Are adipose-derived stem cells cultivated in human platelet lysate suitable for heart valve tissue engineering?

Abstract

Tissue-engineered heart valves represent a promising strategy for the growing need for valve replacements in cardiovascular medicine. Recent studies have shown that adipose-derived stem cells (ADSC) are a viable cell source, as they are readily available in both the young and the elderly, show diverse differentiation potential and adapt their extracellular matrix (ECM) to a varying mechanical load. In vitro culture medium is usually enriched with fetal calf serum (FCS). However, a promising substitute has recently been found in human platelet lysate (HPL), which is superior in terms of proliferation speed and allogenicity. This study sought to elucidate the suitability of ADSC and HPL for heart valve tissue engineering (TE). ADSC harvested from five healthy individuals were cultured in both FCS and HPL. The cells were observed for differentiation potential, proliferation speed and immunophenotype, using immunohistochemistry and FACS analysis. Neotissue was assessed for ECM composition, human collagen I (hColl1) formation, histomorphology and mechanical stiffness under uniaxial tensile stress. Neotissue cultured in HPL was found to be significantly inferior in mechanical rigidity; it showed a three-fold higher proliferation rate and a more dense ECM, but also a more heterogeneous hColl1 distribution. ECM analysis showed significantly higher amounts of DNA and glycosaminoglycans (GAG) in HPL-cultured tissue. No significant differences were observed for differentiation potential and immunophenotype, apart from a lower CD166 expression in HPL. The mechanical inferiority of neotissue cultured in HPL represents a limitation to the use of HPL-enriched media for heart valve TE with ADSC. This result concurs with data published about HPL and myofibroblasts derived from the venous wall. Similarly, the mechanical inferiority is not rooted in a difference in ECM composition, but rather in hColl1 architecture. Stem cell properties, as documented in the literature, are retained with HPL. A possible connection between the mechanical inferiority and the observed decrease in CD166 needs further investigation. Copyright © 2016 John Wiley & Sons, Ltd.