Methods of Modification of Mesenchymal Stem Cells and Conditions of Their Culturing for Hyaline Cartilage Tissue Engineering

Abstract

The use of mesenchymal stromal cells (MSCs) for tissue engineering of hyaline cartilage is a topical area of regenerative medicine that has already entered clinical practice. The key stage of this procedure is to create conditions for chondrogenic differentiation of MSCs, increase the synthesis of hyaline cartilage extracellular matrix proteins by these cells and activate their proliferation. The first such works consisted in the indirect modification of cells, namely, in changing the conditions in which they are located, including microfracturing of the subchondral bone and the use of 3D biodegradable scaffolds. The most effective methods for modifying the cell culture of MSCs are protein and physical, which have already been partially introduced into clinical practice. Genetic methods for modifying MSCs, despite their effectiveness, have significant limitations. Techniques have not yet been developed that allow studying the effectiveness of their application even in limited groups of patients. The use of MSC modification methods allows precise regulation of cell culture proliferation, and in combination with the use of a 3D biodegradable scaffold, it allows obtaining a hyaline-like regenerate in the damaged area. This review is devoted to the consideration and comparison of various methods used to modify the cell culture of MSCs for their use in regenerative medicine of cartilage tissue.

Perlecan, A Multi-Functional, Cell-Instructive, Matrix-Stabilizing Proteoglycan With Roles in Tissue Development Has Relevance to Connective Tissue Repair and Regeneration

“…Perlecan domain I BMP-2 hydrogels have also been shown to promote chondrogenesis and cartilage repair in a murine early OA model (Yang et al, 2006;Jha et al, 2009;Srinivasan et al, 2012). BMP-2 and BMP-9 can also promote chondrogenic differentiation of human multipotential mesenchymal stem cells (Majumdar et al, 2001;Shestovskaya et al, 2021). Perlecan domain I collagen I fibril scaffolds have been used as an FGF-2 delivery system that could also be useful in cartilage repair strategies (Yang et al, 2005).…”

Cartilage-Specific Gene Expression and Extracellular Matrix Deposition in the Course of Mesenchymal Stromal Cell Chondrogenic Differentiation in 3D Spheroid Culture

“…The generation of hyaline cartilage by MSCs requires combining the following key elements: creating conditions for the chondrogenic differentiation of MSCs, prompting the cells to increase the synthesis of hyaline cartilage ECM proteins, and activating cell proliferation. Various techniques were tested to achieve this goal, including the addition of protein factors (TGF-β superfamily members, bone morphogenetic proteins, insulin-like growth factor-I, fibroblast growth factor, proteoglycans), the formation of 3D structures by using scaffold-free or scaffold-based technologies, and the application of various physical agents (mechanical impact, hypoxia, electromagnetic radiation (photobiomodulation)) [ 18 , 19 , 20 ]. The selection of the optimal type of MSC with the highest chondrogenic capacity was the aim of the present study.…”

Surface Acoustic Wave (SAW)‐Based Sonoporation of Single‐Adherent‐Cell

“…Advances in cell therapies, such as Chimeric antigen receptor T (CART)-cell immunotherapy [1,2] and regenerative therapy, [3] have recently led to outstanding clinical successes. Developing such cell-therapy products requires one necessary process called transfection, which performs intracellular delivery of nucleic acids and proteins to edit genes of the target cell.…”