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A clinical study for treatment of articular cartilage damage in knee joints with allogeneic induced pluripotent stem (iPS) cell-derived cartilage. (TACK-iPS)

Development of treatment of knee articular cartilage damage with iPS-cell-derived cartilage. (Development of treatment of knee articular cartilage damage with iPS-cell-derived cartilage.)

Takaori Akifumi

Dec. 22, 2023

4

Average age at surgery:59(43-70), 1 male, 3 females. The cartilage injury site was the femoral medial condyle in all four cases. Preoperative Kellgren-Lawrence grade was grade I in one case, grade II in one case, and grade 0 in two cases. Arthroscopy at the time of implantation revealed an ICRS grade of grade 3 in all four cases.

All four cases with knee cartilage injuries who agreed to participate in this study were deemed eligible and enrolled, and underwent allogeneic iPS cell-derived cartilage transplantation without postponement.During the observation period, one case was discontinued from this study at the physician's discretion due to an adverse event, and three cases completed the study after undergoing the prescribed observation and examination up to 12 months postoperatively. None of the transplanted iPS cell-derived cartilage was removed.

One adverse event unrelated to this study was reported after 6 months postoperatively.This case was discontinued from the present study at the physician's decision.

CT of the knee joint showed no destruction of bone structure or bone augmentation of iPS cell-derived cartilage transplantation area. MRI of the knee joint also showed no evidence of tumorigenesis of iPS cell-derived cartilage. In addition, whole-body CT showed no possibility of metastasis due to tumor formation of iPS cell-derived cartilage. In a 3D-MOCART evaluation using MRI at 6 months postoperatively, all four cases had successful engraftment of allogeneic iPS cell-derived cartilage with native cartilage. Arthroscopy was performed in three cases at 12 months postoperatively and showed cartilage repair in all cases; two cases improved from grade 3 to grade 2 and one case improved from grade 3 to grade 1 based on ICRS classification. Biopsy-based assessment of articular cartilage regeneration at 12 months postoperatively was also performed in three cases, particularly with OsScore Tissue morphology scores of 3 points (Hyaline) in two cases and 2 points (Hyaline/fibrocartilage) in one case. In the average preoperative and 1-year postoperative scores of KOOS as case-reported outcome measures, symptoms and stiffness score improved from 73 preoperatively to 94 postoperatively, pain score from 67 preoperatively to 89 postoperatively, function (daily living) score from 83 preoperatively to 88 postoperatively, function (sports and recreational activities) score from 38 preoperatively to 50 postoperatively, and quality of life score from 41 preoperatively to 58 postoperatively.

Allogeneic iPS cell-derived cartilage is potentially at risk for tumorigenesis, but no neoplastic growths were observed at 12 months after iPS cartilage transplantation. Therefore, the safety of iPS cell-derived cartilage transplantation in humans was confirmed. Improvements in postoperative clinical, imaging, arthroscopic, and histologic evaluation scores were also observed, suggesting that iPS cell-derived cartilage transplantation might be a useful treatment for knee articular cartilage damage.

https://jrct.niph.go.jp/latest-detail/jRCTa050190104

Matsuda Shuichi

Kyoto University Hospital

54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

seikei@kuhp.kyoto-u.ac.jp

Kuriyama Shinichi

Kyoto University Hospital

54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

+81-75-751-3366

seikei@kuhp.kyoto-u.ac.jp

Interventional

single arm study

open(masking not used)

historical control

single assignment

treatment purpose

1) Patients with knee articular cartilage damage of grade III of Cartilage Repair Society (ICRS) articular cartilage injury classification diagnosed by arthroscopy or MRI.
2) Patients with knee articular cartilage damage with the size of 1-5 cm2 in total.
3) Patients who is aged between 20 and 70 when they consent.
4) Patients who have consent in the form of document.
5) Patients whose cartilage damage can be assessed by MRI at the time of screening.

1) Patients who has or had malignant tumorswith cancer.
2) Patients who got damage or undergo the surgery as follows less than six weeks ago.
Ligament reconstruction in knee ligament (such as anterior cruciate ligament and posterior cruciate ligament) injury.
Meniscal suture or partial resection for meniscal injuries.
Around knee osteotomy in the lower limb alignment abnormality.
3) Patients who are scheduled for other surgeries of the lower limbs throughout this study, except prior surgery for comorbidities in this study or protocol treatment.
4) Patients who are impossible to undergo the postoperative rehabilitation due to abnormalities in the opposite lower limb
5) Patients with serious allergy to ingredients (e.g. bovine serum and/or rosuvastatin) which used for producing iPS cell-derived chondrocytes and fibrin glue in this study.
6) Patients with active infections.
7) Serious complications (e.g., heart disease, chronic respiratory disease, liver and kidney failure, uncontrolled diabetes, and hypertension) that may influence the conduct and evaluation of this study.
8) Patients who are pregnant, possibly pregnant, breast-feeding or wiling to be pregnant.
9) Patients with psychiatric disorders that may influence the conduct and evaluation of this study.
10) Patients whom the doctors considered inappropriate for the study.

Both

Damage of articular cartilage of the Knee

The patient is put under general or lumber anesthesia. After arthroscopic observation, skin and joint capsule are incised and the lesion is exposed and debrided to create defect. The defect is filled with allogeneic iPS cell-derived cartilage, which are fixed with sealants such as fibrin glue or covered with periosteum.

Articular cartilage damage,Articular cartilage disorder,osteoarthritis

Safety
1) Frequency and rate of adverse event
2) Presence or absence of tumorigenicity

1) Local CT at two weeks after surgery to assess the status of subchondral bone and trabecular bone
2) Whole body CT at 12 months after surgery to assess the probability of metastasis when transplanted cartilage get malignancy
3) MRI at baseline, 2 weeks, 3 months, 6 months and 12 months after surgery to assess the size, repair rate and homogeneity of the repair tissue
4) Local X-ray at baseline, 2 weeks, 3 months, 6 months and 12 months after surgery to assess the osteoarthritic change of the knee joint by using KL (Kellgren-Lawrence) grade
5) Arthroscopy at 12 months after surgery to evaluate the quality of repair tissue by using ICRS grades
6) Biopsy at 12 months after surgery to evaluate the regeneration of articular cartilage
7) Improvement of Knee injury and Osteoarthritis Outcome Score (KOOS) and Lysholm Knee Score at 1 year postoperatively

Complete

+81-75-753-4680

Oct. 15, 2019