Alterations in cartilage quantification before and after injections of mesenchymal stem cells into osteoarthritic knees

Ichiro Sekiya,Hisako Katano,Makoto Tomita,Nobutake Ozeki,Jun Masumoto,Mitsuru Mizuno,Hideyuki Koga

doi:10.1038/s41598-021-93462-8

Ichiro Sekiya, Hisako Katano + Show 5 more

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https://doi.org/10.1038/s41598-021-93462-8

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Abstract

Several studies have reported improvement in knee pain following mesenchymal stem cell (MSC) injections for knee osteoarthritis (OA). We developed a novel 3D magnetic resonance imaging (MRI) analysis software program that provides “projected cartilage area ratios” for automatic detection of changes in cartilage amounts. The primary objective of this prospective interventional study was to compare alterations in the projected cartilage area ratio (thickness ≥ 1.5 mm) at the femoral posteromedial region between 30 weeks before and 30 weeks after synovial MSC injections. Secondary objectives were to assess the clinical scores and safety of MSC injections. Patients with OA who complained of knee pain underwent autologous synovial MSC injections into the knee at time 0 and again 15 weeks later. MRI examinations were performed at − 30, − 15, − 1, and 30 weeks. Patients showing < 3% decreases in the projected cartilage area ratio (thickness ≥ 1.5 mm) at the femoral the posteromedial region from − 30 weeks to − 15 weeks were excluded from the study. The Lysholm Knee Score, Knee Injury and Osteoarthritis Outcome Scale (KOOS), and Numerical Rating Scale (NRS) scores were evaluated at − 30, − 15, − 5, − 2, 0, 5, 10, 15, 20, 25, and 30 weeks. Five patients were excluded because 3D MRI analysis showed no cartilage loss at − 15 weeks. Ultimately, eight OA patients underwent MSC injections. The projected cartilage area ratio significantly decreased by 0.07 in the 30 weeks before MSC injections (p = 0.01), but no further decreases occurred in the 30 weeks after MSC injections. The projected cartilage area ratio at the femoral posteromedial region showed a significant difference between 30 weeks before and 30 weeks after MSC injections. The Lysholm Knee Score, KOOS, and NRS values improved significantly after the injections. MSC injection could not be ruled out as the cause of two adverse events: transient knee pain and itching in both hands. Fully automatic 3D MRI analysis showed that synovial MSC injections suppressed cartilage loss in patients with progressive OA.Trial registration: Intraarticular injections of synovial stem cells for osteoarthritis of the knee (Number UMIN 000026732). Date of registration; June 1, 2017. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029967.

Highlights

Abbreviations mesenchymal stem cells (MSCs) Mesenchymal stem cell OA Osteoarthritis KOOS Knee Injury and Osteoarthritis Outcome Scale NRS Numerical Rating Scale MRI Magnetic resonance imaging
Some reports have described improved MRI results following intraarticular MSC injections; the MRI evaluations used in previous studies have included procedures such as Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART)[6,7], one-slice evaluations using 2D images[8,9], and semiautomatic 3D a nalysis[10], and these procedures might not be sufficiently objective or reliable
Some clinical reports have evaluated intra-articular injections of MSCs derived from intra-articular tissues, but those MSCs were derived only from the infrapatellar fat pad (IFP)[12]

Summary

Introduction

Abbreviations MSC Mesenchymal stem cell OA Osteoarthritis KOOS Knee Injury and Osteoarthritis Outcome Scale NRS Numerical Rating Scale MRI Magnetic resonance imaging. Magnetic resonance imaging (MRI) can directly evaluate the articular cartilage, making this imaging technique useful for understanding the pathological condition of osteoarthritis (OA) of the knee. The cartilage area was extracted semi-automatically and required manual correction We have overcome this limitation by improving the software so that it allows fully automatic extraction of the cartilage area using deep neural networks, followed by application of the projected cartilage area ratio to the tibial cartilage[2]. The purpose of the current prospective interventional study was to compare the alterations in the projected cartilage area ratio (thickness ≥ 1.5 mm) at the femoral posteromedial region between 30 weeks before and 30 weeks after synovial MSC injections. The underlying hypothesis for this study was that MSC injections would inhibit the cartilage loss that occurs in the progressive OA knee

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Conclusion