Stem Cell-Based Therapy and Cell-Free Therapy as an Alternative Approach for Cardiac Regeneration.

The World Health Organization reports that cardiovascular diseases (CVDs) represent 32% of all global deaths. The ineffectiveness of conventional therapies in CVDs encourages the development of novel, minimally invasive therapeutic strategies for the healing and regeneration of damaged tissue. The self-renewal capacity, multilineage differentiation, lack of immunogenicity, and immunosuppressive properties of mesenchymal stem cells (MSCs) make them a promising option for CVDs. However, growing evidence suggests that myocardial regeneration occurs through paracrine factors and extracellular vesicle (EV) secretion, rather than through differentiation into cardiomyocytes. Research shows that stem cells secrete or surface-shed into their culture media various cytokines, chemokines, growth factors, anti-inflammatory factors, and EVs, which constitute an MSC-conditioned medium (MSC-CM) or the secretome. The use of MSC-CM enhances cardiac repair through resident heart cell differentiation, proliferation, scar mass reduction, a decrease in infarct wall thickness, and cardiac function improvement comparable to MSCs without their side effects. This review highlights the limitations and benefits of therapies based on stem cells and their secretome as an innovative treatment of CVDs.

Utility of direct 3D co-culture model for chondrogenic differentiation of mesenchymal stem cells on hyaluronan scaffold (Hyaff-11).

This study presents direct 2D and 3D co-culture model of mesenchymal stem cells (MSCs) line with chondrocytes isolated from patients with osteoarthritis (unaffected area). MSCs differentiation into chondrocytes after 14, 17 days was checked by estimation of collagen I, II, X, aggrecan expression using immunohistochemistry. Visualization, localization of cells on Hyaff-11 was performed using enzymatic technique and THUNDER Imaging Systems. Results showed, that MSCs/chondrocytes 3D co-culture induced suitable conditions for chondrocytes grow and MSCs differentiation than 2D monoculture. Despite that differentiated cells on Hyaff-11 expressed collagen X, they showed high collagen II (80%) and aggrecan (60%) expression with simultaneous decrease of collagen I expression (10%). The high concentration of differentiated cells on Hyaff-11, indicate that this structure has an impact on cells cooperation and communication. In conclusion, we suggest that high expression of collagen II and aggrecan in 3D co-culture model, indicate that cooperation between different subpopulations may have synergistic impact on MSCs chondrogenic potential. Revealed the high concentration and localization of cells growing in deeper layers of membrane in 3D co-culture, indicate that induced microenvironmental enhance cell migration within scaffold. Additionally, we suggest that co-culture model might be useful for construction a bioactive structure for cartilage tissue regeneration.