Professor of Biomedical Engineering Texas A & M University, United States
Introduction:: An intact and properly functioning lymphatic system is essential for the efficient return of excess interstitial fluid to the venous circulation. Injuries to the lymphatic system can result in lymphedema and other complicated conditions that may severely affect the patients’ quality of life. The injection of mesenchymal stem cell (MSC) suspension shows enhancement in lymphangiogenesis, but the effects are compromised due to limited cell retention and engraftment after transplantation. To address this, we have demonstrated the beneficial effects of MSC-secreted extracellular matrix (ECM) in augmenting lymphangiogenesis and cell regenerative activities.
Materials and Methods:: An in vitro co-culturing model of MSC sheets with lymphatic endothelial cells (LECs) was utilized to examine the effects of ECM in promoting lymphangiogenesis. A mouse tail lymphedema model, where rat MSC sheet fragments was injected, was used to investigate the role of MSC-secreted ECM in stimulating lymphangiogenesis. The anastomosis of the construct to the host tissue was evaluated by subcutaneously implanting the ECM-incorporated MSC-LEC construct in an athymic rat model.
Results, Conclusions, and Discussions:: Both the in vitro co-culturing of MSC sheets with LECs and the in vivo mouse tail lymphedema model confirmed that the MSC-secreted ECM significantly enhanced lymphangiogenesis compared to MSCs without ECM. The subcutaneous implantation of the ECM-incorporated MSC-LEC construct in the athymic rat model exhibited successful anastomosis of the construct to the host tissue, which is crucial for the application of MSC construct with engineered lymph vasculature in treating secondary lymphedema. Overall, our findings underscore the potential of MSC construct as a promising approach to improving therapeutic outcomes for the lymphatic system.
