Use of Tethered Hydrogel Microcoatings for Mesenchymal Stem Cell Equilibrium, Differentiation, and Self‐Organization into Microtissues

Abstract

Therapeutic adult mesenchymal stem cells (MSCs) lose multipotency and multilineage specialization in culture and after transplantation due to the absence of complex biological architecture. Here, it is shown that a transient ultrathin covering of permeable biomaterial can be differentially formulated to either preserve multipotency or induce multidifferentiation. Accordingly, populations of single, spherical MSCs in suspended media with high selectivity and specificity can be coated. Assembly of single, double, and triple hydrogel layers at MSC membranes is initiated by first attaching MSC‐specific immunoglobulins onto CD90 or Stro‐1 receptors and UEA‐1 and soybean lectins. A secondary biotinylated immunoglobulin is targeted for avidin binding, which becomes an attractor for biotinylated alginate or hyaluronate, which are subsequently stiffened and gelled, in situ around the entire cell surface. Alginate microcoatings permeated with mobile BMP‐2‐induced osteospecialized tissue, vascular endothelial growth factor (VEGF) induced microcapillary formation, while microcoatings, with selected basement membrane proteins, preserve the multipotent phenotype of MSCs, for continuing rounds of culture and directed specialization. Furthermore, forced packing of microcoated MSC populations creates prototypical tissue compartments: the coating partially simulating the extracellular matrix structures. Remarkably, microcoated MSC clusters show a tremendous simulation of a common embryological tissue transformation into the epithelium. Thus, confinement of free morphology exerts another control on tissue specialization and formation.

Isolation of Swine Bone Marrow Lin-/CD45-/CD133 + Cells and Cardio-protective Effects of its Exosomes

“…MSCs play an important role in bone defects, not only because of their multipotency but also as a source of cytokine supply. For adult SCs, mainly MSCs, translation from bench to clinical trials dates back to the late 1990s and early 2000s, when evidence for multipotentiality of MSCs was published by Osiris Therapeutics [ 53 ] and the first clinical trials were performed using MSCs [ 54 ]. MSCs have been shown to be safe and to promote heart function improvements [ 55 ].…”

Sequenced Somatic Cell Reprogramming and Differentiation Inside Nested Hydrogel Droplets

“…ECM Augmented Alginate-ECMp Material for Cell Adhesion and Organization: Cell interactivity of the alginate-ECMp framework improved by adding essential human ECM cell binding componentsprincipally representatives of the basement membrane (BM). Nanogram concentrations of laminin (0.3 mL per bead; derived from human placenta tissue) and collagen IV (0.3 mL per bead; from the human placenta), chondroitin sulphate (shark cartilage; 0.12 mL per bead) and RGD tripeptides (0.1 mL mL −1 GRGDS, Sigma) [7] which infuse into the alginate-ECMp solutions in making all the mm-sized fused droplets except for the intended differentiation mm-sized fused droplets, which inserted into the primary reprogramming host.…”