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Autologous bone marrow mesenchymal cell induced chondrogenesis for the treatment of osteoarthritis of knee.

ABSTRACT: Healthy and high quality of life has become the main issue with increasing human life span. Many biological treatments for osteoarthritis of the knee have been tried with limited success. We compared data from 7 patients who underwent total knee arthroplasty and 46 patients who underwent autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) for osteoarthritis of grade IV of the Kellgren-Lawrence classification and grade IV of modified Outerbridge classification from 50 to 65 years of age. Clinical evaluation of the 2 groups showed significant improvement in the mean telephone Knee Society Scoring system (tKSS)-A (pain) and tKSS-B (function) scores throughout the postoperative follow-up period. There was no difference in the patients' satisfaction between the 2 groups. MCIC is a treatment option at least for delaying disease progression of osteoarthritis of the knee.

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Supplementary material is available for this article at 10.1007/s13770-016-9125-y and is accessible for authorized users.

SUBMITTER: Huh SW

PROVIDER: S-EPMC6170850 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Autologous bone marrow mesenchymal cell induced chondrogenesis for the treatment of osteoarthritis of knee.

Huh Sung Woo SW Shetty Asode Ananthram AA Kim Jang Mook JM Cho Mi-La ML Kim Seon Ae SA Yang Siyoung S Kim Young Ju YJ Javaregowda Palaksha Kanive PK Choi Nam Yong NY Kang Jin J Kim Seok Jung SJ

Tissue engineering and regenerative medicine 20160405 2

Healthy and high quality of life has become the main issue with increasing human life span. Many biological treatments for osteoarthritis of the knee have been tried with limited success. We compared data from 7 patients who underwent total knee arthroplasty and 46 patients who underwent autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) for osteoarthritis of grade IV of the Kellgren-Lawrence classification and grade IV of modified Outerbridge classification from 50 to 65 year ...[more]

PMID: 30603400

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Project description:The production of a clinically useful engineered cartilage is an outstanding and unmet clinical need. High-throughput RNA sequencing provides a means of characterizing the molecular phenotype of populations of cells and can be leveraged to better understand differences among source cells, derivative engineered tissues, and target phenotypes. In this study, small RNA sequencing is utilized to comprehensively characterize the microRNA transcriptomes (miRNomes) of native human neonatal articular cartilage and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) differentiating into cartilage organoids, contrasting the microRNA regulation of engineered cartilage with that of a promising target phenotype. Five dominant microRNAs are upregulated during cartilage organoid differentiation and disproportionately regulate transcription factors: miR-148a-3p, miR-140-3p, miR-27b-3p, miR-140-5p, and miR-181a-5p. Two microRNAs that dominate the miRNomes of hBM-MSCs, miR-21-5p and miR-143-3p, persist throughout the differentiation process and may limit the ability of these cells to differentiate into an engineered cartilage resembling target native articular cartilage. By using predictive bioinformatics tools and antagomir inhibition, these persistent microRNAs are shown to destabilize the mRNA of genes with known or potential roles in cartilage biology including FGF18, TGFBR2, TET1, STOX2, ARAP2, N4BP2L1, LHX9, NFIA, and RPS6KA5. These results shed light on the extent to which only a few microRNAs contribute to the complex regulatory environment of hBM-MSCs for engineered tissues. Impact statement MicroRNAs are emerging as important controlling elements in the differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). By using a robust bioinformatic approach and further validation in vitro, here we provide a comprehensive characterization of the microRNA transcriptomes (miRNomes) of a commonly studied and clinically promising source of multipotent cells (hBM-MSCs), a gold standard model of in vitro chondrogenesis (hBM-MSC-derived cartilage organoids), and an attractive in vivo target phenotype for clinically useful engineered cartilage (neonatal articular cartilage). These analyses highlighted a specific set of microRNAs involved in the chondrogenic program that could be manipulated to acquire a more robust articular cartilage-like phenotype. This characterization provides researchers in the cartilage tissue engineering field a useful atlas with which to contextualize microRNA involvement in complex differentiation pathways.

Project description:IntroductionKnee osteoarthritis (OA) is characterized by pain and functional deficits. Common conservative strategies include medications, physical therapy, and intra-articular injections. Recently, treatment using autologous cell injections has increased.ObjectiveTo characterize the cellular content of bone marrow aspirate (BMA) and to evaluate the effect of intra-articular autologous BMA injections in patients with mild knee OA.DesignProspective pilot observational study.SettingAcademic institution.PatientsEleven patients with unilateral or bilateral mild knee OA (15 knees) were included in the cellular analysis. Ten patients (13 knees) were included in the overall (cellular and clinical) analysis.InterventionsBMA was aspirated from patients' iliac crests and then injected intra-articularly under fluoroscopic and/or ultrasound guidance. BMA samples were analyzed using flow cytometry, colony forming unit (CFU) assays, and enzyme-linked immunosorbent assays. Questionnaires assessing pain and function were administered preinjection and at 1, 3, 6, and 12 months postinjection. Side effects and satisfaction were assessed.Main outcome measuresTotal nucleated cell (TNC) concentration, mesenchymal stem cell (MSC) concentration, CFU count, and interleukin-1 receptor antagonist (IL-1Ra) concentration.ResultsBMA sample analyses revealed wide ranges in TNC concentration (173300-4 491 050 cells/mL), MSC concentration (0-500 cells/mL), CFUs (0-19), and IL-1Ra concentration (2806-29 394 pg/mL). Improvements in Knee Injury and Osteoarthritis Outcomes Score for Joint Replacement were observed throughout the 12-month follow-up period (F[4,12] = 12.29, P < .001). Additionally, current, usual, best, and worst numerical rating scale pain scores significantly decreased over time (P < .001). Patient satisfaction was high (range: 8.1 ± 2.1-8.8 ± 1.9), and side effects were uncommon.ConclusionsThe cellular content of BMA samples varied widely between patients and was lower than the anticipated yield reported by the device's manufacturer. However, intra-articular BMA injections for knee OA in a small pilot cohort appeared to be safe with potential therapeutic value. Larger, prospective, double-blinded studies are warranted.

Dataset Information

Autologous bone marrow mesenchymal cell induced chondrogenesis for the treatment of osteoarthritis of knee.

Electronic supplementary material

Publications

Autologous bone marrow mesenchymal cell induced chondrogenesis for the treatment of osteoarthritis of knee.

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