Synergistic Effect of Inducible Factors on the Differentiation of Human Adipose-Derived Stem Cells to Vascular Cells

Author(s): Renu Ramesh, Jayakumar K, Lissy K Krishnan

The use of cells derived from the patient’s tissue is an attractive approach to develop autologous tissue-engineered vascular graft (TEVG) to bypass the diseased blood vessel. Multipotent human adipose-derived mesenchymal stem cells (hADMSCs) have the potential to differentiate into both smooth muscle cells (SMCs) and endothelial cells (ECs). However, the disease conditions affecting the growth and differentiation potential of cardiovascular disease (CVD) patient’s MSC (pADMSCs) is a hindrancee.

This study aimed to derive both endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs) from pADMSCs using a specific niche comprising fibrin and other inducers. pADMSCs were seeded on SMC-specific/EC-specific fibrin matrix coated on tissue culture polystyrene (TCPS) surface. In the third passage, pADMSCs were exposed to GFs for a specific period to induce pADMSCs to SMPCs. For inducing hADMSCs to EPCs, cells were exposed to GFs, followed by hypoxia. The EPCs were seeded in the lumen of a scaffold and applied shear stress to induce into ECs. The relative gene expressions at different stages were assessed by mRNA quantification and at the protein level by immunocytochemistry of final differentiated cells. A consistent matrix and GF dependent protocol facilitated derivation of SMPCs/SMCs with early, mid, and late markers. Sequential action by GF, hypoxia (HO), and shear stress (SS) differentiated pADMSCs to EPCs/ECS. The study established that patient-specific ECs and SMCs may be derived from ADMSCs for the construction of intimal and medial layers of TEVG aiming to fabricate autologous blood vessels.