Kidney transplant kit

Abstract

To provide a renal transplantation kit suitable for treatment of Potter syndrome.SOLUTION: The present invention provides a renal transplantation kit for a human fetus with Potter syndrome, the renal transplantation kit having a renal placode with a bladder derived from a porcine embryo.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a kidney transplantation kit.

Background Art

[0002] Potter syndrome is a syndrome that causes oligohydramnios due to bilateral renal agenesis or hypoplasia, resulting in pulmonary hypoplasia and limb deformities. Fetuses suffering from Potter syndrome have difficulty in postnatal management due to pulmonary hypoplasia.

[0003] Potter syndrome is caused not only by bilateral renal agenesis, hypoplasia, and dysplasia, but also by bilateral severe congenital hydronephrosis, polycystic kidney disease, multicystic dysplastic kidney, Renal Tubular Dysgenesis, etc. The incidence is reported to be 1 in 5,000 to 10,000 births, but it is difficult to accurately grasp the frequency because there are many cases of stillbirth or death immediately after birth, and 40% of them result in stillbirth.

[0004] As a treatment method for fetuses or neonates with Potter syndrome, artificial amniotic fluid injection therapy can be mentioned during the fetal period, and artificial respiration management, nitric oxide inhalation therapy, ECMO, peritoneal dialysis, etc. can be mentioned during the neonatal period (see, for example, Patent Document 1).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] However, even using the method described in Patent Document 1, it is difficult to treat fetuses or neonates with Potter syndrome, and further improvement is required. Therefore, an object of the present invention is to provide a kidney transplantation kit that is suitably used for the treatment of Potter syndrome.

Means for Solving the Problems

[0007] The present invention includes the following embodiments. [1] A kidney transplant kit for human fetuses suffering from Potter syndrome, comprising a kidney primordium with a bladder derived from a pig fetus. [2] The kidney transplant kit according to [1], wherein the kidney primordium with bladder derived from a pig fetus is injected through the mother's amniotic cavity into the kidney-equivalent area of ​​the human fetus. [3] The human fetus is 14 to 20 weeks gestation, as described in [1] or [2], a kidney transplant kit. [4] The kidney transplant kit described in any one of [1] to [3], wherein the kidney primordium with bladder is derived from a wild-type pig fetus. [5] The kidney transplant kit described in any one of [1] to [4], wherein the kidney primordium with bladder is derived from a pig fetus at 4 to 7 weeks of gestation. [6] A kidney transplant kit that does not contain immunosuppressants, as described in any one of [1] to [5]. [7] A kidney transplant kit described in any one of [1] to [6], further comprising a kit for detecting viruses that cause zoonotic diseases. [Effects of the Invention]

[0008] According to the present invention, a kidney transplant kit suitable for use in the treatment of Potter syndrome can be provided. [Brief explanation of the drawing]

[0009] [Figure 1] This photograph shows a puncture needle (catheter needle) being inserted into the kidney of a pig fetus through the mother's amniotic fluid cavity. [Figure 2] This photograph shows the result of injecting fluorescently labeled kidney cells into the kidney-like region of a mouse fetus. [Modes for carrying out the invention]

[0010] Kidney transplant kit In one embodiment, the present invention provides a kidney transplant kit for a human fetus suffering from Potter syndrome, comprising a kidney primordium with a bladder derived from a pig fetus.

[0011] The kidney primordium refers to the fetal kidney, which in mammals corresponds to the metanephrocyte. In fetal mammals, a tissue is formed in which the bladder, ureter, and metanephrocyte are integrated; in this specification, this is called a kidney primordium with a bladder. The inventors have named this fetal bladder-ureter-metanephrocyte tissue a cloaca graft. In other words, in this specification, the kidney primordium with a bladder is also called a cloaca graft. When the kidney primordium is transplanted into the abdominal cavity of an animal, blood vessels invade the cloaca from the recipient, development continues, and urine is produced.

[0012] The kidney primordium with bladder is preferably derived from a pig fetus at 4-7 weeks of gestation (28-49 days). A pig fetus at 45 days of gestation is approximately the same size as a human fetus at 16 weeks of gestation. Using kidneys from this fetal stage makes it easier for them to mature into urine-producing kidney tissue without differentiating into other tissues. Furthermore, human fetuses exhibit immune tolerance until 14-20 weeks of gestation, making them capable of engrafting kidney primordia derived from pig fetuses. After transplantation, blood vessels derived from the human fetus integrate into the kidney primordia.

[0013] The kidney primordium with bladder is preferably derived from a wild-type pig fetus. In this invention, genetically modified pigs are not required; clean pig kidney primordium with bladder is sufficient. Furthermore, iPS cells are not required. Therefore, this invention is not subject to regulations on genetically modified animals or iPS cells. Moreover, immunosuppressants are not required in this invention.

