Tunable hydrogels for mesenchymal stem cell delivery: integrin ‐induced transcriptome alterations and hydrogel optimization for human wound healing

PEG ‐8‐norbornene (PEG‐8‐Nb) and the peptide cross‐linker GCRDVPMS↓MRGGDRCG (that degrades in response to MMP ‐1, 2, 3, 7, and 9) were reacted, with the aid of the photoinitiator LAP, in the presence of MSC to form 3D hydrogel cultures. Parallel cultures were established similarly but with the addition of cysteine‐functionalized integrin‐binding small molecules, RGDS or LLP2A. MSC transcriptome profil ing revealed that hydrogel cultures altered the expression of genes important for extracellular matrix production, glycosylation, metabolism, and gene epigenetic regulation. AbstractTherapeutic applications for mesenchymal stem/stromal cells (MSCs) are growing; however, the successful implementation of these therapies requires the development of appropriate MSC delivery systems. Hydrogels are ideally suited to cultivate MSCs but tuning hydrogel properties to match their specificin vivo applications remains a challenge. Thus, further characterization of how hydrogel ‐based delivery vehicles broadly influence MSC function and fate will help lead to the next generation of more intelligently designed delivery vehicles. To date, few attempts have been made to comprehensively characterize hydrogel impact on the MSC transcriptome. Herein we have synthesized cell‐ degradable hydrogels based on bio‐inert poly(ethylene glycol) (PEG) tethered with specific integrin‐binding small molecules and have characterized their resulting effect on the MSC transcriptome when ...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Regenerative Medicine Source Type: research