of the culture solution supplied to the platelet production chamber 5 passes through the holding member 11 and is then discharged to the storage tank 2 through the circulation channel 3. That is, the platelet production device 1 is configured such that the culture solution circulates between the storage tank 2 and the platelet production chamber 5 while passing through the holding member 11.

Next, the embodiment of the platelet production method in the platelet production apparatus 10 will be specifically described with reference to FIGS.

As shown in FIG. 4, the platelet production apparatus 1 supplies the culture solution in the storage tank 2 to the circulation channel 3 by the supply pump 4. Thereby, the megakaryocytes contained in the culture solution and the platelets already produced from the megakaryocytes are supplied to the platelet production chamber 5 through the circulation channel 3.

As shown in FIG. 5 (a), all the culture solution supplied from the supply port 5 a to the platelet production chamber 5 passes through the holding member 11. As shown in FIG. 6, some megakaryocytes A come into contact with the holding member 11 (nucleated cell capturing material 8) when the megakaryocytes contained in the culture solution pass through the holding member 11. The megakaryocyte A in contact with the holding member 11 is captured by adhering to the nucleated cell capturing material 8 applied to the surface of the holding member 11. On the other hand, since the platelets supplied to the platelet production chamber 5 together with the culture solution are anucleated cells, they are not captured by the nucleated cell capturing material 8 even if they contact the holding member 11 (nucleated cell capturing material 8).

The megakaryocyte A held on the holding member 11 is separated from a part of its cytoplasm by the force of the flow of the culture solution to produce platelet C. Of the megakaryocytes contained in the culture solution, the contact area with the megakaryocytes that did not contact the holding member 11 and the nucleated cell capturing material 8 is less than the contact area necessary for being captured by the nucleated cell capturing material 8. The megakaryocytes that have been passed through the holding member 11 together with the culture medium are discharged from the platelet production chamber 5 and returned to the storage tank 2 (megakaryocytes B in FIG. 6). Similarly, platelets contained in the culture solution pass through the holding member 11 together with the culture solution and are discharged from the platelet production chamber 5 and returned to the storage tank 2. The megakaryocytes and platelets returned to the storage tank 2 are supplied again to the platelet production chamber 5 through the circulation channel 3 together with other megakaryocytes and platelets by the supply pump 4.

With this configuration, the platelet production apparatus 1 produces platelets by applying force (see thin arrows in FIG. 6) to the megakaryocytes held by the holding member 11 due to the flow of the culture solution. Furthermore, since the platelet production apparatus 1 eliminates megakaryocytes by producing platelets from megakaryocytes contained in the culture solution, the step of separating megakaryocytes and platelets contained in the culture solution is omitted. Moreover, the platelet production apparatus 1 is set so that a force appropriate for the production of platelets is applied to the megakaryocyte by controlling the flow rate of the supply pump 4. Furthermore, the platelet production apparatus 1 increases the chance that megakaryocytes contact the nucleated cell-capturing material 8 according to the number and shape of the holding member 11, and the megakaryocytes are easily captured by the material. Thereby, the platelet production apparatus 1 can produce platelets efficiently.

As shown in FIG. 7, the platelet production apparatus according to the first embodiment and the second embodiment described above cultivates megakaryocyte progenitor cells derived from iPS cells under predetermined conditions to produce mature megakaryocytes. A culture device 13, a detection device 13 comprising an in-liquid particle counter for detecting the amount of megakaryocytes in the culture solution, a dust separation device 14 for removing megakaryocyte nuclei and DNA from the recovery solution, and recovered platelets You may comprise as the platelet production system 12 which comprises the concentration apparatus 15 which concentrates. By comprising in this way, a platelet formulation can be continuously manufactured from the megakaryocyte precursor cell induced | guided | derived from the iPS cell.

DESCRIPTION OF SYMBOLS 1 Platelet production apparatus 4 Supply pump 5 Platelet production chamber 6 Holding member 8 Nucleated cell capture | acquisition material

Claims (4)

A container for storing a liquid containing megakaryocytes,
Supply means for supplying a liquid containing megakaryocytes in a container;
A holding means which is provided in a part of the container and holds megakaryocytes by a material capable of capturing nucleated cells;
An external force applying means for applying an external force to the megakaryocytes held by the holding means to produce platelets;
A platelet production apparatus comprising: The platelet production apparatus according to claim 1, wherein the holding means is configured such that a liquid containing megakaryocytes flows along the surface of the material. The platelet production apparatus according to claim 1 or 2, wherein the external force applying means applies an external force to the megakaryocyte by a fluid flow. A platelet production method in which megakaryocytes are held by a material capable of capturing nucleated cells, and force is applied to the megakaryocytes from the outside to produce platelets from the megakaryocytes.

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