Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study

Background: Knee osteoarthritis is the most common musculoskeletal progressive disorder that affects nearly 303 million people worldwide. This condition prevails in 10% males and 13% females among the elders above 60. Although there is conventional nonsurgical and surgical treatment available for knee osteoarthritis, there is a fascinating interest in bone marrow aspirate concentrate (BMAC) as well as adipose-derived mesenchymal stem cells (AD-MSC), including enzymatically treated stromal vascular fraction (SVF) and mechanically treated (microfat/nanofat) injections among physicians. Hence, this systematic review aims to determine the efficacy of BMAC and AD-MSCs (enzyme and mechanically treated) injections for knee osteoarthritis treatment. Methods: A systematic review was performed on the following data sources (PubMed, Scopus, Google Scholar, EMBASE, and Cochrane Library) published on March 31, 2021. The keywords or MeSH terms include 'Knee Osteoarthritis with 'Bone marrow aspirate concentrate' OR 'BMAC' or with 'Adipose-derived mesenchymal stem cells (AD-MSC)' or with 'Stromal vascular fraction' OR 'SVF' or 'Mechanically treated AD-MSC (mfat/nanofat)'. In addition, the retrieved articles were further reviewed to identify relevant research studies. Results: The authors reviewed and tabulated data based on the year of study, study type, therapy protocol, patient population, outcome measures, and interpretation. Among the 382 records screened, 43 studies (16 on BMAC and 27 on AD-MSCs) were included in the systematic review study. Among them, only 5 were randomized controlled trials. These selected studies demonstrated short-term positive outcomes such as improvement in knee pain and function with no adverse side effects. Moreover, researchers reported varied administration methods of BMAC or AD-MSC either as standalone or in combination with other conservative procedures such as PRP (Platelets Rich Plasma), HA (Hyaluronic acid), or surgery. Conclusions: BMAC and AD-MSC (enzymatically and mechanically treated) injections prove safer and more efficacious in patients with knee osteoarthritis for a shorter duration of 2 years. However, the available literature lacks high-quality studies with no varied clinical settings and long-term follow-up of more than two years.

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Treatment of chondral defects of the knee with one step matrix-assisted technique enhanced by autologous concentrated bone marrow: In vitro characterisation of mesenchymal stem cells from iliac crest and subchondral bone

Injury ◽

10.1016/j.injury.2010.09.027 ◽

2010 ◽

Vol 41 (11) ◽

pp. 1172-1177 ◽

Cited By ~ 73

Author(s):

Laura de Girolamo ◽

Giulia Bertolini ◽

Matteo Cervellin ◽

Gabriella Sozzi ◽

Piero Volpi

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Subchondral Bone ◽

Iliac Crest ◽

Chondral Defects ◽

Concentrated Bone Marrow ◽

One Step

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In step with contemporary trends-stem-celltherapy as a key driver of regenerative orthopedics at the Clinical Center of Vojvodina - preliminary data for the treatment of knee osteoarthritis and osteochondral lesions

Medicinski pregled ◽

10.2298/mpns16s1077d ◽

2016 ◽

Vol 69 (suppl. 1) ◽

pp. 77-84

Author(s):

Oliver Dulic ◽

Ivica Lalic ◽

Natasa Janjic ◽

Predrag Rasovic ◽

Gordan Gavrilovic ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Visual Analogue Scale ◽

Knee Osteoarthritis ◽

Analogue Scale ◽

Visual Analogue Scale Pain ◽

Osteochondral Lesions ◽

Analogue Scale Pain

Introduction. In the treatment of various orthopedic conditions, regenerativetherapies, including platelet rich plasma and autologous stem-cell therapy, have recently been advancing. Knee cartilage lesions are a debilitating disease resulting in fibrillation and subsequent degradation which can also involve the subchondral bone and lead to the development of osteoarthritis. Bone marrow mesenchymal stem cells are a heterogeneous mixture of cells involved in cartilage formation and regenerative repair, whereas other mesenchymal stem cells have the capacity to play a role as immunomodulatory and trophic factors. Nowadays, stem-cell therapy is widely used for the treatment of knee osteoarthritis and cartilage lesions. The purpose of this study was to evaluate preliminary clinical data of treatment of knee osteoarthritis with stem cell injection and treatment of osteochondral lesions with stem-cell scaffold. Material and Methods. Stem cells were obtained by concentrating the content taken with aspiration needles from the bone marrow my means of Arthrex Angel Bone Marrow Aspirate Concentrate centrifuge. Results. The study sample consisted of 39 patients who were included in knee osteoarthritis treatment. Surgical implantation was performed in 7 patients from the osteochondral group. In the first group, an average Visual Analogue Scale pain felt before intervention decreased statistically significantly three days after the intervention (from 7.27 to 2.12, p?0.05) and remained 1.2 until the check-up after 3 months. The same results were achieved in the average Western Ontario and McMaster Universities Arthritis Index score (prior to intervention = 51.5; after 1 month = 72 and after 3 months = 76). For the second group, an average preintervention Visual Analogue Scale pain decreased statistically significantly three days after intervention (from 8.1 to 2.7) and remained 1.2 until the check-up after months. The same results were achieved on the Knee injury and Osteoarthritis Outcome Score pain (p?0.05). Both procedures were proved as safe providing pain relief and function improvement of treated knee joints.

