Human pluripotent stem cells (hPSCs) are being used for the development of innovative advanced models of healthy and diseased human tissues, including neural, cardiac and hepatic tissues, by combining stem cell biology and engineering approaches, for further applications in disease modelling, drug screening, toxicology assays and regenerative medicine. Improved reprogramming techniques and innovative gene editing strategies are being used for the derivation of disease-specific human induced pluripotent stem cell (hiPSC) lines, and their isogenic controls, and consequences of epigenetic disfunction in hiPSC fate are being studied and monitored. Moreover, innovative genome editing strategies are being used for the derivation of hPSC with genetic compatibility with the patient for regenerative medicine applications. Molecular mechanisms that affect the maintenance of hiPSC pluripotency versus their differentiation into particular cell fates are being studied using novel biosystems engineering approaches. Knowledge collected is used for the creation of artificial niches for a more controlled hiPSC differentiation through the application of bioengineering strategies such as micropatterning, microfluidics and microencapsulation. Among other applications, these tools will be used to promote the vascularization of the hiPSC-based 3D tissue models. Manufacturing strategies based on the use of bioreactors are being developed for the large scale production of hiPSCs and their differentiated derivatives for the previously described in vitro applications as well as for regenerative medicine. An important focus is given to the development of xeno-free culture conditions and the use of disposable bioreactors.