[0014] If a transplanted kidney can produce urine, it contributes to amniotic fluid production, and effectiveness can be expected even if the transplanted kidney lacks the ability to remove uremic toxins or endocrine functions. Therefore, effects can be expected in the short period until birth. Also, because human fetuses have a small body weight, even a small amount of urine can be expected to be effective.

[0015] Furthermore, the kit of the present invention preferably includes an injection device for injecting a kidney primordium with bladder derived from a fetal pig. Such an injection device preferably includes introducers for the outer sheath and the inner needle, a delivery system, and a shunt tube. Such an injection device is used as follows. First, a introducer needle composed of an outer sheath and an inner needle is percutaneously inserted through the amniotic cavity of the mother to the fetal retroperitoneal cavity. Next, the inner needle is removed, and a delivery system containing a kidney primordium with bladder derived from a fetal pig is inserted into the remaining lumen of the outer sheath. After injecting the kidney primordium with bladder derived from a fetal pig by hydraulic pressure, the delivery system is removed. When urine is produced and the allantoic vesicle is confirmed 2 - 5 weeks later, puncture again under echography and insert a shunt tube to connect the allantoic vesicle and the amniotic cavity with the inner shunt. By such a procedure, urine produced by the kidney primordium with bladder derived from a fetal pig is discharged into the amniotic cavity.

[0016] In addition, the kit of the present invention preferably further includes a detection kit for causative viruses of zoonotic infectious diseases. Examples of the detection kit for causative viruses of zoonotic infectious diseases include a porcine endogenous retrovirus detection kit. Regarding porcine endogenous retrovirus (PERV), PERV - A and PERV - B are integrated into the genes of all pigs, and PERV - C is integrated into the genes of some pigs. Since PERV - A, PERV - B, and PERV - A / C recombinants can infect human cultured cells, it is preferable to monitor the presence or absence of PERV infection in human fetuses after transplantation or neonates after birth. Examples of the detection kit include those containing antibodies against PERV, or those containing primers and / or probes for detecting the genome of PERV.

[0017] ≪Treatment method≫ In one embodiment, the present invention provides a method for treating a kidney, comprising: step (a) of transplanting a kidney primordium with bladder derived from a fetal pig to a location corresponding to the kidney of a human fetus suffering from Potter syndrome using an injection device; and step (b) of placing a shunt tube from the fetal allantoic vesicle to the maternal amniotic cavity to allow urine produced from the transplanted kidney to flow into the amniotic cavity.

[0018] By leaving the transplanted material transplanted in the above step (a) for a predetermined period, a kidney primordium with a bladder derived from a fetal pig grows and starts urine production. The predetermined period may be, for example, 1 to 10 weeks.

[0019] Subsequently, step (b) is carried out simultaneously with the transplantation. Furthermore, if the kidney primordium with a bladder derived from a fetal pig is removed at the time of peritoneal dialysis catheter insertion after birth, it is easier to ensure safety.

Example

[0020] Hereinafter, the present invention will be described by way of examples, but the present invention is not limited to the following examples.

[0021] [Experimental Example 1] E45 fetal pigs correspond to the size of a 16-week-old human fetus. Using this pregnant pig, a puncture needle was inserted through the amniotic cavity of the mother into the location corresponding to the kidney of the fetal pig (see Fig. 1). It was confirmed that the puncture needle could accurately pierce the location corresponding to the kidney of the fetus.

[0022] [Experimental Example 2] Fetuses at E15 were taken out from pregnant mice, and after injecting fluorescently labeled kidney cells into the location corresponding to the kidney of the fetuses, the fetuses were returned to the uterus of the mice and the abdomen was closed (see Fig. 2). It was confirmed that the injected kidney cells had engrafted in the location corresponding to the kidney of the born mice.

Industrial Applicability

[0023] According to the present invention, a kidney transplantation kit suitably used for the treatment of Potter syndrome can be provided.

Claims

1. A kidney transplant kit for human fetuses suffering from Potter syndrome, comprising a kidney primordium with a bladder derived from a pig fetus.

2. The kidney transplant kit according to claim 1, wherein the kidney primordium with bladder derived from a pig fetus is injected through the mother's amniotic fluid cavity into the kidney-equivalent area of ​​the human fetus.

3. The kidney transplant kit according to claim 1 or 2, wherein the human fetus is 14 to 20 weeks pregnant.

4. The kidney transplant kit according to any one of claims 1 to 3, wherein the kidney primordium with bladder is derived from a wild-type pig fetus.

5. The kidney transplant kit according to any one of claims 1 to 4, wherein the kidney primordium with bladder is derived from a pig fetus at 4 to 7 weeks of gestation.

6. A kidney transplant kit according to any one of claims 1 to 5, which does not contain an immunosuppressant.

7. Furthermore, the kidney transplant kit according to any one of claims 1 to 6 further comprises a kit for detecting viruses that cause zoonotic diseases.

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