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Osteogenic ability of rat bone marrow concentrate is at least as efficacious as mesenchymal stem cells in vitro

Journal of Biomedical Materials Research Part B Applied Biomaterials ◽

10.1002/jbm.b.34340 ◽

2019 ◽

Vol 107 (8) ◽

pp. 2500-2506 ◽

Cited By ~ 2

Author(s):

Yusuke Kohno ◽

Tzuhua Lin ◽

Jukka Pajarinen ◽

Monica Romero‐Lopez ◽

Masahiro Maruyama ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Marrow Concentrate ◽

Rat Bone

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Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions?

Arthritis Research & Therapy ◽

10.1186/s13075-019-2014-8 ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 5

Author(s):

Jean-Marie Berthelot ◽

Benoit Le Goff ◽

Yves Maugars

Keyword(s):

Rheumatoid Arthritis ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Ankylosing Spondylitis ◽

Animal Models ◽

Subchondral Bone ◽

Frequent Relapses ◽

Marrow Mesenchymal Stem Cells ◽

Bone Cortex

Abstract Background Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might conversely fuel synovitis and enthesitis. Main text Abnormal behaviour of BM-MSCs and/or their progeny has been found in RA and SpA. BM-MSCs also contribute to the ossifying processes observed in ankylosing spondylitis. Some synovial fibroblastic stem cells probably derive from BM-MSCs, but some stem cells can also migrate through the bare zone area of joints, not covered by cartilage, into the synovium. BM-MSCs can also migrate in the synovium over tendons. Sub-populations of bone marrow stem cells also invade the soft tissue side of enthesis via small holes in the bone cortex. The present review aims (1) to make a focus on these two aspects and (2) to put forward the hypothesis that lasting epigenetic changes of some BM-MSCs, induced by transient infections of the bone marrow close to the synovium and/or entheses (i.e. trained immunity of BM-MSCs and/or their progeny), contribute to the pathogenesis of inflammatory rheumatisms. Such hypothesis would fit with (1) the uneven distribution and/or flares of arthritis and enthesitis observed at the individual level in RA and SpA (reminiscent of what is observed following reactive arthritis and/or in Whipple’s disease); (2) the subchondral bone marrow oedema and erosions occurring in many RA patients, in the bare zone area; and (3) the frequent relapses of RA and SpA despite bone marrow transplantation, whereas most BM-MSCs resist graft preconditioning. Conclusion Some BM-MSCs might be more the problem than the solution in inflammatory rheumatisms. Subchondral bone marrow BM-MSCs and their progeny trafficking through the bare zone area of joints or holes in the bone cortex of entheses should be thoroughly studied in RA and SpA respectively. This may be done first in animal models. Mini-arthroscopy of joints could also be used in humans to specifically sample tissues close to the bare zone and/or enthesis areas.

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Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study

BioMed Research International ◽

10.1155/2016/4868613 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 22

Author(s):

Mikel Sánchez ◽

Diego Delgado ◽

Pello Sánchez ◽

Emma Muiños-López ◽

Bruno Paiva ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Synovial Fluid ◽

Knee Joint ◽

Knee Osteoarthritis ◽

Subchondral Bone ◽

Platelet Rich Plasma ◽

Joint Function ◽

Novel Approach ◽

New Strategy

The aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovial membrane, superficial articular cartilage, synovial fluid, and subchondral bone by combining intra-articular injections and intraosseous infiltrations of platelet rich plasma. We explored a new strategy consisting of intraosseous infiltrations of platelet rich plasma into the subchondral bone in combination with the conventional intra-articular injection in order to tackle several knee joint tissues simultaneously. We assessed the clinical outcomes through osteoarthritis outcome score (KOOS) and the inflammatory response by quantifying mesenchymal stem cells in synovial fluid. There was a significant pain reduction in the KOOS from baseline(61.55±14.11)to week 24(74.60±19.19), after treatment(p=0.008), in the secondary outcomes (symptoms,p=0.004; ADL,p=0.022; sport/rec.,p=0.017; QOL,p=0.012), as well as VAS score (p<0.001) and Lequesne Index(p=0.008). The presence of mesenchymal stem cells in synovial fluid and colony-forming cells one week after treatment decreased substantially from7.98±8.21 MSC/μL to4.04±5.36 MSC/μL(p=0.019)and from601.75±312.30to139.19±123.61 (p=0.012), respectively. Intra-articular injections combined with intraosseous infiltrations of platelet rich plasma reduce pain and mesenchymal stem cells in synovial fluid, besides significantly improving knee joint function in patients with severe knee osteoarthritis. This trial is registered on EudraCT with the number2013-003982-32.

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