Enhancement of acellular cartilage matrix scaffold by Wharton's jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration

Abstract

Articular cartilage defect repair is a problem that has long plagued clinicians. Although mesenchymal stem cells (MSCs) have the potential to regenerate articular cartilage, they also have many limitations. Recent studies have found that MSC-derived exosomes (MSC-Exos) play an important role in tissue regeneration. The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix (ACECM) scaffold and to explore the underlying mechanism. The results of in vitro experiments show that human umbilical cord Wharton's jelly MSC-Exos (hWJMSC-Exos) can promote the migration and proliferation of bone marrow-derived MSCs (BMSCs) and the proliferation of chondrocytes. We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype. The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model. This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response, which may be a promoting factor for osteochondral regeneration. In addition, microRNA (miRNA) sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage. We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis. In summary, this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.

A Comprehensive Review on the Applications of Exosomes and Liposomes in Regenerative Medicine and Tissue Engineering

“…Using a rat knee joint osteochondral defect model, researchers discovered that hWJMSC-Exos could control the anterior cavity’s microenvironment. Furthermore, microRNA (miRNA) sequencing revealed that hWJMSC-Exos contains a large number of miRNAs that facilitate the regeneration of hyaline cartilage [ 146 ]. A recent study found that by combining stem cell-derived exosomes into tissue adhesive hydrogels, they could create something similar to a situ-shaped hydrogel matrix as a tissue patch for the sensitive EHG for cartilage fracture reconstruction.…”

“…Using a rat knee joint osteochondral defect model, researchers discovered that hWJMSC-Exos could control the anterior cavity's microenvironment. Furthermore, microRNA (miRNA) sequencing revealed that hWJMSC-Exos contains a large number of miRNAs that facilitate the regeneration of hyaline cartilage [146]. A recent study found that by combining stem cell-derived…”

Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases

“…Compared to BM-MSCs and ESC-MSCs, UC-MSCs have the advantages of painless collection procedure and non-ethical controversy (Ding et al, 2015 ). Jiang et al reported the regulatory function of the exosomes from human umbilical cord Wharton's jelly MSCs (hWJMSC-Exos) in a joint microenvironment via a rat model of cartilage defect, and further attributed this function to the inhibition of inflammatory response by promoting the polarization of macrophages toward M2 phenotype (Jiang et al, 2021 ). In addition, Yan et al ( Figure 5B ) found that the exosomes from UC MSCs (UC-MSCs-Exos) could promote chondrocyte proliferation, migration, and matrix synthesis; and inhibit apoptosis, which was correlated to the activation of TGF-β1 and Smad2/3 signaling (Yan and Wu, 2020 ).…”

Perspective: Challenges Presented for Regeneration of Heterogeneous Musculoskeletal Tissues that Normally Develop in Unique Biomechanical Environments

“…Thus, in this circumstance, the MSC do not appear to be immunologically rejected by the host. Because of this apparent immunological privilege, the use of human MSC such as those derived from Wharton’s jelly and other sources have been investigated (for example: Jiang et al, 2021 ).…”

“…In addition, while the TEC approach discussed above has been successful in the treatment of smaller cartilage defects, in many instances, a more extensive injury to meniscus, cartilage or a ligament or tendon may require a different approach, that of using scaffolds to augment implantation into the defects. Thus, incorporation of MSC into scaffolds have been investigated using scaffolds such as decellularized cartilage ( Jiang et al, 2021 ), collagen ( Sadlik et al, 2017 ), silk proteins ( Barlian et al, 2020 ), or scaffolds made of chemical polymers ( Liu et al, 2018 ). Such scaffolds may be biodegradable in vivo , but should have mechanical properties that allow for a sufficient time for the seeded cells to respond to the in vivo environment.…”