“…Such challenges include (i) the need for intercellular communication and spatiotemporal coordination within three‐dimensional tissue‐engineered constructs [38, 39]; (ii) the limited proliferative capability and plasticity of adult stem cells and the need to achieve adequate cell numbers for therapeutic applications through extensive in vitro expansion [40, 41]; (iii) the nonspecific pleiotropic effects of cytokines, extracellular matrix (ECM) molecules and growth factors on lineage fate determination and cellular differentiation [42]; and finally (iv) the safety issues associated with the genetic modification of human stem cells and the use of viral vectors and recombinant DNA [43]. These clinical challenges have also been critically examined in detail elsewhere [37].…”