Enriched Peripheral Blood-Derived Mononuclear Cells for Treating Knee Osteoarthritis

Abstract

Osteoarthritis (OA) is a common chronic skeletal disease in the elderly. There is no effective therapy to reverse disease severity and knee OA (KOA) progression, particularly at the late stage. This study aims to examine the effect of peripheral blood-derived mononuclear cells (PBMNCs) on pain and motor function rescue in patients with Kellgren–Lawrence (KL) grade II to IV KOA. Participants received one intra-articular (IA) injection of autologous PBMNCs. The mononuclear cells were isolated from peripheral blood, enriched by a specialized medium (MoFi medium), and separated by Ficoll-Paque solution. The isolated and enriched PBMNCs could differentiate into M1 and M2 macrophages in vitro. The in vivo anti-inflammatory effect of the PBMNCs was similar to that of bone marrow mesenchymal stem cells, evaluated by complete Freund’s adjuvant-induced arthritis in rodents. A single-arm and open-label pilot study showed that patients’ knee pain and motor dysfunction were significantly attenuated after the cell transplantation, assessed by visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 12 months post-treatment. Notably, the therapeutic effect of the PBMNCs treatment can be stably maintained for 24 months, as revealed by the KOOS scores. These preclinical and pilot clinical data suggest that IA injection of MoFi-PBMNCs might serve as a novel medical technology to control the pain and the progress of KOA.

Intra-articular bone marrow mononuclear cell therapy improves lameness from naturally occurring equine osteoarthritis

“…A single dose of BMNC lasted more than 12 months, was considered superior to 3 weekly injections of hyaluronan, and demonstrated clinical improvement in 96% of BMNC-treated patients ( 42 , 43 ). Intra-articular injection of enriched peripheral blood-derived mononuclear cells, an alternate source of anti-inflammatory macrophages, showed significant improvements in knee pain and Knee injury and Osteoarthritis Outcome Score for up to 24 months in a recent clinical trial in people ( 62 ). BMNC have the advantage of providing a much higher proportion of macrophage progenitors (40–70%) compared to peripheral blood mononuclear cells (10–19%).…”

The application of exosomes in the early diagnosis and treatment of osteoarthritis

“…Therefore, a sensitive diagnostic modality for early-stage OA and an effective treatment to counteract the progression of early-stage OA are major concerns for patients and health insurance systems. In recent decades, a variety of biological therapy has been proposed to treat earlystage OA, e.g., stem cell therapy (McGonagle et al, 2017;Murphy et al, 2020), platelet-rich plasma (Raeissadat et al, 2021), functional biomaterials (Chuang et al, 2023), and tissue engineering technology (Chuang et al, 2023;Duan et al, 2023). Although the above treatments exhibited great therapeutic potential, also have inevitable limitations respectively.…”

Identifying transcriptomic profiles of iron–quercetin complex treated peripheral blood mononuclear cells from healthy volunteers and diabetic patients

“…Peripheral blood mononuclear cells (PBMCs) encompass a diverse population of immune cells, including lymphocytes (T cells, B cells, and NK cells) and monocyte-derived progenitor cells, which are promising for restoring damaged tissues and promoting regeneration. Their significance lies in their versatile functionality, which ranges from immune responses to regenerative properties 7 , 8 . PBMCs exhibit considerable promise in tissue repair mechanisms, as they actively engage in angiogenesis, tissue remodeling, and wound healing processes.…”