Intra‐Articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof‐of‐Concept Clinical Trial

Abstract

Mesenchymal stem cells (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose-escalation cohorts; the low-dose (1.0 3 10 7 cells), mid-dose (5.0 3 10 7 ), and high-dose (1.0 3 10 8 ) group with three patients each. The phase II included nine patients receiving the high-dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment-related adverse event. The WOMAC score improved at 6 months after injection in the high-dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group. Histology demonstrated thick, hyaline-like cartilage regeneration. These results showed that intra-articular injection of 1.0 3 10 8 AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline-like articular cartilage.

Deformability of Human Mesenchymal Stem Cells Is Dependent on Vimentin Intermediate Filaments

“…Mesenchymal stem cells (MSCs) have recently shown promise as a therapeutic cell 3 source for the treatment of many diseases, including osteoarthritis 1,15 . However, 4 osteoarthritic cartilage presents a challenging environment for therapeutic MSCs, 5 injected systemically or implanted within a biomaterial scaffold, due to the abnormal 6 biochemical and mechanical environment 8,11 .…”

“…Mechanical properties and mechanotransduction are in 12 part regulated by the cytoskeleton, consisting primarily of actin microfilaments, 13 microtubules, and vimentin intermediate filaments (IFs) for cells of mesenchymal 14 lineage 5,7,19,23,24,29,30,34,36 . While their role in the pathogenesis of OA is still unknown, 15 vimentin IFs have recently been found to be disrupted or dispersed in osteoarthritic 16 chondrocytes 4,16 . Notably, vimentin has also been shown to be downregulated in MSCs 17 of osteoarthritic patients 27 , which raises questions about the potential efficacy of 18 autologous stem cell therapies for treatment of OA.…”

“…Our results suggest that a decrease in vimentin IFs paradoxically 13 reduces the deformability of MSCs, potentially due to changes in the manner by which 14 actin microfilaments and microtubules organize and function to resist loads. 15 17 18 hMSC cell culture 19 20 For initial lentiviral construct screening experiments, hMSCs from Lonza (Walkersville,…”

Preliminary Clinical Results With Lipoaspirate Stromal Vascular Cell Fraction in Treatment of Patients With Knee Osteoarthritis

“…Немногочисленные пилотные исследования продемонстрировали хорошую переносимость, безопасность, а также клиническую эффектив-ность СВФ у пациентов с ранними стадиями ДОА [6,13,16,25].…”

Stem cells; mesenchymal stem cells and current clinical applications

“…Sonuçlar do¤rultusunda MKH infüzyonunda yüksek doz uygulamasının yararlı ve etkili oldu¤u vurgulanmıtır. [41] Plastik cerrahide, otolog/allojenik MKH nakilleri, rekonstrüktif ve estetik amaçla sıklıkla kullanılan bir tekniktir. Rigotti ve ark.…”