Berberine Encapsulated in Exosomes Derived from Platelet-Rich Plasma Promotes Chondrogenic Differentiation of the Bone Marrow Mesenchymal Stem Cells <i>via</i> the Wnt/β-Catenin Pathway

Abstract

Cartilage regenerative medicine, wherein the stem cells from adults exert a crucial role, has high potential in the treatment of defective articular cartilage. Recently, Bone marrow mesenchymal stem cells (BMSCs) are being increasingly recognized as an alternative source of adult stem cells, which are capable of differentiating into several cell types (e.g., adipocytes, chondrocytes, and osteoblasts). However, their proliferative properties and tendency to dedifferentiate restrict their use in clinical settings. Recently, a possible bioactive material PRP-exos (exosomes derived from platelet-rich plasma), has emerged, which can effectively facilitate the differentiation and proliferation of cells. Recent studies have reported that berberine (Ber), known to have antiinflammatory properties, plays a role in osteogenesis. Since biological molecules are used in combinations, we attempted to assess the effect of Exos-Ber (PRP-exos in combination with Ber) on the chondrogenic differentiation of BMSCs in vitro. In this study, Exos-Ber was observed to promote the proliferation of BMSCs and cause their chondrogenic differentiation in vitro. Additionally, Exos-Ber could promote the migration of BMSCs and increase the protein expression of the chondrogenic genes (Collagen II, SOX9, Aggrecan). After treatment with Exos-Ber, significant induction of β-catenin expression was observed, which could be repressed successfully by adding β-catenin inhibitor XAV-939. Interestingly, the repression of the Wnt/β-catenin axis also resulted in reduced gene expression levels of Collagen II, SOX9, and Aggrecan.These observations indicated that Exos-Ber facilitated the differentiation of chondrogenic BMSCs by modulating the Wnt/β-catenin axis, which offers innovative insights into the reconstruction of cartilage.

Advances in Platelet Rich Plasma-Derived Extracellular Vesicles for Regenerative Medicine: A Systematic-Narrative Review

“…According to all reported works compiled in this review, PRP-EVs represent a promising therapeutic approach in the field of tissue repair and regeneration. PRP-EVs promoted cell proliferation and migration [31,34,35,[40][41][42][45][46][47][48][49][50] and angiogenesis [35,45,50] while reducing the inflammatory response [31][32][33]41,42], apoptosis [31,34,41,42,50] the oxidative stress [41] and senescence [41], among others. PRP-EVs seem to exert their function through different signaling pathways such as Wnt/β-catenin [31,47,50], AKT/ERK [35,45], TLR4 [39], PI3K/Akt [40], PGC1α-TFAM [41], Keap1-Nrf2 [42], YAP [45] and Akt/Bad/Bcl-2 [50].…”

The effect of ovarian injection of autologous platelet rich plasma in patients with poor ovarian responder: a systematic review and meta-analysis

“…Studies in various fields have found that PRP can promote cell proliferation and migration ( 61 , 62 ), angiogenesis ( 63 , 64 ), and reduce inflammatory reactions, oxidative stress, and aging ( 65 , 66 ). In addition, research has found that PRP appears to function through different signaling pathways, such as AKT/ERK ( 63 , 64 ), PGC1 α- TFAM ( 65 ), Keap1-Nrf2 ( 66 ), Wnt/β- Chain proteins ( 67 ), TLR4 ( 68 ), PI3K/Akt ( 69 ), and Akt/Band/Bcl-2 ( 70 ). However, there is still a lack of research on the pathways involved in PRP promoting ovarian regeneration and improving POR, and further research is needed to elucidate its related mechanisms.…”

Preparation of genetically or chemically engineered exosomes and their therapeutic effects in bone regeneration and anti-inflammation

“…The frequent physical methods include: co-incubation, electroporation, sonication, mechanical extrusion, etc (Figure 4A) (Haney et al, 2015). All of these methods can deliver cargos to exosomes such as miRNA, siRNA, proteins, lipophilic drugs like curcumin (Cur) (Lin et al, 2018;Guo et al, 2019;Pomatto et al, 2019;He et al, 2020;Wang et al, 2021), and water-soluble drugs like berberine (Table 2) (Dong et al, 2022). Therapeutic miRNA and proteins are usually loaded into exosomes using endogenous loading methods, while small molecule cargos are mainly loaded using exogenous loading methods, sometimes endogenous and exogenous methods can be combined to produce engineering exosomes.…”