Bioengineering mini functional thymic units with EAK16-II/EAKIIH6 self-assembling hydrogel

Abstract

Herein, we highlight the technical feasibility of generating a functional mini thymus with a novel hydrogel system, based on a peptide-based self-assembly platform that can induce the formation of 3-D thymic epithelial cell (TEC) clusters. Amphiphilic peptide EAK16-II co-assembled with its histidinylated analogue EAKIIH6 into beta-sheet fibrils. When adaptor complexes (recombinant protein A/G molecules loaded with both anti-His and anti-EpCAM IgGs) were added to the mix, TECs were tethered to the hydrogel and formed 3-D mini clusters. TECs bound to the hydrogel composites retained their molecular properties; and when transplanted into athymic nude mice, they supported the development of functional T-cells. These mini thymic units of TECs can be useful in clinical applications to reconstitute T-cell adaptive immunity.

Acute Thymic Involution and Mechanisms for Recovery

“…In addition to the therapeutic and mechanistic approaches described above, other techniques to reverse ATI may include the ablation of sex steroids (Goldberg et al 2010), supplementation with hormones such as growth hormone or prolactin (Dorshkind and Horseman 2000;Redelman et al 2008), application of small RNAs (Baltimore et al 2008;Khan et al 2014) and bio-engineering strategies (Palamaro et al 2013;Tajima et al 2015).…”

Local retention of antibodies in vivo with an injectable film embedded with a fluorogen-activating protein

“…The ability to vary the density of dL5 through intermixing the polypeptides allows mutual optimization of bulk physical properties and IgG loading and release kinetics. Because the pore size and tortuosity of the fibrillar matrix can be tuned by changing EAK16-II concentration, other agents, including small molecule drugs, or clusters of cells [50], may be encapsulated without impeding the ability to regulate IgG loading and release. In the presence of molar excess EAK16-II, dL5_EAK incorporates efficiently into the network, without disrupting the integrity of the fibrils [28].…”

Restoration of Thymus Function with Bioengineered Thymus Organoids

“…To improve the organization of TEC subsets in the bioengineered thymus, 3-D biofabrication tools to promote the aggregation of TECs can be utilized. Recently, we incorporated TEC-specific antibodies in a polypeptide-based, self-assembling hydrogel system and have successfully generated mini aggregates of TECs[68]. When these 3-D aggregates of TECs were transplanted into athymic nude mice, they could efficiently support T-lymphogenesis.…”