Biophysical factors in the regulation of asymmetric division of stem cells

Abstract

Stem cells are a promising cell source for regenerative medicine due to their characteristics of self-renewal and differentiation. The intricate balance between these two cell fates is maintained by precisely controlled symmetric and asymmetric cell divisions. Asymmetric division has a fundamental importance in maintaining tissue homeostasis and in the development of multi-cellular organisms. For example, during development, asymmetric cell divisions are responsible for the formation of the body axis. Mechanistically, mitotic spindle dynamics determine the assembly and separation of chromosomes and regulate the orientation of cell division. Interestingly, symmetric and asymmetric cell division is not mutually exclusive and a range of factors are involved in such cell-fate decisions, the measurement of which can provide efficient and reliable information on the regenerative potential of a cell. The balance between self-renewal and differentiation in stem cells is controlled by various biophysical and biochemical cues. Although the role of biochemical factors in asymmetric stem cell division has been widely studied, the effect of biophysical cues in stem-cell self-renewal is not comprehensively understood. Herein, we review the biological relevance of stem-cell asymmetric division to regenerative medicine and discuss the influences of various intrinsic and extrinsic biophysical cues in stem-cell self-renewal. This review particularly aims to inform the clinical translation of efforts to control the self-renewal ability of stem cells through the tuning of various biophysical cues.

The dynamic(s) of adipose stem cell system, their survival, and cessation under the influence of electromagnetic fields

“…differentiation or stem cell-cancer stem cell transition. [ 3 23 24 ] The stem cell fate may be affected by EMF stimulation, especially in terms of ICR-like mechanism(s) influencing Ca 2+ ion concentration, thus changing cell division, microtubule dynamic instability, and division axis, leading to asymmetric stem cell division. [ 4 23 24 ]…”

Understanding the underlying mechanisms governing spindle orientation: How far are we from there?

“…It relies on the interaction of astral microtubules with cortical proteins to dictate spindle position and orientation 68,69 . Therefore, factors concerning spindle morphology and/or behaviour are likely to affect their orientation 70–72 . Moreover, cortical determinants and astral microtubules are not passive participants during this process.…”

“…Genes mentioned in this review and their homologues in different model organisms orientation [70][71][72]. Moreover, cortical determinants and astral microtubules are not passive participants during this process.…”

The role of Hippo signaling pathway and mechanotransduction in tuning embryoid body formation and differentiation

“…Stem cells react to a range of environmental cues in vitro to either self‐renew or regulate differentiation. These cues include both exogenous and endogenous biochemical factors, cell junctions, cell–matrix interactions, and mechanical stimuli (Barui & Datta, 2019; Perestrelo, Correia, Ramalho‐Santos, & Wirtz, 2018). The improvement of the differentiation efficiency of EBs by controlling the liquid flow in the culture system is a requisite (Kato, Matsumoto, & Kino‐oka, 2019).…”

“…The balance between self‐renewal and differentiation in the stem cells is controlled by a variety of biophysical and biochemical cues. Although the role of biochemical factors in stem cell asymmetric division is widely studied, the effect of biophysical cues in stem cell self‐renewal is not comprehensively understood (Barui & Datta, 2019). The forced agglomeration of the stem cells influences the aggregated cells via cell–cell and cell–matrix interactions, as well as the asymmetric or symmetric division of the stem cells, thereby affecting the differentiation of EBs (Morrison & Kimble, 2006).…”