Biophysics and dynamics of natural and engineered stem cell microenvironments
citation: Keung, A.J., Healy, K.E., Kumar, S., and Schaffer, D.V. (2009) Biophysics and dynamics of natural and engineered stem cell microenvironments, John Wiley & Sons
Summary:
In this review paper, mechanical induced stem cells differentiation is discussed. There are three different categories of inputs which are biomechanical, architectural and dynamic. Stem cells are known by their their ability to self-renew and to differentiate to one or more lineages. Previous research has build a strong foundation of knowledge on biochemical characteristic of the microenvironment and how this affect stem cells differentiation. Recent work has included biophysical and dynamic characteristics of the microenvironment.
From the aspect of biomechanics, one of the strong biophysical cues are stiffness, which varies between different types of tissues or even with individual tissues. Stiffness changes profoundly with aging or disease as well. Several experiments have been conducted to demonstrate the growth, survival and motility of many differentiated cell types can be controlled and regulated by stiffness of substrate. Engler et al. did research on stiffness induced differentiation of MSCs, human mesenchymal stem cells. in combination with soluble cues, ployacrylamide gels that mimics the stiffnesses of neural, muscle, and bone tissues can induce differentiation of MSCs into corresponding cell types. Further study found that MSCs on substrates mimicking fat and bone marrow retain MSCs in quiescent state.
in vitro study also shows that NSCs can be jointly regulated by soluble factors and ECM stiffness. percent of NSCs differentiated into neurons can shifted from less than 40% on hard surfaces to more than 90% on soft surfaces. in addition, embryonic cardiomyocytes beat optimally on substrates with similar stiffness with heart tissues and abolish myofibrillogenesis and beating on stiffer substrates.
In addition to stiffness, shear stress is also one of the biophycal cues that can induce differentiation. from this paper the author states that "exposure of MSCs to shear stress in vitro increases proliferation endothelial differentiation and production of angiogenic factors." MSCs embedded in porous polymer or collagen scaffolds can have osteogenesis under high shear stress.
Cyclic strain is a kind of mechanical stresses that can be resulted from many possible sources. Cyclic strain is imposed on cells by load-bearing tissues, the cardiovascular system. With combination of shear stress and cyclic strain, MSCs can differentiate into muscle tissues compared with static cultures. These studies suggest that stem cells may generate appropriate cell types in respond to cyclic strain.
Geometry can also determine the lineages cells can differentiate into. The author says "Cells cultured on the small islands appeared morphologically rounded and subsequently differentiated almost exclusively into adipocytes, whereas those on larger islandes flattened and differentiated predominantly into osteoblasts."
This paper is very clear on every topics they discussed, it also includes definitions for several special terms in this paper. The only possible improvement I can suggest is that the author can include more papers on how those mechanical signals affect stem cells at the scale of focal adhesion. I would like to know more about why and how does those signals induce differentiation.
7 comments:
hey, are you guys the group that's also doing MSC differentiation through stiffness factors?
yes we are
I'm curious to know if any papers you read found a way to grade the effectiveness of the MSCs after they experienced the shear stress. Meaning, is the optimal amount of shear stress the MSCs experience in the body equal to the optimum shear stress that they undergo in vitro?
Also not sure if this is of interest but you should look into taking BioE 112: Cell Biomechanics. Discusses mechanotransduction and the role focal adhesion complex play in translating cytoskeletal force on the cell into changes in protein binding or enzymatic activity.
for the shear stress I have not done enough study but there are some papers addressing this optimal stiffness to induce differentiation of MSCs into corresponding cell lineages. One is Engler's paper in the reference and the other one is Pelham and Wang at 1997. Please search for those if you want further details.
and yes, I took BioE 112 last semester. I think you were in the same class too.
I was very interested by the line that stated that "MSCs embedded in porous polymer or collagen scaffolds can have osteogenesis under high shear stress." This seemed odd to me, since I would expect physiological high-shear areas to lie exclusively within vessel walls. It would be more intuitive for cells subjected to high shear to differentiate into either endothelial or smooth muscle cells, since those are the cell types in vivo that experience such conditions. Conversely, I would expect high compressive stresses to induce osteogenesis, since that kind of loading is most typical in actual bone tissue.
I read some papers similar to this nature regarding ECM stiffness and its effect on cell differentiation. However, those papers all mention how a change in stiffness leads to a change in cell adhesion. I know that this just implies that the cell mechanosensing changes the behavior of the cell, but I was wondering if there was a specific link to adhesion and differentiation of MSC. I haven't taken 112, so I dont know if there is any specific pathway or anything.
Do the papers mention the methods used to determine stiffness? I have only worked with hydrogel stiffness as tested by rheology (which applies shear stresses) and I'm curious to know if the researchers used different characterization methods. Also, the paper seems to focus heavily on the mechanical physics of the microenvironments, did the researchers delve into chemical cues at all?
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