Attenuation of osteoarthritis progression through intra-articular injection of a combination of synovial membrane-derived MSCs (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome)

Abstract

Purpose Osteoarthritis (OA) as a progressive destructive disease of articular cartilage is the most common joint disease characterized by reduction of joint cartilage thickness, demolition of cartilage surface and new bone formation. To overcome these problems, the purpose of the current research was to evaluate and compare the in vivo effects of synovial membrane-derived mesenchymal stem cell (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome) on collagenase II-induced rat knee osteoarthritis (KOA) remedy. Methods For the first step, SMMSCs were isolated and characterized. Also, secretome was collected from SMMSCs culture. Furthermore, PRP was collect from the rat heart venous blood. Second, two injection of collagenase II with an interval of 3 days was performed in the knee intra-articular space to induce osteoarthritis. Two weeks later, animals were randomly divided into 6 groups. Control group without treatment, positive group: taken an intra-articular sodium hyaluronate injection (0.1 ml), treatment groups taken an intra-articular injection of; treatment 1: SMMSCs (5 × 106), treatment 2: SMMSCs (5 × 106)/secretome (50 µl), treatment 3: SMMSCs (5 × 106)/PRP (50 µl), and treatment 4: SMMSCs (5 × 106)/ secretome (50 µl)/ PRP (50 µl). Three months later, rats were killed and the following assessments were executed: radiography, histopathology, and immunohistochemistry. Results Our findings represented that a combination of the SMMSCs/secretome/PRP had a considerable effect on glycosaminoglycans (GAGs) and collagen II contents, articular cartilage preservation, compared with other groups. In addition, combination of the SMMSCs with PRP and secretome showed the lowest expression of mmp3, while SOX9 had the highest expression in comparison with other groups. Also, SMMSCs-injected groups demonstrated better results compared with positive and control groups. Conclusions Injecting a combination of the SMMSCs/secretome/PRP resulted in better efficacy in terms of joint space width, articular cartilage surface continuity and integrity, sub-chondral bone and ECM constituents such as collagen II. Indeed, transplantation of this combination could be considered as a preliminary therapy for clinical trial study in the future.

A first report on the efficacy of a single intra-articular administration of blood cell secretome, triamcinolone acetonide, and the combination of both in dogs with osteoarthritis

“…Still, a growing body of evidence indicates that other peripheral blood cells can release biologically active paracrine factors that can produce regenerative effects [52], specifically in joint cartilage [53,54]. In a rat model, the addition of conditioned medium secretome from mesenchymal stem cells leads to lower levels of inflammatory factors and better results than a control group [55]. Although many of the animals included in the sample already had severe OA and still showed improvements, there is a case to be made for earlier use of BCS, as its effects are produced through the interaction with the different types of joint cells and tissues, so they may need to be present in enough number for a more significative response to be observed and to preserve healthy tissues [28].…”

Platelet Rich Plasma in the Repair of Articular Cartilage Injury: A Narrative Review

“…At the same time, it can induce synovial mesenchymal stem cells to differentiate into chondrocytes, increase the generation of cartilage markers, and then improve joint function. 87 , 88 Whether PRP injected into human joints can play the same role needs further clinical experimental research.…”

The Nrf2/HO‐1 pathway participates in the antiapoptotic and anti‐inflammatory effects of platelet‐rich plasma in the treatment of osteoarthritis

“…Forty‐two SD rats (Vital River Biotech) were randomly classified into seven groups ( n = 6/group)as follows: control group, OA group (OA rats injected with 50 μL of normal saline), OA + PRP group (OA rats injected with 50 μL of PRP), OA + PRP + Vehicle group (OA rats injected with 50 μL of PRP and orally administered vehicle daily), OA + PRP + brusatol (OA rats injected with 50 μL of PRP and orally administered brusatol daily), OA + PRP + LV‐shNC (OA rats injected with 50 μL of PRP, then infected with LV‐shRNA‐NC particles for 60 h, and finally injected with 50 μL of PRP 22,23 ), and OA + PRP + LV‐shNrf2 group (OA rats injected with 50 μL of PRP, then infected with LV‐shRNA‐Nrf2 particles for 60 h, and finally injected with 50 μL of PRP). OA was induced through anterior cruciate ligament transection (ACLT), as previously described 24,25 .…”