Manipulation of Stem Cells Fates: The Master and Multifaceted Roles of Biophysical Cues of Biomaterials

Abstract Background The niche of tissue development in vivo involves the growth matrix, biophysical cues and cell-cell interactions. Although natural extracellular matrixes may provide good supporting for seeding cells in vitro, it is evitable to destroy biophysical cues during decellularization. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair. Results In the study, a hybrid hydrogel was developed by incorporating single-wall carbon nanotubes (SWCNTs) into heart-derived extracellular matrixes. Interestingly, insoluble SWCNTs were well dispersed in hybrid hydrogel solution via the interaction with extracellular matrix proteins. Importantly, an augmented integrin-dependent niche was reconstructed in the hybrid hydrogel, which could work like biophysical cues to activate integrin-related pathway of seeding cells. As supporting scaffolds in vitro, the hybrid hydrogels were observed to significantly promote seeding cell adhesion, differentiation, as well as structural and functional development towards mature cardiac tissues. As injectable carrier scaffolds in vivo, the hybrid hydrogels were then used to delivery stem cells for myocardial repair in rats. Similarly, significantly enhanced cardiac differentiation and maturation(12.5 ± 2.3% VS 32.8 ± 5%) of stem cells were detected in vivo, resulting in improved myocardial regeneration and repair. Conclusions The study represented a simple and powerful approach for exploring bioactive scaffold to promote stem cell-based tissue repair. Graphic abstract

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Bio-mimicking Shear Stress Environments for Enhancing Mesenchymal Stem Cell Differentiation

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200408113630 ◽

2020 ◽

Vol 15 (5) ◽

pp. 414-427

Author(s):

Seep Arora ◽

Akshaya Srinivasan ◽

Chak Ming Leung ◽

Yi-Chin Toh

Keyword(s):

Stem Cells ◽

Shear Stress ◽

Stem Cell ◽

Stem Cell Differentiation ◽

In Vitro Differentiation ◽

Msc Differentiation ◽

Biophysical Cues

Mesenchymal stem cells (MSCs) are multipotent stromal cells, with the ability to differentiate into mesodermal (e.g., adipocyte, chondrocyte, hematopoietic, myocyte, osteoblast), ectodermal (e.g., epithelial, neural) and endodermal (e.g., hepatocyte, islet cell) lineages based on the type of induction cues provided. As compared to embryonic stem cells, MSCs hold a multitude of advantages from a clinical translation perspective, including ease of isolation, low immunogenicity and limited ethical concerns. Therefore, MSCs are a promising stem cell source for different regenerative medicine applications. The in vitro differentiation of MSCs into different lineages relies on effective mimicking of the in vivo milieu, including both biochemical and mechanical stimuli. As compared to other biophysical cues, such as substrate stiffness and topography, the role of fluid shear stress (SS) in regulating MSC differentiation has been investigated to a lesser extent although the role of interstitial fluid and vascular flow in regulating the normal physiology of bone, muscle and cardiovascular tissues is well-known. This review aims to summarise the current state-of-the-art regarding the role of SS in the differentiation of MSCs into osteogenic, cardiovascular, chondrogenic, adipogenic and neurogenic lineages. We will also highlight and discuss the potential of employing SS to augment the differentiation of MSCs to other lineages, where SS is known to play a role physiologically but has not yet been successfully harnessed for in vitro differentiation, including liver, kidney and corneal tissue lineage cells. The incorporation of SS, in combination with biochemical and biophysical cues during MSC differentiation, may provide a promising avenue to improve the functionality of the differentiated cells by more closely mimicking the in vivo milieu.

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Effects of biophysical cues of 3D hydrogels on mesenchymal stem cells differentiation

Journal of Cellular Physiology ◽

10.1002/jcp.30042 ◽

2020 ◽

Author(s):

Yutong Guo ◽

Shufang Du ◽

Shuqi Quan ◽

Fulin Jiang ◽

Cai Yang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Biophysical Cues

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Electrical Stimulation of Adipose-Derived Stem Cells in 3D Nanofibrillar Cellulose Increases Their Osteogenic Potential

Biomolecules ◽

10.3390/biom10121696 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1696

Author(s):

Mesude Bicer ◽

Jonathan Sheard ◽

Donata Iandolo ◽

Samuel Y. Boateng ◽

Graeme S. Cottrell ◽

...

Keyword(s):

Stem Cells ◽

Electrical Stimulation ◽

Osteoporotic Fractures ◽

Bone Grafts ◽

Osteogenic Potential ◽

Ageing Population ◽

Adipose Derived Stem Cells ◽

Alizarin Red ◽

Nanofibrillar Cellulose ◽

Biophysical Cues

Due to the ageing population, there is a steadily increasing incidence of osteoporosis and osteoporotic fractures. As conventional pharmacological therapy options for osteoporosis are often associated with severe side effects, bone grafts are still considered the clinical gold standard. However, the availability of viable, autologous bone grafts is limited making alternative cell-based strategies a promising therapeutic alternative. Adipose-derived stem cells (ASCs) are a readily available population of mesenchymal stem/stromal cells (MSCs) that can be isolated within minimally invasive surgery. This ease of availability and their ability to undergo osteogenic differentiation makes ASCs promising candidates for cell-based therapies for bone fractures. Recent studies have suggested that both exposure to electrical fields and cultivation in 3D can positively affect osteogenic potential of MSCs. To elucidate the osteoinductive potential of a combination of these biophysical cues on ASCs, cells were embedded within anionic nanofibrillar cellulose (aNFC) hydrogels and exposed to electrical stimulation (ES) for up to 21 days. ES was applied to ASCs in 2D and 3D at a voltage of 0.1 V/cm with a duration of 0.04 ms, and a frequency of 10 Hz for 30 min per day. Exposure of ASCs to ES in 3D resulted in high alkaline phosphatase (ALP) activity and in an increased mineralisation evidenced by Alizarin Red S staining. Moreover, ES in 3D aNFC led to an increased expression of the osteogenic markers osteopontin and osteocalcin and a rearrangement and alignment of the actin cytoskeleton. Taken together, our data suggest that a combination of ES with 3D cell culture can increase the osteogenic potential of ASCs. Thus, exposure of ASCs to these biophysical cues might improve the clinical outcomes of regenerative therapies in treatment of osteoporotic fractures.

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