Altering Kinetics of Polymerization Can Modulate Mesenchymal Stem Cells Interaction with 3D Matrix

Cardiac c-kit cells show promise in regenerating an injured heart. While heart disease commonly affects elderly patients, it is unclear if autologous cardiac c-kit cells are functionally competent and applicable to these patients. This study characterised cardiac c-kit cells (CCs) from aged mice and studied the effects of human Wharton’s Jelly-derived mesenchymal stem cells (MSCs) on the growth kinetics and cardiac differentiation of aged CCs in vitro. CCs were isolated from 4-week- and 18-month-old C57/BL6N mice and were directly co-cultured with MSCs or separated by transwell insert. Clonogenically expanded aged CCs showed comparable telomere length to young CCs. However, these cells showed lower Gata4, Nkx2.5, and Sox2 gene expressions, with changes of 2.4, 3767.0, and 4.9 folds, respectively. Direct co-culture of both cells increased aged CC migration, which repopulated 54.6 ± 4.4% of the gap area as compared to aged CCs with MSCs in transwell (42.9 ± 2.6%) and CCs without MSCs (44.7 ± 2.5%). Both direct and transwell co-culture improved proliferation in aged CCs by 15.0% and 16.4%, respectively, as traced using carboxyfluorescein succinimidyl ester (CFSE) for three days. These data suggest that MSCs can improve the growth kinetics of aged CCs. CCs retaining intact telomere are present in old hearts and could be obtained based on their self-renewing capability. Although these aged CCs with reduced growth kinetics are improved by MSCs via cell–cell contact, the effect is minimal.

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Alteration of 3D Matrix Stiffness Regulates Viscoelasticity of Human Mesenchymal Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22052441 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2441

Author(s):

Ting-Wei Kao ◽

Arthur Chiou ◽

Keng-Hui Lin ◽

Yi-Shiuan Liu ◽

Oscar Kuang-Sheng Lee

Keyword(s):

Mechanical Properties ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mean Square Displacement ◽

Human Mesenchymal Stem Cells ◽

Lineage Specification ◽

Particle Tracking Microrheology ◽

Chemically Induced ◽

3D Matrix ◽

Directing Effect

Human mesenchymal stem cells (hMSCs) possess potential of bone formation and were proposed as ideal material against osteoporosis. Although interrogation of directing effect on lineage specification by physical cues has been proposed, how mechanical stimulation impacts intracellular viscoelasticity during osteogenesis remained enigmatic. Cyto-friendly 3D matrix was prepared with polyacrylamide and conjugated fibronectin. The hMSCs were injected with fluorescent beads and chemically-induced toward osteogenesis. The mechanical properties were assessed using video particle tracking microrheology. Inverted epifluorescence microscope was exploited to capture the Brownian trajectory of hMSCs. Mean square displacement was calculated and transformed into intracellular viscoelasticity. Two different stiffness of microspheres (12 kPa, 1 kPa) were established. A total of 45 cells were assessed. hMSCs possessed equivalent mechanical traits initially in the first week, while cells cultured in rigid matrix displayed significant elevation over elastic (G′) and viscous moduli (G″) on day 7 (p < 0.01) and 14 (p < 0.01). However, after two weeks, soft niches no longer stiffened hMSCs, whereas the effect by rigid substrates was consistently during the entire differentiation course. Stiffness of matrix impacted the viscoelasticity of hMSCs. Detailed recognition of how microenvironment impacts mechanical properties and differentiation of hMSCs will facilitate the advancement of tissue engineering and regenerative medicine.

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QuantifyingIn VitroGrowth and Metabolism Kinetics of Human Mesenchymal Stem Cells Using a Mathematical Model

Tissue Engineering Part A ◽

10.1089/ten.tea.2008.0328 ◽

2009 ◽

Vol 15 (9) ◽

pp. 2653-2663 ◽

Cited By ~ 35

Author(s):

Gustavo Higuera ◽

Deborah Schop ◽

Frank Janssen ◽

Riemke van Dijkhuizen-Radersma ◽

Ton van Boxtel ◽

...

Keyword(s):

Mathematical Model ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

Kinetics Of

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Chitosan-Collagen 3D Matrix Mimics Trabecular Bone and Regulates RANKL-Mediated Paracrine Cues of Differentiated Osteoblast and Mesenchymal Stem Cells for Bone Marrow Macrophage-Derived Osteoclastogenesis

Biomolecules ◽

10.3390/biom9050173 ◽

2019 ◽

Vol 9 (5) ◽

pp. 173 ◽

Cited By ~ 4

Author(s):

Jeevithan Elango ◽

Kandasamy Saravanakumar ◽

Saeed Ur Rahman ◽

Yves Henrotin ◽

Joe M. Regenstein ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Trabecular Bone ◽

3D Structure ◽

Three Dimensional ◽

Joint Disease ◽

Dimensional Structure ◽

Bone Homeostasis ◽

3D Matrix

Recent studies have identified the regulatory mechanism of collagen in bone ossification and resorption. Due to its excellent bio-mimicry property, collagen is used for the treatment of several bone and joint disease such as arthritis, osteoporosis, and osteopenia. In bone, the biological action of collagen is highly influenced by the interactions of other bone materials such as glycosaminoglycan and minerals. In view of the above perceptions, collagen was crosslinked with chitosan, hydroxyapatite (H), and chondroitin sulfate (Cs), to produce a natural bone-like 3D structure and to evaluate its effect on bone homeostasis using bone marrow mesenchymal stem cells, osteoblast, and bone marrow macrophages. The XRD and micro-CT data confirmed the arrangement of H crystallites in the chitosan-collagen-H-Cs (CCHCs) three-dimensional (3D)-matrix and the three-dimensional structure of the matrix. The stimulatory osteoblastogenic and exploitive osteoclastogenic activity of 3D-matrices were identified using differentiated osteoblasts and osteoclasts, respectively. Besides, osteogenic progenitor’s paracrine cues for osteoclastogenesis showed that the differentiated osteoblast secreted higher levels of RANKL to support osteoclastogenesis, and the effect was downregulated by the CCHCs 3D-matrix. From that, it was hypothesized that the morphology of the CCHCs 3D-matrix resembles trabecular bone, which enhances bone growth, limits bone resorption, and could be a novel biomaterial for bone tissue engineering.

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