Synovial Fluid-Derived Mesenchymal Stem Cells (SF-MSCs)-Targeted Exosome Modification Service

Synovial fluid-derived mesenchymal stem cells (SF-MSCs) are considered to be an available cell treatment for cartilage degenerative lesions in osteoarthritis with applications in cartilage tissue engineering. Exosomes engineered to display targeting peptides on their surface can be used as carriers of regulatory molecules for precise targeting and control of SF-MSCs directed differentiation. Creative Biolabs offers clients flexible engineered exosome modification services for targeting SF-MSCs to advance SF-MSCs research projects based on exosomes.

Overview of SF-MSCs and Their Target-Regulated Directed Differentiation

With the potential to differentiate into osteoblasts, chondroblasts, adipocytes, and myoblasts, MSCs play a key role in replacing lost cells and repairing damaged tissues. Synovial fluid secreted by cells of the synovial lamina propria of bursae and tendon sheaths lubricates articular cartilage as well as provides cartilage nutrition, where MSCs with differentiation potential are found.

Retaining their cartilage differentiation and paracrine potential, SF-MSCs are an important source of chondrocytes for cartilage repair. SF-MSCs can be easily obtained by minimally invasive arthrocentesis, of which their potential for growth in vitro is also robust. Thus, SF-MSCs are considered as an available cell therapy for application in cartilage tissue engineering in osteoarthritis. However, similar to the pleiotropic potential of other MSCs, the differentiation of SF-MSCs is also pleiotropic. Possible access to improve the treatment of the strategy in cartilage tissue repair is suggested by controlling the differentiation of SF-MSCs to chondrocytes through the delivery of regulatory molecules. Remarkably, it is crucial to require a delivery system to control the precise delivery and release in targeted SF-MSCs.

Fig.1 The cell layers of the synovial membrane. (Fang, 2021)

Exosome Modifications Targeting the SF-MSCs at Creative Biolabs

With high biocompatibility and encapsulation stability due to their natural membrane structure, exosomes are ideal platforms for the precise delivery of drugs and molecules to guest regions with little risk of tumorigenesis. However, the delivery of natural exosomes to various cell types and tissues is non-selective, limiting their bioavailability and effective enrichment at focal sites. Creative Biolabs offers strategies to modify exosomal surface protein fractions to achieve specific targeting to SF-MSCs, thus circumventing negative delivery effects such as their being metabolized and stoichiometry. Specifically, an E7 peptide (EPLQLKM) with proven potential for targeting SF-MSCs was screened using phage-based display technology and linked to exosomal membrane proteins such as Lamp2b, thus completing the modification of exosomes capable of targeting SF-MSCs. This modification can be achieved not only by direct sexual attachment to exosomal membrane proteins, but also by constructing cell lines transfected with Lamp2b-E7 fusion plasmids to obtain engineered exosomes. Furthermore, this E7-modified engineered exosome modification strategy has been shown to adequately improve the targeting superiority of exosome vectors in both cellular and rat models of bone disease.

Fig.2 Schematic illustration on exosome engineering for enhanced delivery of KGN to SF-MSCs, and the co-injection of E7-Exo/KGN and SF-MSCs for cartilage regeneration and OA treatment. (Xu, 2021)

We provide construction services for specified cell lines containing E7 fusion plasmids to ensure stable expression of E7 peptides during exosome production. The collected cell supernatant of the engineered exosomes can then be scaled up and purified in our exosome production platform, leading to a high yield of E7-modified exosomes. Utilizing our exosome cargo delivery platform enables cargo loading into E7-modified exosomes, including modulating drugs and molecules. This E7-modified engineered exosome modification strategy has been shown to sufficiently improve the targeting superiority of exosome carriers in cellular and rat models of bone disease, which is investigated by functional assays to detect changes in SF-MSCs after exosome administration.

Creative Biolabs provides exosome modification strategies based on the modification of surface protein fractions to achieve specific targeting to SF-MSCs, facilitating the application of SF-MSCs in the treatment of bone-related disorders. Our talented team is pleased to provide high-quality customized research services to meet your needs. Please feel free to contact us to create a custom quote.

References

Fang, W.; et al. Synovial fluid mesenchymal stem cells for knee arthritis and cartilage defects: a review of the literature. J Knee Surg. 2021, 34(13): 1476-1485.
Xu, X. et al. Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration. Biomaterials. 2021, 269: 120539.

Plant Exosome Isolation