scholarly journals Biomimetic three-dimensional microenvironment for controlling stem cell fate

2011 ◽  
Vol 1 (5) ◽  
pp. 792-803 ◽  
Author(s):  
Hu Zhang ◽  
Sheng Dai ◽  
Jingxiu Bi ◽  
Kuo-Kang Liu

Stem cell therapy is an emerging technique which is being translated into treatment of degenerated tissues. However, the success of translation relies on the stem cell lineage commitment in the degenerated regions of interest. This commitment is precisely controlled by the stem cell microenvironment. Engineering a biomimetic three-dimensional microenvironment enables a thorough understanding of the mechanisms of governing stem cell fate. We review the individual microenvironment components, including soluble factors, extracellular matrix, cell–cell interaction and mechanical stimulation. The perspectives in creating the biomimetic microenvironments are discussed with emerging techniques.

2021 ◽  
Author(s):  
Diane L. Barber ◽  
Yi Liu ◽  
Efren Reyes ◽  
David Castillo-Azofeifa ◽  
Ophir D Klein ◽  
...  

Emerging evidence is revealing critical roles of intracellular pH (pHi) in development, but it remains unclear whether pHi regulates stem cell fate specification. We find that pHi dynamics is a key regulator of cell fate in the mouse intestinal stem cell lineage. We identify a pHi gradient along the intestinal crypt axis and find that dissipating this gradient inhibits crypt budding due to loss Paneth cell differentiation. Mechanistically, decreasing pHi biases intestinal stem cell fate toward the absorptive and away from the secretory lineage, by regulating the activity of the lineage transcription factor Atoh1. Our findings reveal a previously unrecognized role for pHi dynamics in the specification of cell fate within an adult stem cell lineage.


2015 ◽  
Vol 7 (4) ◽  
pp. 435-446 ◽  
Author(s):  
Sebastián L. Vega ◽  
Anandika Dhaliwal ◽  
Varun Arvind ◽  
Parth J. Patel ◽  
Nick R. M. Beijer ◽  
...  

Timely classification of stem cell lineage commitment in response to cell–microenvironment interactions using high content analysis of sub-nuclear protein organization.


2013 ◽  
Vol 12 (5) ◽  
pp. 458-465 ◽  
Author(s):  
Sudhir Khetan ◽  
Murat Guvendiren ◽  
Wesley R. Legant ◽  
Daniel M. Cohen ◽  
Christopher S. Chen ◽  
...  

Author(s):  
Mai T. Ngo ◽  
Victoria R. Barnhouse ◽  
Aidan E. Gilchrist ◽  
Christine J. Hunter ◽  
Joy N. Hensold ◽  
...  

AbstractBiomaterials that replicate patterns of microenvironmental signals from the stem cell niche offer the potential to refine platforms to regulate stem cell behavior. While significant emphasis has been placed on understanding the effects of biophysical and biochemical cues on stem cell fate, vascular-derived or angiocrine cues offer an important alternative signaling axis for biomaterial-based stem cell platforms. Elucidating dose-dependent relationships between angiocrine cues and stem cell fate are largely intractable in animal models and two-dimensional cell culture. In this study, we leverage microfluidic mixing devices to generate three-dimensional hydrogels containing lateral gradients in vascular density alongside murine hematopoietic stem cells (HSCs). Regional differences in vascular density can be generated via embossed gradients in cell, matrix, or growth factor density. HSCs co-cultured alongside vascular gradients reveal spatial patterns of HSC phenotype in response to angiocrine signals. Notably, decreased Akt signaling in high vessel density regions led to increased expansion of lineage-positive hematopoietic cells. This approach offers a combinatorial tool to rapidly screen a continuum of microenvironments with varying vascular, biophysical, and biochemical cues to reveal the influence of local angiocrine signals on HSC fate.


2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Silvia A. Ferreira ◽  
Meghna S. Motwani ◽  
Peter A. Faull ◽  
Alexis J. Seymour ◽  
Tracy T. L. Yu ◽  
...  

Abstract Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.


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