iPS Differentiation to smooth muscle cells

Stem cells are a valuable cell source for tissue engineering due to their high proliferative and differentiation capabilities. We have developed techniques for the differentiation of adult stem cells (mesenchymal cells) as well as hES and hiPS cells into SMCs. In general, we utilize a combination of cell adhesion substrates, mechanical stretching as well as growth factor addition to induce differentiation towards SMC phenotype.

More recently, we have been successful in engineering vessel grafts using hiPS cells. Cells were first differentiated into mesenchymal cells via a neural crest intermediate. Mesenchymal cells were then utilized in the bioreactor over 8 weeks under pulsatile conditions and various growth factor scheduling (TGFb, PDGF, bFGF) to grow vessel grafts. Vessel grafts engineered using hiPS cells exhibited a burst pressure of approximately 700 mm Hg, stained positive for SMA (early), SM22 (mid) and calponin (mid) positive cells (by PCR, immunostaining, Western Blot). The vessel wall stained positive for collagen I, collagen III, fibronectin and GAGs. Additionally, we confirmed that the vessel walls were negative for adipogenic, chondrogenic and osteocytic lineages.

Relevant publications:

1. Sundaram S, One J, Siewert J, Teodosescu S, Zhao L, Dimitrievska S, et al. Tissue-engineered vascular grafts created from human induced pluripotent stem cells. Stem Cells Transl Med. 3(12), 1535, 2014.

2. Sundaram S, Echter A, Sivarapatna A, Qiu C, Niklason L. Small diameter vascular graft engineered using human embryonic stem cell-derived mesenchymal cells. Tissue Eng Part A. 2013.

3. Sundaram S, Niklason LE. Smooth muscle and other cell sources for human blood vessel engineering. Cells Tissues Organs (Print). 195(1-2), 15, 2012.

4. Gong Z, Niklason LE. Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs). FASEB J. 22(6), 1635, 2008.