F. Veronesi (Bologna, IT)Rizzoli Orthopedic Institute
Presenter Of 2 Presentations
18.2.8 - Modulation of the inflammatory osteoarthritis environment in presence of MSCs from bone marrow and adipose tissue: an in vitro study
Osteoarthritis (OA) is a degenerative and inflammatory joint disease, due to the high levels of pro-inflammatory cytokines and catabolic enzymes. The scarce regenerative capacity of cartilage and the limited outcome of the therapies are increasing the interest in mesenchymal stem cells (MSCs). Furthermore, in literature it is yet observed that platelet-rich plasma (PRP), thanks to its regenerative and anti-inflammatory abilities, is a recommended treatment for OA, as well as being a low-cost biological and not invasive remedy. This study investigates the chondrogenic ability of MSCs from adipose tissue (ADSCs) and bone marrow (BMSCs) in an OA-like microenvironment; evaluates the anti-inflammatory and regenerative roles of blood autologous protein solution (APS), enriched of anti-inflammatory cytokines and growth factors.
Methods and Materials
BMSC and ADSC micromasses, stimulated with interleukin (IL)1β and tumor necrosis factor (TNF)α or synovial fluid from OA patients, were cultured for 4 weeks in presence or absence of APS conditioned medium (CM). Their differentiation toward chondrogenic lineage was evaluated with histology, immunohistochemistry, histomorphometry and molecular biology approaches.
ADSCs and BMSCs were well organized in compact micromasses, with a more abundant matrix in ADSCs and cellularity in BMSCs (Figure 1). Gene expression of SOX9 and ACAN decreased in presence of inflammatory factors and did not recover with CM (in ADSC and BMSC). Conversely, the addition of CM reduced Metalloproteinases (MMP13), collagen (COL1a1), COLL X and COLL I in ADSCs and BMSCs. COL2a1 and MMP13 were respectively more and less expressed in ADSCs than in BMSCs in all culture conditions. Moreover, CM appeared to have more effect in cells treated with IL1β and TNFα than those treated with synovial fluid.
From these preliminary results it seems that both ADSCs and BMSCs might contribute to cartilage regeneration in a joint affected by OA and that APS might be useful in this regard.
23.4.6 - Amniotic epithelial stem cells (AECs) Vs adipose-derived mesenchymal stem cells (ADSCs): biological treatment for osteoarthritis
Osteoarthritis (OA) is the most common chronic degenerative joint disease, causing pain and decreased functionality. MSCs from adipose tissue (ADSCs) are attractive stem cell types thanks to their abundance, ease of harvest and high proliferation potential. ADSCs can be used as cell suspension (SVF) (one-step) or in vitro expanded (two-step). Preclinical studies yet showed the potential of expanded ADSCs in inhibiting OA progression. The amniotic epithelial stem cells (AECs) have regenerative properties similar to those of embryonic ones, are rapidly available, have not ethical concerns and don’t form tumor after transplantation. Currently, no authors evaluated AEC effects in cartilage diseases. This study aims to develop a new minimally invasive biological approach for OA treatment, comparing the therapeutic potential of AECs, ADSCs and SVF in the treatment of experimentally induced OA in sheep.
Methods and Materials
24 adult female sheep underwent to bilateral, lateral meniscectomy accordingly to Delling et al. The 48 knee joints randomly received an intra-articular injection of expanded allogenic AECs, autologous SVF, autologous expanded ADSCs or saline solution (control), 6 weeks after meniscectomy. After 3 and 6 months from the treatments, joints were evaluated with macroscopy, histology and histomorphometry.
From the preliminary macroscopic evaluations (Figure 1), it was shown that: 1) lateral compartment (red circles) was the most affected by OA; 2) the highest OA signs were observed in the control condyles, especially at 6 months; 3) the best infiltrative treatments were SVF or AEC injections; 4) worst results were obtained with culture expanded ADSCs.
Bilateral, lateral meniscectomy induces OA that gets worse over time. One injection of SVF or AECs, 6 weeks after OA induction, seems to improve the clinical picture, while 1 injection of culture expanded ADSCs doesn’t ameliorate OA signs. These preliminary results will be confirmed by histology and histomorphometry that are in progress.