Mechanics of Stem Cells in Regenerative Medicine

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 11766

Special Issue Editor


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Guest Editor
Associate Professor of Mechanical Engineering, Southern Illinois University, Carbondale, IL, USA
Interests: mechanobiology; stem cell mechanics; cancer mechanics

Special Issue Information

Dear Colleagues,

Tissue and organ failure are becoming a major health problem around the world. To this end, pluripotent stem cells can provide unlimited cell supply in a laboratory setting for cell-based therapy. However, cell lineage control can become a limiting factor. Past studies have demonstrated pluripotent stem cell lineage specification via small molecules and/or physical factors including mechanical forces, microenvironment properties, extracellular matrix, surface topography, geometric regulations, etc. In particular, physical forces, whether endogenously generated or externally applied, play a vital role in cell fate decisions. Recent developments in single-molecule techniques may allow force modulation with a pico-Newton resolution that can be applied in stem cell fate decision making. Further research is necessary to understand the underlying mechanisms of cell lineage specification for application in regenerative medicine.

In this Special Issue, we welcome both original works as well as review articles related to the mechanics of pluripotent stem cells in regenerative medicine. In addition, studies focused on multipotent stem cells in regenerative medicine are welcome.

Dr. Farhan Chowdhury
Guest Editor

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Keywords


  • Pluripotent stem cells
  • Multipotent stem cells
  • Mechanics
  • Extracellular matrix
  • Forces
  • Microenvironment

Published Papers (4 papers)

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Research

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13 pages, 3115 KiB  
Article
Reduced Cell–ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation
by Kshitij Amar, Sanjoy Saha, Avishek Debnath, Chun Hung Weng, Arpan Roy, Kyu Young Han and Farhan Chowdhury
Cells 2023, 12(2), 326; https://doi.org/10.3390/cells12020326 - 15 Jan 2023
Viewed by 2464
Abstract
Mechanoregulation of cell–extracellular matrix (ECM) interactions are crucial for dictating pluripotent stem cell differentiation. However, not all pluripotent cells respond homogeneously which results in heterogeneous cell populations. When cells, such as mouse epiblast stem cells (EpiSCs), are cultured in clusters, the heterogeneity effect [...] Read more.
Mechanoregulation of cell–extracellular matrix (ECM) interactions are crucial for dictating pluripotent stem cell differentiation. However, not all pluripotent cells respond homogeneously which results in heterogeneous cell populations. When cells, such as mouse epiblast stem cells (EpiSCs), are cultured in clusters, the heterogeneity effect during differentiation is even more pronounced. While past studies implicated variations in signaling pathways to be the root cause of heterogeneity, the biophysical aspects of differentiation have not been thoroughly considered. Here, we demonstrate that the heterogeneity of EpiSC differentiation arises from differences in the colony size and varying degrees of interactions between cells within the colonies and the ECM. Confocal imaging demonstrates that cells in the colony periphery established good contact with the surface while the cells in the colony center were separated by an average of 1–2 µm from the surface. Traction force measurements of the cells within the EpiSC colonies show that peripheral cells generate large tractions while the colony center cells do not. A finite element modeling of EpiSC colonies shows that tractions generated by the cells at the colony periphery lift off the colony center preventing the colony center from undergoing differentiation. Together, our results demonstrate a biophysical regulation of heterogeneous EpiSC colony differentiation. Full article
(This article belongs to the Special Issue Mechanics of Stem Cells in Regenerative Medicine)
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19 pages, 5234 KiB  
Article
The Synergistic Effect of Cyclic Tensile Force and Periodontal Ligament Cell-Laden Calcium Silicate/Gelatin Methacrylate Auxetic Hydrogel Scaffolds for Bone Regeneration
by Jian-Jr Lee, Hooi-Yee Ng, Yen-Hong Lin, Ting-Ju Lin, Chia-Tze Kao and Ming-You Shie
Cells 2022, 11(13), 2069; https://doi.org/10.3390/cells11132069 - 29 Jun 2022
Cited by 14 | Viewed by 2486
Abstract
The development of 3D printing technologies has allowed us to fabricate complex novel scaffolds for bone regeneration. In this study, we reported the incorporation of different concentrations of calcium silicate (CS) powder into fish gelatin methacrylate (FGelMa) for the fabrication of CS/FGelMa auxetic [...] Read more.
The development of 3D printing technologies has allowed us to fabricate complex novel scaffolds for bone regeneration. In this study, we reported the incorporation of different concentrations of calcium silicate (CS) powder into fish gelatin methacrylate (FGelMa) for the fabrication of CS/FGelMa auxetic bio-scaffolds using 3D printing technology. Our results showed that CS could be successfully incorporated into FGelMa without influencing the original structural components of FGelMa. Furthermore, it conveyed that CS modifications both the mechanical properties and degradation rates of the scaffolds were improved in accordance with the concentrations of CS upon modifications of CS. In addition, the presence of CS enhanced the adhesion and proliferation of human periodontal ligament cells (hPDLs) cultured in the scaffold. Further osteogenic evaluation also confirmed that CS was able to enhance the osteogenic capabilities via activation of downstream intracellular factors such as pFAK/FAK and pERK/ERK. More interestingly, it was noted that the application of extrinsic biomechanical stimulation to the auxetic scaffolds further enhanced the proliferation and differentiation of hPDLs cells and secretion of osteogenic-related markers when compared to CS/FGelMa hydrogels without tensile stimulation. This prompted us to explore the related mechanism behind this interesting phenomenon. Subsequent studies showed that biomechanical stimulation works via YAP, which is a biomechanical cue. Taken together, our results showed that novel auxetic scaffolds could be fabricated by combining different aspects of science and technology, in order to improve the future chances of clinical applications for bone regeneration. Full article
(This article belongs to the Special Issue Mechanics of Stem Cells in Regenerative Medicine)
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Review

