Engineering cardiac tissue in vivo from human adipose-derived stem cells

Abstract

Cardiac tissue engineering offers promise as a surgical approach to cardiac repair, but requires an adequate source of cardiomyocytes. Here we evaluate the potential for generating human cardiac muscle cells in vivo from adipose-derived stem cells (ASC) by co-implanting in a vascularised tissue engineering chamber with inducing rat cardiomyocytes (rCM). Co-implantation (ASC-rCM) was compared with rCM or ASC controls alone after 6 weeks. Immunostaining using human nucleus specific antibody and cardiac markers revealed several fates for ASC in the chamber; (1) differentiation into cardiomyocytes and integration with co-implanted rCM; (2) differentiation into smooth muscle cells and recruitment into vascular structures; (3) adipogenic differentiation. ASC-rCM and ASC groups grew larger tissue constructs than rCM alone (212+/-25 microl, 171+/-16 microl vs. 137+/-15 microl). ASC-rCM and rCM groups contracted spontaneously at up to 140 bpm and generated a 10-15-fold larger volume of cardiac muscle (14.5+/-4.8 microl and 18.5+/-2.6 microl) than ASC alone group (1.3+/-0.5 microl). Vascular volume in ASC-rCM group was twice that of the rCM group (28.7+/-5.0 microl vs. 14.8+/-1.8 microl). The cardiac tissue engineered by co-implanting human ASC with neonatal rCM showed in vivo plasticity of ASC and their cardiomyogenic potential in tissue engineering. ASC contribution to vascularisation also promoted the growth of engineered tissue, confirming their utility in this setting.