Perspective: Tissue-Engineering the Intestine- The Trials before the Trials
INTENS Consortium discuss experimental considerations and challenges for generating a tissue-engineered intestine for the treatment of short bowel syndrome, taking into account cell source, scaffold choice, and design strategy for achieving proper assembly and function.
Current cell and gene therapies with market authorization (Cuende et al., 2018) include multiple approaches for skin, cornea, bone, or cartilage and CAR-T cell therapies. In addition, pluripotent stem cells (PSCs) have been delivered into the immune-privileged space of the retina. This first-in-human progress occurred with single cell types that do not require spatial or mechanical obligations. However, moving to more complex tissues, such as the intestine, presents increased obstacles such as motility, numerous differentiated cell types, three-dimensional convolution, conductance of luminal flow, and microbial interaction. Even for partial organ replacement, which might be clinically useful in certain cases, these requirements must be fulfilled by any therapeutically viable tissue-engineered candidate.
Clevers, H., Conder, R.K., Li, V.S.W., Lutolf, M.P., Vallier, L., Chan, S., Grikscheit, T.C., Jensen, K.B., De Coppi, P. (2019) Tissue-Engineering the intestine: The Trials before the Trials. Cell Stem Cell, 24, 855-859, doi: 10.1016/j.stem.2019.04.018.
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The overall aim of the INTENS Consortium is to deliver a functional bowel reconstruction to patients with this rare disease (SBS) through an autologous tissue engineering strategy, overcoming the shortage of organs, and avoiding the need for immunosuppression. It will be achieved by identifying the best autologous cell source; providing the ideal scaffold; engineering functional intestine for transplantation and engaging with patients, scientists and public. The work is designed to lead directly to a clinical trial for the application of the optimal protocol for tissue-engineered intestine.