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Polydactyly-derived allogeneic chondrocyte cell-sheet transplantation with high tibial osteotomy as regenerative therapy for knee osteoarthritis.

ABSTRACT: Allogeneic cell therapies are not fully effective in treating osteoarthritis of the knee (OAK). We recently reported that transplantation of autologous chondrocyte cell-sheets along with open-wedge high tibial osteotomy promoted hyaline cartilage repair in humans. Here we describe our regenerative therapy for OAK using polydactyly-derived allogeneic chondrocyte cell-sheets (PD sheets) and temperature-responsive culture inserts. Ten patients with OAK and cartilage defects categorized arthroscopically as Outerbridge grade III or IV received the therapy. Cartilage viscoelasticity and thickness were assessed before and after transplantation. Arthroscopic biopsies obtained 12 months after transplantation were analyzed histologically. Gene expression was analyzed to evaluate the PD sheets. In this small initial longitudinal series, PD sheet transplantation was effective in treating OAK, as indicated by changes in cartilage properties. Gene marker sets in PD sheets may predict outcomes after therapy and provide markers for the selection of donor cells. This combined surgery may be an ideal regenerative therapy with disease-modifying effects in OAK patients.

SUBMITTER: Hamahashi K

PROVIDER: S-EPMC9755241 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Polydactyly-derived allogeneic chondrocyte cell-sheet transplantation with high tibial osteotomy as regenerative therapy for knee osteoarthritis.

Hamahashi Kosuke K Toyoda Eriko E Ishihara Miya M Mitani Genya G Takagaki Tomonori T Kaneshiro Nagatoshi N Maehara Miki M Takahashi Takumi T Okada Eri E Watanabe Ayako A Nakamura Yoshihiko Y Kato Reiko R Matoba Ryo R Takagi Takehiko T Akutsu Hidenori H Umezawa Akihiro A Kobayashi Hiroyuki H Akamatsu Tadashi T Yamato Masayuki M Okano Teruo T Watanabe Masahiko M Sato Masato M

NPJ Regenerative medicine 20221216 1

Allogeneic cell therapies are not fully effective in treating osteoarthritis of the knee (OAK). We recently reported that transplantation of autologous chondrocyte cell-sheets along with open-wedge high tibial osteotomy promoted hyaline cartilage repair in humans. Here we describe our regenerative therapy for OAK using polydactyly-derived allogeneic chondrocyte cell-sheets (PD sheets) and temperature-responsive culture inserts. Ten patients with OAK and cartilage defects categorized arthroscopic ...[more]

