Understanding Stem Cell Microenvironment and its Engineering Methods for Regenerative Medicine Srishti Chakraborty, M.Tech National Institute of Technology, Rourkela
Abstract
Methods and Materials
The microenvironment within which a specific category of stem cells differentiate, and grow is known as the stem cell niche. In its niche, the stem cells experience several physical, chemical, and biological stimulations from their neighbouring cells as well as the extracellular matrix, which impact their pluripotency. The niche serves a plethora of functions in regard to the inhabiting stem cells, including a balance between quiescence, self-renewal and differentiation, modulation of cell behaviour, and protection against the accumulation of gene mutations which might lead to cancer cell formation. This review highlights how •
stem cells interact with their environment
•
how prone they are to degradation in their niche.
Background Physical cues, as listed below, have been found to influence stem cell functions invariably :
Results and Discussion
Physical microenvironments of stem cells were engineered using the following mechanisms: A. B. C.
Micro- and nanofabrication-based
Material-based approaches Mechanical-force-based approaches Micro- and nano-fabrication-based approaches
Mechanical-forcebased
•Polymers Material- •Ceramics •Substrate stiffness based
Material-based
•Cyclic strain Mechanica •Shear stress l-forcebased
The in-vivo characteristics are hard to replicate in-vitro using only material and mechanical-force based approaches as they cannot succeed at creating the 3D microenvironment of the stem cells. This is where micro- and nano-fabrication-based approaches triumph over them by stimulating cues like spatiotemporal physical and chemical gradients, surface topography and dynamic mechanical microenvironment, thereby inducing a niche similar to in-vivo conditions.
•Bottom-up assembly Micro- and •Topography patterning nano•Organ-on-a-Chip fabrication -based
According to a study by Khetan, S. et al. , human mesenchymal stem cell (hMSC) differentiation is controlled by degradationmediated cellular traction.
Stem cell
-High degree
of cell-spreading -High traction
-Osteogenesis
of cellspreading
-Low traction -Adipogenesis
Biological cues (hormones, growth factors)
Chemical cues (released chemicals)
Physical cues
Figure 1. Stem cell microenvironment engineering approaches. From “Engineering physical microenvironment for stem cell based regenerative medicine”, Han et al, June 2014, Drug Discovery Today, 19, 767.
Approach
Substrate stiffness
Matrix Stiffness
Mechanical forces
Cyclic Strain
Topography
Muscular movement, blood flow, and gravity bearings determines stem cell fate.
-Low degree
Nanoscale and microscale structures in ECM affect cell arrangement.
Lineage of a stem cell depends on variations of its ECM stiffness.
Contact Srishti Chakraborty National Institute of Technology, Rourkela Email: srishtic98@gmail.com
Organ-ona-Chip
Method Muscle stem cells grown on Hydrogelcoated petri dishes of varying stiffness
MSC-laden 3D agarose hydrogel was subjected to Dynamic Compression
3D stiffness gradient within a hydrogel was established in a tube
i. Cell viability was maintained ii. Cells were capable of forming hematopoietic system in vivo in mice
Outcome Rigid coating- Lost pluripotency Soft coatingNumber doubled in a week
Enhancement of aggrecan and collagen II transcriptional activity was observed
Proliferation rate of MSCs cultured in softer regions was greater than those cultured in stiffer regions
•Bio-electrospraying
i. Control as well as AABJ cells showed similar properties ii. Control populated cells in nearannular mono‐layered cellular colonies while jetted cells made mono‐layered cellular tracks •Aerodynamically Assisted Biojetting
Conclusion Stem cell behavior is highly influenced by dynamic changes in their 3D microenvironment. However, the mechanism by which physical cues from the microenvironment affect stem cell fate and how stem cells respond to them is still unknown. Future experiments ought to be conducted in trying to engineer 3D microenvironments and comprehend the basis of biochemical and biophysical cues from them and finally, set the seeds for targeted stem cell differentiation.
References Han, Yu Long, et al. "Engineering physical microenvironment for stem cell based regenerative medicine." Drug discovery today 19.6 (2014): 763-773. 2. Wan, Peng-Xia, Bo-Wen Wang, and Zhi-Chong Wang. "Importance of the stem cell microenvironment for ophthalmological cell-based therapy." World journal of stem cells 7.2 (2015): 448. 3. Gattazzo, Francesca, Anna Urciuolo, and Paolo Bonaldo. "Extracellular matrix: a dynamic microenvironment for stem cell niche." Biochimica et Biophysica Acta (BBA)-General Subjects 1840.8 (2014): 2506-2519. 4. Khetan, Sudhir, et al. "Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels." Nature materials 12.5 (2013): 458-465. 5. Bartolovic, Kerol, et al. "The differentiation and engraftment potential of mouse hematopoietic stem cells is maintained after bio-electrospray." Analyst 135.1 (2010): 157-164. 1.