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29 pages, 4919 KiB  
Review
Frontier Review of the Molecular Mechanisms and Current Approaches of Stem Cell-Derived Exosomes
by Liang-Yun Chen, Ting-Wan Kao, Chang-Cyuan Chen, Noreen Niaz, Hsin-Lun Lee, Yu-Hsin Chen, Chia-Chun Kuo and Yao-An Shen
Cells 2023, 12(7), 1018; https://doi.org/10.3390/cells12071018 - 26 Mar 2023
Cited by 5 | Viewed by 3004
Abstract
Exosomes are effective therapeutic vehicles that may transport their substances across cells. They are shown to possess the capacity to affect cell proliferation, migration, anti-apoptosis, anti-scarring, and angiogenesis, via the action of transporting molecular components. Possessing immense potential in regenerative medicine, exosomes, especially [...] Read more.
Exosomes are effective therapeutic vehicles that may transport their substances across cells. They are shown to possess the capacity to affect cell proliferation, migration, anti-apoptosis, anti-scarring, and angiogenesis, via the action of transporting molecular components. Possessing immense potential in regenerative medicine, exosomes, especially stem cell-derived exosomes, have the advantages of low immunogenicity, minimal invasiveness, and broad clinical applicability. Exosome biodistribution and pharmacokinetics may be altered, in response to recent advancements in technology, for the purpose of treating particular illnesses. Yet, prior to clinical application, it is crucial to ascertain the ideal dose and any potential negative consequences of an exosome. This review focuses on the therapeutic potential of stem cell-derived exosomes and further illustrates the molecular mechanisms that underpin their potential in musculoskeletal regeneration, wound healing, female infertility, cardiac recovery, immunomodulation, neurological disease, and metabolic regulation. In addition, we provide a summary of the currently effective techniques for isolating exosomes, and describe the innovations in biomaterials that improve the efficacy of exosome-based treatments. Overall, this paper provides an updated overview of the biological factors found in stem cell-derived exosomes, as well as potential targets for future cell-free therapeutic applications. Full article
(This article belongs to the Special Issue Mechanics of Stem Cells in Regenerative Medicine)
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14 pages, 1915 KiB  
Review
Roles of Cartilage-Resident Stem/Progenitor Cells in Cartilage Physiology, Development, Repair and Osteoarthritis
by Wei Xu, Wei Wang, Da Liu and Dongfa Liao
Cells 2022, 11(15), 2305; https://doi.org/10.3390/cells11152305 - 27 Jul 2022
Cited by 6 | Viewed by 2843
Abstract
Osteoarthritis (OA) is a degenerative disease that causes irreversible destruction of articular cartilage for which there is no effective treatment at present. Although articular cartilage lacks intrinsic reparative capacity, numerous studies have confirmed the existence of cartilage-resident stem/progenitor cells (CSPCs) in the superficial [...] Read more.
Osteoarthritis (OA) is a degenerative disease that causes irreversible destruction of articular cartilage for which there is no effective treatment at present. Although articular cartilage lacks intrinsic reparative capacity, numerous studies have confirmed the existence of cartilage-resident stem/progenitor cells (CSPCs) in the superficial zone (SFZ) of articular cartilage. CSPCs are characterized by the expression of mesenchymal stromal cell (MSC)-related surface markers, multilineage differentiation ability, colony formation ability, and migration ability in response to injury. In contrast to MSCs and chondrocytes, CSPCs exhibit extensive proliferative and chondrogenic potential with no signs of hypertrophic differentiation, highlighting them as suitable cell sources for cartilage repair. In this review, we focus on the organizational distribution, markers, cytological features and roles of CSPCs in cartilage development, homeostasis and repair, and the application potential of CSPCs in cartilage repair and OA therapies. Full article
(This article belongs to the Special Issue Mechanics of Stem Cells in Regenerative Medicine)
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