Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics

Filardo, Giuseppe; Madry, Henning; Jelić, Mislav; Roffi, Alice; Cucchiarini, Magali; Kon, Elizaveta

doi:10.1007/s00167-012-2329-3

Cited by 213 publications

(177 citation statements)

References 84 publications

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“…1); five case studies (17,(22)(23)(24)(25)(26) were excluded and nine studies (24,(27)(28)(29)(30)(31)(32)(33)(34) were removed due to difficulties in extracting the outcome measurements. Four systematic reviews (35)(36)(37)(38) were also excluded. An assessment of the remaining 18 studies revealed that 10 used a single-arm prospective design (18)(19)(20)(39)(40)(41)(42)(43)(44)(45), four used quasi-experimental trials (46)(47)(48)(49) and four used RCT (50-53) (Table I).…”

Section: Study Characteristicsmentioning

confidence: 99%

Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis

Cui

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. To assess the clinical efficacy and safety of mesenchymal stem cell (MSC) treatment for osteoarthritis of the knee (KOA), a systematic electronic literature search was performed on PubMed, EMBASE and Web of Science. Studies published in English from the earliest record to December 2014 were searched using the following keywords: Cartilage defect, cartilage repair, osteoarthritis, KOA, stem cells, MSCs, bone marrow concentrate (BMC), adipose-derived mesenchymal stem cells, synovial-derived mesenchymal stem cells and peripheral blood-derived mesenchymal stem cells. The effect sizes of selected studies were determined by extracting pain scores from the visual analog scale and functional changes from International Knee Documentation Committee and Lysholm and Western Ontario and McMaster Universities Osteoarthritis Index before and after MSCs or reference treatments at 3, 6, 12, and 24 months. The factors were analyzed and the outcomes were modified after comparing the MSC group pooled values with the pretreatment baseline or between different treatment arms. A systematic search identified 18 clinical trials on this topic, including 10 single-arm prospective studies, four quasi-experimental studies and four randomized controlled trials that used BMCs to treat 565 patients with KOA in total. MSC treatment in patients with KOA showed continual efficacy for 24 months compared with their pretreatment condition. Effectiveness of MSCs was improved at 12 and 24 months post-treatment, compared with at 3 and 6 months. No dose-responsive association in the MSCs numbers was demonstrated. However, patients with arthroscopic debridement, activation agent or lower degrees of Kellgren-Lawrence grade achieved improved outcomes. MSC application ameliorated the overall outcomes of patients with KOA, including pain relief and functional improvement from basal evaluations, particularly at 12 and 24 months after follow-up.

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Section: Study Characteristicsmentioning

confidence: 99%

Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis

Cui

Wang

et al. 2016

Experimental and Therapeutic Medicine

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“…MSCs may be useful for this purpose as they are readily present within the bone marrow of adults in addition to being a precursor cell type to the chondrocytic lineage. 18,25 Further, bone marrow MSCs have been shown to maintain stemness and chondrogenic differentiation capacity upon expansion in vitro allowing sufficient cell numbers for use in tissue engineering practices. 23,26 However, previous studies have shown that while MSCs do undergo chondrogenesis, less matrix is produced by MSCs than by chondrocytes cultured similarly.…”

Section: Introductionmentioning

confidence: 99%

Cell-Derived Polymer/Extracellular Matrix Composite Scaffolds for Cartilage Regeneration, Part 1: Investigation of Cocultures and Seeding Densities for Improved Extracellular Matrix Deposition

Levorson

Mountziaris

et al. 2014

Tissue Engineering Part C: Methods

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This study investigated the coculture of chondrocytes and mesenchymal stem cells (MSCs) on electrospun fibrous polymer scaffolds to produce polymer/extracellular matrix (ECM) hybrid constructs with the objective of reducing the number of chondrocytes necessary to produce ample cartilage-like ECM within the scaffolds. To generate these hybrid constructs, electrospun poly(e-caprolactone) fibrous scaffolds were seeded at both high and low initial densities with five different ratios of chondrocytes to MSCs: 1:0, 1:1, 1:3, 1:5, and 0:1, and cultured for 7, 14, and 21 days. Glycosaminoglycan production and distribution within the three coculture groups was similar to quantities generated by chondrocyte-only controls. Conversely, as the concentration of chondrocytes was increased, the collagen content of the constructs also increased at each time point, with a 1:1 chondrocyte to MSC ratio approximating the collagen production of chondrocytes alone. Histological staining suggested that cocultured constructs mimicked the well-distributed ECM patterns of chondrocyte generated constructs, while improving greatly over the restricted distribution of matrix within MSC-only constructs. These results support the capacity of cocultures of chondrocytes and MSCs to generate cartilaginous matrix within a polymeric scaffold. Further, the inclusion of MSCs in these cocultures enables the reduction of chondrocytes needed to produce cell-generated ECM.

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“…[24] Other studies have shown that BMSC has a stronger ability of chondrogenic differentiation than ADSC. Filardo et al [26] reviewed 90 research papers on the clinical application of ADSC chondrogenic differentiation, including 72 preclinical studies and 18 clinical experiments. Only 2 clinical experiments recommended ADSC.…”

Section: Application Of Chondrogenic Differentiationmentioning

confidence: 99%

Advances in the research of basic study and clinical application of adipose-derived mesenchymal stem cells

Sheng-jun

Wang

et al. 2018

DCC

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Since the discovery of adipose-derived mesenchymal stem cell (ADSC) in more than ten years, a great progress has been made from its basic research to clinical application. Compared with bone marrow mesenchymal stem cells, ADSC is more abundant in reserve, easier to obtain with fewer injuries and less complications. These cells have multiple differentiation potential and can differentiate into adipocytes, chondrocytes and osteoblasts with the influence of different inducing factors. Early studies of ADSC mainly focused on the ability of multi-directional differentiation, especially on the regeneration of bone defects and cartilage tissue. At present, the researches mainly focus on immunoregulation and paracrine function of ADSC. Although ADSC has made a great progress in clinical application, the cell preparation, use pattern, and mechanisms in clinical treatment are not clear. This paper elaborates on these issues.

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Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics

Abstract: IV.

Cited by 213 publications

References 84 publications

Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis

Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis

Cell-Derived Polymer/Extracellular Matrix Composite Scaffolds for Cartilage Regeneration, Part 1: Investigation of Cocultures and Seeding Densities for Improved Extracellular Matrix Deposition

Advances in the research of basic study and clinical application of adipose-derived mesenchymal stem cells

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