Biophysical Regulation of Stem Cell Differentiation

Abstract

Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells-the most broadly studied source of osteoblastic progenitors-undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loading-induced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche.

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

“…Regarding differentiation, this data agrees with previous works that demonstrated the osteogenic potential of osteocyte conditioned media upon stem cells [20,29], whilst the enhanced osteogenesis observed with addition of flow media is supported by work previously undertaken in our laboratory demonstrating enhanced early gene expression in MSCs [21]. This in vitro demonstration of indirect biophysical regulation of osteoprogenitors further highlights the important upstream mechanosensory role of the osteocyte and the importance of physical loading in regulating bones anabolic response [11,15,16,30].…”

“…Recent evidence suggests that this upstream role is predominantly fulfilled by osteocytes [11,12], which are ideally numbered and positioned within their lacunocanalicular network to coordinate mechanically-mediated secretion of biological signalling factors [13][14][15]. The mechanism by which osteocytes communicate with neighbouring precursor and/or effector cells is a topic of significant ongoing research [16]. It has been demonstrated that osteocytes communicate with osteoblasts via gap junctions [17], and osteoclasts via a paracrine mechanism [18,19], in both static and loaded conditions to regulate the bone remodelling cycle.…”

“…These data taken together form a strong argument for the role of the osteocyte as a co-ordinator of bone formation via control of precursor cells, particularly in response to mechanical stimulation. In spite of the mounting evidence of the osteocyte as the key regulator of this process, there is little knowledge of its interplay with the stem cell niche, particularly under physically loaded conditions [16].…”

Mechanical Stimulation of Cells Through Scaffold Design for Tissue Engineering

“…Modelling the constitutive behaviour of cells through biophysical signals poses a challenge. The stimuli reside in vivo, but the challenge is mimicking the properties in vitro [5]. Imitating stem cell biophysical niches with biomaterials could facilitate the production of large numbers of stem cells needed for in vitro regenerative medicine.…”

“…In recent years, researchers have tried to evaluate the signiicance of physical cues that inluence stem cells; such as stifness of cell culture substrates and other applied mechanical forces [6]. Several studies explore the regulation of stem cells via luid shear stress, hydrostatic pressure, ECM elasticity, substrate topography and tension [5]. However, how cells can sense mechanical forces or deformation and convert them into signals is not well understood.…”