Associations of clinical outcomes and MRI findings in intra-articular administration of autologous adipose-derived stem cells for knee osteoarthritis

Higuchi, Junya; Yamagami, Ryota; Matsumoto, Takumi; Tomohiro, Terao; Inoue, Keita; Tsuji, Shinsaku; Maenohara, Yuji; Matsuzaki, Takashi; Chijimatsu, Ryota; Omata, Yasunori; Yano, Fumiko; Tanaka, Sakae; Saito, Taku

doi:10.1016/j.reth.2020.04.003

Cited by 20 publications

(8 citation statements)

References 33 publications

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“…For knee OA treatment, intra-articular injection of MSCs, including bone marrow-derived stem cells (BMSCs) and adipose-derived stem cells (ADSCs), has been proven to be a safe therapy [ 3 ]. Studies have shown that intra-articular injection of BMSCs is effective in improving joint function and decreasing knee OA symptoms [ 4 , 5 ]; injection of ADSCs also improves VAS and KOOS-sports/recreation in OA patients [ 6 ]. Moreover, MSCs therapies could preserve articular cartilage superficial layer cells, inhibit synovitis [ 7 ], and relieve vascular infiltration of subchondral bone [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression

Yang

Wang

Fan

et al. 2022

Bioactive Materials

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Intra-articular injection of mesenchymal stem cells (MSCs) is a promising strategy for osteoarthritis (OA) treatment. However, more and more studies reveal that the injected MSCs have poor adhesion, migration, and survival in the joint cavity. A recent study shows that tropoelastin (TE) regulates adhesion, proliferation and phenotypic maintenance of MSCs as a soluble additive, indicating that TE could promote MSCs-homing in regenerative medicine. In this study, we used TE as injection medium, and compared it with classic media in MSCs intra-articular injection such as normal saline (NS), hyaluronic acid (HA), and platelet-rich plasma (PRP). We found that TE could effectively improve adhesion, migration, chondrogenic differentiation of infrapatellar fat pad MSCs (IPFP-MSCs) and enhance matrix synthesis of osteoarthritic chondrocytes (OACs) in indirect-coculture system. Moreover, TE could significantly enhance IPFP-MSCs adhesion via activation of integrin β1, ERK1/2 and vinculin (VCL) in vitro . In addition, intra-articular injection of TE-IPFP MSCs suspension resulted in a short-term increase in survival rate of IPFP-MSCs and better histology scores of rat joint tissues. Inhibition of integrin β1 or ERK1/2 attenuated the protective effect of TE-IPFP MSCs suspension in vivo . In conclusion, TE promotes performance of IPFP-MSCs and protects knee cartilage from damage in OA through enhancement of cell adhesion and activation of integrin β1/ERK/VCL pathway. Our ﬁndings may provide new insights in MSCs intra-articular injection for OA treatment.

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Section: Introductionmentioning

confidence: 99%

Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression

Yang

Wang

Fan

et al. 2022

Bioactive Materials

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“…Studies examining clinical outcomes after injecting in vitro expanded autologous AD-MSCs and BM-MSCs are grouped in Table 2 . 60 – 77 Table 3 includes clinical studies examining allogeneic cell therapies. 31 , 78 – 84 Traditionally, BM-MSCs have been the phenotype chosen for OA because of their superior chondrogenic potential when compared to those of adipose origin.…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal stromal cell products for intra-articular knee injections for conservative management of osteoarthritis

Andı́a

Maffulli

2021

Therapeutic Advances in Musculoskeletal

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Sports injuries and secondary joint problems, mainly of the knee, are common, especially in sports associated with high impact activities and/or torsional loading. The consequences can be career ending in elite athletes and reduce exercise activities in recreational people. Various cell products can be injected intra-articularly. First, fresh cellular mixtures can be prepared and injected in the same day, such as stromal vascular fraction of adipose tissue (SVF) and bone marrow concentrates (BMCs). Second, autologous mesenchymal stromal cells (MSCs) can be isolated from BMCs or SVF and, after several weeks of laboratory expansion, several millions of MSCs can be obtained for intra-articular injection. Finally, allogeneic MSCs from the bone marrow, adipose tissue or perinatal tissues of selected donors constitute an ‘off-the-shelf’ experimental treatment for injection delivery in patients with osteoarthritis of the knee. The perceived efficacy of all these products is based on the hypothesis of a paracrine mechanism of action: when living cells are delivered within the joint, they establish a molecular cross-talk with immune cells and local cell phenotypes, thereby modulating inflammation with subsequent modifications in the catabolic/degenerative milieu. Current clinical research examines whether injection delivery of MSCs translates into actual clinical benefits. Overall, clinical studies lack the quality needed to answer major research questions, including clinical and structural efficacy, optimal cell dose, and number of injections and specific protocol for cell delivery. Poor experimental designs are exacerbated by the diversity of patient phenotypes that hinder comparisons between treatments. Further understanding of disease pathology is paramount to develop potent function assays and understand whether the host tissue, the cell product or both should be primed before MSCs are injected intra-articularly.

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“…The most direct correlation between BML and clinical symptoms is pain, and intolerable pain is often the immediate cause of patients seeking medical treatment. A 6-month retrospective study [ 44 ] showed that the pretreatment presence of BML was also associated with daily activities and function in the short term, suggesting that BML is more responsive to PASS regardless of pain or function. Since preoperative cartilage factors are not influential factors in prognosis for clinical failure, we believe that sufficient attention should be given to BML severity in serial MRI slices, as this may imply a higher risk of failure with the treatment of SVF.…”

Section: Discussionmentioning

confidence: 99%

Mid-term prognosis of the stromal vascular fraction for knee osteoarthritis: a minimum 5-year follow-up study

Zhang

et al. 2022

Stem Cell Res Ther

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Background The short-term safety and efficacy of stromal vascular fraction (SVF) in treating knee osteoarthritis (KOA) have been extensively studied but the mid-term and long-term prognoses remain unknown. Methods 126 KOA patients were recruited and randomly assigned to SVF group and hyaluronic acid (HA) group (control group). The scores of visual analogue scale (VAS) and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were assessed and compared between the two groups 1, 2, 3, and 5 years after treatment. The endpoint was defined as surgeries related to KOA or clinical scores exceeding the patient acceptable symptom state (PASS). Results The VAS and WOMAC scores in the SVF group were significantly better than those in the HA group during the 5-year follow-up after treatment. The average responsive time to SVF treatment (61.52 months) was significantly longer than HA treatment (30.37 months). The adjusted Cox proportional hazards model showed that bone marrow lesion (BML) severity, body mass index (BMI) and treatment were independent risk factors and that the use of SVF reduced the risk of clinical failure by 2.602 times. The cartilage volume was reduced in both the SVF and control groups at 5 years but reduced less in the SVF group. Conclusions Up to 5 years after SVF treatment, acceptable clinical state was present for approximately 60% of patients. BML severity and BMI were independent predictors of the prognosis. Trial Registry: This study was retrospectively registered at Chinses Clinical Trial Registry with identifier ChiCTR2100052818 and was approved by ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University, number 2013-X-063.

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Associations of clinical outcomes and MRI findings in intra-articular administration of autologous adipose-derived stem cells for knee osteoarthritis

Cited by 20 publications

References 33 publications

Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression

Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression

Mesenchymal stromal cell products for intra-articular knee injections for conservative management of osteoarthritis

Mid-term prognosis of the stromal vascular fraction for knee osteoarthritis: a minimum 5-year follow-up study

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