Effect study of exosomes derived from platelet-rich plasma in the treatment of knee cartilage defects in rats

Abstract

Background The repair of articular cartilage defects has always been a difficult problem. We aimed to investigate the therapeutic effect of intra-articular injection of platelet-rich plasma (RPR) and PRP-derived exosomes (PRP-Exos) on cartilage defects in rat knee joints and then provide experience for the use of PRP-exos in cartilage defect repair. Methods Rat abdominal aortic blood was collected, and PRP was extracted by two-step centrifugation. PRP-exos were obtained by kit extraction, and PRP-exos were identified by various methods. After the rats were anesthetized, a cartilage defect subchondral bone was created at the proximal end of the origin of the femoral cruciate ligament with a drill. SD rats were divided into 4 groups, including PRP group, 50 μg/ml PRP-exos group, 5 μg/ml PRP-exos group, and control group. One week after the operation, 50 μg/ml PRP, 50 μg/ml PRP-exos, 5 μg/ml PRP-exos and normal saline were injected into the knee joint cavity of rats in each group, once a week. A total of two injections were given. On the 5th and 10th week after drug injection, the serum levels of matrix metalloproteinase 3 (MMP-3) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) were detected by each treatment method, respectively. The rats were killed at the 5th and 10th weeks, respectively, and the cartilage defect repair was observed and scored. The defect repair tissue sections were used for HE staining and type II collagen immunohistochemical staining. Results The histological results showed that both PRP-exos and PRP could promote cartilage defect repair and type II collagen formation, and the promoting effect of PRP-exos was significantly better than that of PRP. In addition, enzyme-linked immunosorbent assay (ELISA) results showed that compared with PRP, PRP-exos could significantly increase serum TIMP-1 and decrease serum MMP-3 in rats. And the promoting effect of PRP-exos was concentration dependent. Conclusion Intra-articular injection of PRP-exos and PRP can promote the repair of articular cartilage defects, and the therapeutic effect of PRP-exos is better than the same concentration of PRP. PRP-exos are expected to be an effective treatment for cartilage repair and regeneration.

In-situ gelation of fibrin gel encapsulating platelet-rich plasma-derived exosomes promotes rotator cuff healing

“…Their clinical application value is not only reflected in the coagulation function similar to PRP but PRP-Exos can also traverse various tissue barriers. Notably, they possess the ability to promote re-epithelialization and angiogenesis 18 – 21 and expedite the regeneration of bone and cartilage 22 , 23 . These findings underscore the substantial promise of PRP-Exos in the treatment of RCT.…”

3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius

“…Among the bioactive components, EVs have emerged as the most promising candidates for clinical application due to their exceptional bioactivity, stability, and highly feasible modular customized modifications [ 23 ]. Among these, exosomes, a representative type of small extracellular vesicles, are selective 30–150 nm vesicles that encapsulate proteins and nucleic acids, and have been increasingly utilized in tissue regeneration over the past few years [ 24 , 25 ]. High bioactivity serum exosomes, in particular, have been demonstrated as a composite that promotes bone regeneration, and their combination with degradable metal scaffolds not only facilitates rapid bone regeneration, but also addresses the issue of mechanical support deficiency at the bone defect site [ 26 , 27 ].…”

Thermo-Responsive Hyaluronan-Based Hydrogels Combined with Allogeneic Cytotherapeutics for the Treatment of Osteoarthritis

“…Injectable combination products may also be considered for potentially enhanced OA management, with the incorporation of an appropriate active pharmaceutical ingredient (API, e.g., Cingal, HA-triamcinolone hexacetonide, Anika Therapeutics) or a biological agent (e.g., cell therapies, cellular derivatives), in order to exert an additional pharmacological or complex effect [ 10 , 28 , 32 ]. Therein, multiple biological material sources (e.g., autologous platelet derivatives, allogeneic stem and progenitor cells, cell secretomes, exosomes) have been proposed or clinically applied for knee OA, yielding some encouraging results (e.g., OA symptom alleviation as measured by WOMAC pain scores) [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Specifically, significant positive evolution of arthralgia, cellular and humoral immune responses, and patient histological parameters were reported for combinations of autologous platelets and HA, for example [ 33 ].…”

“…Specifically, significant positive evolution of arthralgia, cellular and humoral immune responses, and patient histological parameters were reported for combinations of autologous platelets and HA, for example [ 33 ]. Currently, specific available insights into the pathophysiology of knee OA prompt the consideration and the further study of such injectable HA-based and biologically-based combination products for tentative enhanced management of the disease at its various stages [ 28 , 32 , 39 ]. Indeed, an optimal orthopedic therapeutic product could possibly comprise simple yet robust physical attributes (e.g., highly viscous gel in situ, adapted for local injection administration) supplemented with complex biological components (e.g., therapeutic cells or cell derivatives) providing ancillary or complementary effects [ 14 , 29 , 35 ].…”