PMID: 36522336

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Project description:BackgroundHigh tibial osteotomy (HTO) has been used for over 60 years in clinical practice and mainly comprises two major techniques: closed wedge high tibial osteotomy (CWHTO) and open wedge high tibial osteotomy (OWHTO). However, these have been gradually replaced by total knee arthroplasty (TKA), due to inconsistent clinical results and many complications. With the concept of knee-protection and ladder treatment of osteoarthritis, as an effective minimally invasive treatment for knee osteoarthritis, HTO has once again received attention.MethodsA systematic literature search was conducted in PubMed, Embase, ClinicalKey, CNKI, and the China Wanfang database. The search terms relating to osteoarthritis and high tibial osteotomy were used. Studies were considered eligible if the participants were adults with knee osteoarthritis (KOA) who had undergone HTO. A total of two reviewers participated in the selection of the studies. Reviewer 1 was assigned to screen titles and abstracts, and reviewer 2 to screen full-text data. Data extraction was completed by reviewer 2, and 30% were checked by the research team. Potential conflicts were resolved through discussion. The methodological quality was assessed using a risk of bias, based on the Cochrane handbook and Newcastle-Ottawa assessment scale. The outcome indicators are (1) posterior slope of tibial plateau, (2) the height of the patella, (3) fracture in the osteotomy plane, (4) survival rate, (5) special surgery knee score (HSS), and (6) the recurrence of varus deformity of the included studies were evaluated according to the guidelines of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) working group (Atkins et al., BMJ 328:1490, 2004).ResultsAmong the 18 articles included, 10 were prospective cohort studies, five were randomized controlled trial (RCT) studies, one was prospective comparative study (PCS), one was retrospective comparative study (RCS), and one was retrospective cohort. The earliest publication year was 1999, and the most recent was 2018. A total of 6555 eligible cases were included, comprised of 3351 OWHTO patients and 3204 CWHTO patients. Five RCT were assessed using risk of bias, based on the Cochrane handbook. Eleven cohort studies and two case-control studies were assessed using the Newcastle-Ottawa assessment scale. These six outcome indicators for a total of twenty-four evidence individuals were evaluated separately, among which the GRADE classification of 1, 2, and 6 was medium quality, and 3, 4, and 5 were low quality. Based on our systematic review, regardless of whether the chosen procedure was OWHTO or CWHTO, both HSS scores increased significantly as compared with the preoperative scores. Compared with CWHTO, the height of the patella and tibial posterior slope angle increased following OWHTO. Additionally, OWHTO has a better long-term survival rate and lower fracture rate, supporting OWHTO as the first treatment choice.ConclusionsFor young patients with knee osteoarthritis (KOA), high tibial osteotomy (HTO) can be considered as a treatment option to replace total knee arthroplasty (TKA) to reduce the economic burden and promote the reasonable allocation of medical resources. This study shows that compared with CWHTO, OWHTO has certain advantages in long-term survival rate and lower fracture rate, but the level of evidence is lower. In the future, we will need larger sample sizes and longer follow-up randomized controlled trials to improve our research.

Project description:BackgroundSpacer-type tibial osteotomy have been proven a novel and effective osteotomy to treat osteoarthritis, while lack of comparison with other surgical methods in younger patients. This study aims to evaluate the short-term clinical outcomes of spacer-type tibial osteotomy versus open wedge high tibial osteotomy (OWHTO) and unicompartmental knee arthroplasty (UKA) for Kellgren-Lawrence (K-L) grade 3-4 osteoarthritis (OA) in patients younger than 65 years.MethodsThis retrospective study analyzed a total of 224 patients with K-L grade 3-4 knee OA treated from March 2018 to November 2020. Three groups were created according to the operation type. The clinical outcomes recorded preoperatively and at 6, 12 and 24 months postoperatively were the range of motion (ROM), visual analogue scale (VAS), American Knee Society Score (KSS), Western Ontario and McMaster Universities Global (WOMAC) score, operation time, length of incision, relevant complications and failures. Radiographic parameters were measured to evaluate the correction of varus deformity.ResultsThe cohort comprised 224 patients; 70 underwent spacer-type tibial osteotomy, 73 underwent OWHTO, and 81 underwent UKA. The spacer group had the shortest incision (P = 0.000), least amount of bleeding (P = 0.000), and shortest operation time (P = 0.000). UKA achieved the most significant pain relief based on VAS (P = 0.014), KSS pain score (0.030), and WOMAC score (P = 0.000) at 6 months postoperatively, but there were no differences between three groups at 12 and 24 months postoperatively. The spacer and OWHTO groups achieved significantly greater ROM changes compared with the UKA group (all P = 0.000). The complication rate did not significantly differ between the three groups. No surgical failures were identified in HTO but two spacer dislocations in spacer group and three polyethylene dislocations in UKA.ConclusionFor younger patients with K-L grade 3-4 OA, OWHTO seems to be the most appropriate method through clinical comparisons. Although spacer-type tibial osteotomy offers shorter operation time and comparable clinical outcomes, it also has extended recovery phase, additional fibular incision and the risk of spacer dislocation, which did not appear to be superior to OWHTO and UKA under the indications outlined in this study.Trial registrationRetrospectively registered, QYFY WZLL 27,021.

Dataset Information

Polydactyly-derived allogeneic chondrocyte cell-sheet transplantation with high tibial osteotomy as regenerative therapy for knee osteoarthritis.

Publications

Polydactyly-derived allogeneic chondrocyte cell-sheet transplantation with high tibial osteotomy as regenerative therapy for knee osteoarthritis.

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