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The effect of physical cues on the stem cell differentiation

Article  in  Current Stem Cell Research & Therapy · December 2018

DOI: 10.2174/1574888X14666181227120706

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Current Stem Cell Research & Therapy, 2019, 14, 000-000 1

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The Effect of Physical Cues on the Stem Cell Differentiation

Mehrdad Moosazadeh Moghaddam1, Shahin Bonakdar2, Mona Rastegar Shariatpanahi3, Mohammad

Ali Shokrgozar2,* and Shahab Faghihi1,*

1
Stem Cell and Regenerative Medicine Group, National Institute of Genetic Engineering and Biotechnology (NIGEB),
Tehran, 14965/161, Iran; 2National Cell Bank, Pasteur Institute of Iran, Tehran 3159915111, Iran; 3Department of Bio-
chemistry, Payame Noor University, Tehran, Iran

Abstract: Development of multicellular organisms is a very complex and organized process during

ARTICLE HISTORY
Received: September 27, 2018
Revised: November 05, 2018
Accepted: December 13, 2018
DOI:
10.2174/1574888X14666181227120706
which cells respond to various factors and features in extracellular environments. It has been demon-
strated that during embryonic evolvement, under certain physiological or experimental conditions, un-
specialized cells or stem cells can be induced to become tissue or organ-specific cells with special func-
tions. Considering the importance of physical cues in stem cell fate, the present study reviews the role
of physical factors in stem cells differentiation and discusses the molecular mechanisms associated with
these factors.

Keywords: Stem cell, differentiation, physical cues, molecular mechanisms.

INTRODUCTION PHYSICAL CUES AND STEM CELL FATE

Throughout the early stages of life and growth, stem cells
show the exceptional capability to evolve into numerous
distinct cell types. Stem cells are unspecialized cells without
any certain task potential to renew themselves during cell
division. Moreover, they are inducible by creating specific
physiological or experimental intervention [1]. These cells
can transform into specified cells or organs with certain roles
and therefore, provide pioneer cells to be used in the treat-
ment of degenerative genetic disorders such as damages gen-
erated by inflammation. Nevertheless, inducting and regulat-
ing cell differentiation has always been a struggle in regen-
erative medicine [2, 3]. Fate decision for stem cells (growth,
differentiation, and apoptosis) needs a distinctive program
with several targets in multiple pathways in order to initiate a
cellular cascade response [4, 5]. Soluble signals (i.e. growth
factors, cytokines), cell-extracellular matrix (ECM), and cell-
cell contacts have been proven to contribute to stem cell dif-
ferentiation [6]. The influential role of these physical cues in
stem cell destination and the associated molecular mecha-
nisms is discussed as follows.
*Address correspondence to these authors at the Stem cell and regenerative
medicine group, National Institute of Genetic Engineering and Biotechnol-
ogy (NIGEB), Tehran 14965/161, Iran;
Tel: +98 21 4478 7386; Fax: +98 21 4478 7386;
E-mails: sfaghihi@nigeb.ac.ir; Shahabeddin.faghihi@mail.mcgill.ca
*National Cell Bank, Pasteur Institute of Iran, Tehran 3159915111, Iran;
Email: mashokrgozar@pasteur.ac.ir
Stem cell phenotypes including self-renovation and dif-
ferentiation can be outstandingly influenced by different
biological and chemical soluble elements such as hormones,
growth factors, and other small components. Although, many
of their factor-mediated signaling pathways are not exactly
recognized yet. Numerous studies have demonstrated the
role of physical cues in managing the stem cells fate [6-8].
Basically, according to the performance and location of the
physical factors, cells are exposed to a wide range of physi-
cal cues in vivo, although pursuant to the nature of these
physical cues located in ECM, they can be classified into
three main groups namely, matrix stiffness,mechanical
forces, and surface topography (Fig. 1) [9-11].
Matrix Stiffness
The resistance magnitude of extracellular scaffold against
deformation is described as matrix stiffness. The cells spread
on stiffer matrix more than soft substrates and migrate to-
wards the areas with higher elastic modulus. Substrate stiff-
ness also regulates some other cell events including adhe-
sion, signaling of tyrosine, as well as the proliferation of
fibroblasts, smooth muscle cells, and chondrocytes [12]. For
instance, Engler et al. showed that bone marrow mesenchy-
mal stem cells (BMMSCs) differentiate into various tissue-
specific lineages in response to the stiffness of matrixes’
substrates imitating the stiffness of brain (0.1-1 kPa), muscle
(8-17 kPa), and pre-mineralized bone (25-40 kPa) [13]. Ad-
ditionally, modulated stiffness was used as a cellular analog

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