Cell therapies have emerged as a promising therapeutic modality with the potential to treat and even cure a diverse array of diseases. Cell therapies offer unique clinical and therapeutic advantages over conventional small molecules and the growing number of biologics. Particularly, living cells can simultaneously and dynamically perform complex biological functions in ways that conventional drugs cannot; cell therapies have expanded the spectrum of available therapeutic options to include key cellular functions and processes. As such, cell therapies are currently one of the most investigated therapeutic modalities in both preclinical and clinical settings, with many products having been approved and many more under active clinical investigation. Here, we highlight the diversity and key advantages of cell therapies and discuss their current clinical advances. In particular, we review 28 globally approved cell therapy products and their clinical use. We also analyze >1700 current active clinical trials of cell therapies, with an emphasis on discussing their therapeutic applications. Finally, we critically discuss the major biological, manufacturing, and regulatory challenges associated with the clinical translation of cell therapies.

We have developed a dual-chambered bioreactor (DCB) that incorporates a membrane to study stratified 3D cell populations for skin tissue engineering. The DCB provides adjacent flow lines within a common chamber; the inclusion of the membrane regulates flow layering or mixing, which can be exploited to produce layers or gradients of cell populations in the scaffolds. Computational modeling and experimental assays were used to study the transport phenomena within the bioreactor. Molecular transport across the membrane was defined by a balance of convection and diffusion; the symmetry of the system was proven by its bulk convection stability, while the movement of molecules from one flow line to the other is governed by coupled convection-diffusion. This balance allowed the perfusion of two different fluids, with the membrane defining the mixing degree between the two.The bioreactor sustained two adjacent cell populations for 28 days, and was used to induce indirect adipogenic differentiation of mesenchymal stem cells due to molecular cross-talk between the populations. We successfully developed a platform that can study the dermis-hypodermis complex to address limitations in skin tissue engineering. Furthermore, the DCB can be used for other multilayered tissues or the study of communication pathways between cell populations.

Purpose This paper aims to study the effects of part orientation during the 3D printing process, particularly to the case of using continuous digital light processing (cDLP) technology. Design/methodology/approach The effects of print orientation on the print accuracy of microstructural features were assessed using microCT imaging and mechanical properties of cDLP microporous scaffolds were characterized under simple compression and complex biaxial loading. Resin viscosity was also quantified to incorporate this factor in the printing discussion. Findings The combined effect of print resin viscosity and the orientation and spacing of pores within the structure alters how uncrosslinked resin flows within the construct during cDLP printing. Microstructural features in horizontally printed structures exhibited greater agreement to the design dimensions than vertically printed constructs. While cDLP technologies have the potential to produce mechanically isotropic solid constructs because of bond homogeneity, the effect of print orientation on microstructural feature sizes can result in structurally anisotropic porous constructs. Originality/value This work is useful to elucidate on the specific capabilities of 3D printing cDLP technology. The orientation of the part can be used to optimize the printing process, directly altering parameters such as the supporting structures required, print time, layering, shrinkage or surface roughness. This study further detailed the effects on the mechanical properties and the print accuracy of the printed scaffolds.