Designing stem cell niches for differentiation and self-renewal

Abstract

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche. Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro. In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries.

Proteins and Peptides as Important Modifiers of the Polymer Scaffolds for Tissue Engineering Applications—A Review

“…Moreover, surface rigidity also dictates stem cell fate. In other words, surface stiffness acts as physical signal that allows them to differentiate towards specific cells [167,179,[181][182][183][184][185][186][187][188]. For instance, soft collagen-coated polyacrylamide gel (E = 1 kPa) did not support cell viability, spreading, or formation of the actin cytoskeleton, while the stiffer surface of such biomaterial (E equal to 8 kPa) enhanced adhesion and spreading of cells (studies on rat vascular smooth muscle cell line) [167,187].…”

Attachment and spatial organisation of human mesenchymal stem cells on poly(ethylene glycol) hydrogels

“…Once cells have been recruited to the defect site, they require specific cues that assign them their regenerative duties. These signals serve as lineage determinants, coaxing cells to reprogram into specific cell types [248]. Successful commitment results in tissue specific gene and protein profiles, while changes manifest in the ECM as well [249].…”

Choroid plexus‐derived miR‐204 regulates the number of quiescent neural stem cells in the adult brain

“…Therefore, an important cornerstone in understanding the regulation of neurogenesis within the adult brain, including its age‐related decline (Shook et al , ), is to decipher mechanisms controlling the balance between qNSC maintenance and activation. The neurogenic niche harboring NSCs has been proposed to be the key to control this balance and maintain the neurogenic potential in specific, spatially restricted brain areas (Donnelly et al , ). These niches provide unique support for neurogenesis, as the brain parenchyma outside these niches limits the neurogenic potential of endogenous or transplanted neuronal progenitors (Flax et al , ; Winkler et al , ; Fricker et al , ; Englund et al , ).…”