Table 1:

Advantages and challenges of multi-cell lineage model systems using hiPSC-derivative cell types

Multi-lineage platform	Advantages	Challenges
2D co-culture	Highly scalable and amenable to rapid interrogation of cellular, transcriptional, genetic, and signaling mechanisms	Unable to match the 3D physiological complexity associated with other in-vitro systems
In-silico	Large computational power enables highly scalable predictive modeling of biological processes and drug responses.	Non-biological platform and dependent on input from accurate biological datasets to establish a useful predictive model
Microfluidic organ and body chips	More accurate mimic of in vivo physiological forces than traditional 2D cell culture. Integrates the concept of systemic vasculature through microfluidic channels. Simultaneous interrogation of multiple cell types in a fully-integrated system.	Modest scalability, expensive, and necessary to find appropriate biocompatible materials for cell culture
Tissue engineering and 3D printing	Three-dimensionality enables more realistic mimicking of in vivo tissues with potential functional uses for human transplantation	Less scalable than traditional monoculture and cost of bioprinting and bioengineering platforms can be a limiting factor. Biocompatible bioinks must be further refined.
Organoids and assembloids	More realistically mimic in vivo developmental processes in an in vitro setting while retaining moderate scalability	Maximum size is limited without adequate vascularization. Potential for tissue necrosis within organoid interior.
Humanized animals and chimeras	A physiologically relevant in vivo platform for studying development and potentially serving as a system for mass producing human tissues for transplantation purposes	Expensive and limited throughput. Significant bioethical concerns with growing human reproductive, neural, and other tissues in animals.