MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment.

The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration. The research was performed on the PubMed database considering the English literature from 2002 and using the following key words: cartilage, cartilage repair, mesenchymal stem cells, MSCs, bone marrow concentrate (BMC), bone marrow-derived mesenchymal stem cells, bone marrow stromal cells, adipose-derived mesenchymal stem cells, and synovial-derived mesenchymal stem cells. The systematic research showed an increasing number of published studies on this topic over time and identified 72 preclinical papers and 18 clinical trials. Among the 18 clinical trials identified focusing on cartilage regeneration, none were randomized, five were comparative, six were case series, and seven were case reports; two concerned the use of adipose-derived MSCs, five the use of BMC, and 11 the use of bone marrow-derived MSCs, with preliminary interesting findings ranging from focal chondral defects to articular osteoarthritis degeneration. Despite the growing interest in this biological approach for cartilage regeneration, knowledge on this topic is still preliminary, as shown by the prevalence of preclinical studies and the presence of low-quality clinical studies. Many aspects have to be optimized, and randomized controlled trials are needed to support the potential of this biological treatment for cartilage repair and to evaluate advantages and disadvantages with respect to the available treatments. IV.

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

Background:Bone marrow aspirate concentrate (BMAC) has emerged as a novel treatment for pathology of the knee. Despite containing a limited number of stem cells, BMAC serves as a source of growth factors that are thought to play an important role as a result of their anabolic and anti-inflammatory effects. To our knowledge, there is no systematic review regarding the outcomes of bone marrow aspirate concentrate used for the treatment of chondral defects and osteoarthritis of the knee.Purpose:To perform a systematic review on the outcomes of bone marrow aspirate concentrate for the treatment of chondral defects and osteoarthritis of the knee.Study Design:Systematic review; Level of evidence, 4.Methods:A systematic review of the literature was performed using the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed, and MEDLINE from 1980 to present. Inclusion criteria were as follows: use of BMAC for treatment of chondral defects and osteoarthritis of the knee,...

https://journals.sagepub.com/doi/pdf/10.1177/2325967115625481

Concentrated Bone Marrow Aspirate for the Treatment of Chondral Injuries and Osteoarthritis of the Knee: A Systematic Review of Outcomes

Background:Chondral lesions in athletically active patients cause considerable morbidity, and treatment with existing cell-based therapies can be challenging. Bone marrow has been shown as a possible source of multipotent stem cells (MSCs) with chondrogenic potential and is easy to harvest during the same surgical procedure.Purpose:To investigate the clinical outcome in a group of active patients with large full-thickness chondral defects of the knee treated with 1-step surgery using bone marrow–derived MSCs and a second-generation matrix.Study Design:Case series; Level of evidence, 4.Methods:From January 2007 to February 2010, 25 patients (average age, 46.5 years) with symptomatic large chondral defects of the knee (International Cartilage Repair Society grade 4) who underwent cartilage transplantation with MSCs and a collagen type I/III matrix were followed up for a minimum of 3 years. The average lesion size was 8.3 cm2. Coexisting injuries were treated during the same surgical procedure in 18 patients...

One-Step Surgery With Multipotent Stem Cells for the Treatment of Large Full-Thickness Chondral Defects of the Knee

Articular cartilage has a limited capacity to repair following injury. Early intervention is required to prevent progression of focal traumatic chondral and osteochondral defects to advanced cartilage degeneration and osteoarthritis. Novel cell-based tissue engineering techniques have been proposed with the goal of resurfacing defects with bioengineered tissue that recapitulates the properties of hyaline cartilage and integrates into native tissue. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy given the high proliferative capacity of MSCs and their potential to differentiate into cartilage-producing cells - chondrocytes. MSCs are historically harvested through bone marrow aspiration, which does not require invasive surgical intervention or cartilage extraction from other sites as required by other cell-based strategies. Biomaterial matrices are commonly used in conjunction with MSCs to aid cell delivery and support chondrogenic differentiation, functional extracellular matrix formation and three-dimensional tissue development. A number of specific transplantation protocols have successfully resurfaced articular cartilage in animals and humans to date. In the clinical literature, MSC-seeded scaffolds have filled a majority of defects with integrated hyaline-like cartilage repair tissue based on arthroscopic, histologic and imaging assessment. Positive functional outcomes have been reported at 12 to 48 months post-implantation, but future work is required to assess long-term outcomes with respect to other treatment modalities. Despite relatively positive outcomes, further investigation is required to establish a consensus on techniques for treatment of chondral and osteochondral defects with respect to cell source, isolation and expansion, implantation density, in vitro precultivation, and scaffold composition. This will allow for further optimization of MSC proliferation, chondrogenic differentiation, bioengineered cartilage integration, and clinical outcome.

/pdf/mesenchymal-stem-cells-in-the-treatment-of-traumatic-41l9sdvwfu.pdf

Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review.

Objective:The purpose of our study was to determine the effectiveness of cartilage repair utilizing 1-step surgery with bone marrow aspirate concentrate (BMAC) and a collagen I/III matrix (Chondro-...

/pdf/one-step-cartilage-repair-with-bone-marrow-aspirate-bx2vqqb0r6.pdf

One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions Results at 2-Year Follow-up

Laura Mazzucco

Papers

One-Step Cartilage Repair with Bone Marrow Aspirate Concentrated Cells and Collagen Matrix in Full-Thickness Knee Cartilage Lesions Results at 2-Year Follow-up