Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells

Jiang, Nizhou; Tian, Xiliang; Wang, Quanxiang; Hao, Jiayu; Jiang, Jian; Wang, Hong

doi:10.1007/s12015-023-10658-3

Cited by 13 publications

(3 citation statements)

References 206 publications

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“…ECMs derived from stem cells retain the specific functionality that can reflect in vivo microenvironment characteristics, and contain unique signaling networks to mediate cell behavior [ 115 , 116 ], which brings more opportunities to support peripheral nerve repair following injury. The ECMs derived from MSCs can effectively support stable cell expansion without heterogeneous reaction while maintaining the undifferentiated state of stem cells as well [ 117 ]. MSC-derived ECMs are demonstrated to prevent or reverse the senescence of stem cells, including neural progenitor cells (NPCs), bone marrow MSCs (BMSCs), and umbilical cord MSCs, thereby maintaining their ability to proliferate and differentiate.…”

Section: Functional Properties and Mechanisms Of Cd-ecmsmentioning

confidence: 99%

Engineering cell-derived extracellular matrix for peripheral nerve regeneration

Xu,

Liu,

Ahmad

et al. 2024

Materials Today Bio

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Section: Functional Properties and Mechanisms Of Cd-ecmsmentioning

confidence: 99%

Engineering cell-derived extracellular matrix for peripheral nerve regeneration

Xu,

Liu,

Ahmad

et al. 2024

Materials Today Bio

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“…However, for mesenchymal stem cells (MSC) or other migratory cells, collagen may provide tracks for moving to the injury site [2]. The MSCs are undifferentiated cells that have the potential to differentiate into various cell types, typically osteoblasts, chondrocytes, and adipocytes, and in some cases, fibroblasts or myofibroblasts [3,4]. The multipotent MSCs are found in various tissues, such as bone marrow, adipose tissue, umbilical cord, tooth pulp, and others, often considered as stem cell niches [5].…”

Section: Introductionmentioning

confidence: 99%

Early Stages of Ex Vivo Collagen Glycation Disrupt the Cellular Interaction and Its Remodelling by Mesenchymal Stem Cells—Morphological and Biochemical Evidence

Komsa-Penkova,

Altankov,

Dimitrov

et al. 2024

Preprint

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Mesenchymal stem cells (MSCs), whose main function is tissue repair, use collagen to restore the structural integrity of damaged tissue, maintaining its organization through concomitant remodelling. The non-enzymatic glycation of collagen is likely to compromise its communication with MSC, which indeed underlies various pathological conditions such as late complications of diabetes and aging. However, data on the effect of more early stages of collagen glycation on the MSC interaction are lacking. This study focused on the fate of in vitro glycated rat tail collagen (RTC) in contact with MSCs after its pre-exposure to glucose for 1 or 5 days. Using human adipose tissue-derived MSCs (ADMSCs), we showed that their interaction with glycated collagen is significantly altered, manifested morphologically by reduced cell spreading, less formation of focal adhesions, and weaker development of the actin cytoskeleton, further confirmed by ImageJ morphometric analysis. This suggests a poorer recognition of early glycated collagen by integrin receptors, possibly due to steric hindrance of their binding sites. These morphological events were also accompanied by greatly reduced fibril-like reorganization of adsorbed FITC-collagen (a sign of impaired remodeling), complemented by reduced sensitivity to proteases. The latter was confirmed in two ways: measuring directly FITC-collagen degradation by the attached cells and quantifying the proteolysis reduction upon exogenous addition of collagenase in a cell-free system. The mechanism of the observed effects is unclear, although differential scanning calorimetry confirmed the presence of weak structural changes in glycated collagen. All this led us to conclude that the reason for the morphological changes of ADMSCs is the impaired interaction with early-glycated collagen due to the hindrance of complementary sequences for integrins, which certainly also affects the mechanical remodeling of collagen. However, the impaired collagenolytic activity, together with the observed small changes in the thermal transition profile, undoubtedly indicate some internal changes in the structural organization of the collagen molecule occurring even at this early stage of glycation, which in turn contributes further to the impaired MSC remodeling activity.

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“…This fibrillar protein undergoes self-assembly into fibrils, a process critical for tissue mechanics and functionality [ 1 ] as fibrils act as scaffolds, supporting most cells in the body. The MSCs are undifferentiated cells [ 2 ], but they have the potential to differentiate into various cell types, typically osteoblasts, chondrocytes, adipocytes, and, in some cases, fibroblasts or myofibroblasts [ 3 ]. While residing in their niches, MSCs remain undifferentiated [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Early Stages of Ex Vivo Collagen Glycation Disrupt the Cellular Interaction and Its Remodeling by Mesenchymal Stem Cells—Morphological and Biochemical Evidence

Komsa-Penkova,

Dimitrov,

Todinova

et al. 2024

IJMS

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Mesenchymal stem cells (MSCs), pivotal for tissue repair, utilize collagen to restore structural integrity in damaged tissue, preserving its organization through concomitant remodeling. The non-enzymatic glycation of collagen potentially compromises MSC communication, particularly upon advancing the process, underlying various pathologies such as late-stage diabetic complications and aging. However, an understanding of the impact of early-stage collagen glycation on MSC interaction is lacking. This study examines the fate of in vitro glycated rat tail collagen (RTC) upon exposure to glucose for 1 or 5 days in contact with MSCs. Utilizing human adipose tissue-derived MSCs (ADMSCs), we demonstrate their significantly altered interaction with glycated collagen, characterized morphologically by reduced cell spreading, diminished focal adhesions formation, and attenuated development of the actin cytoskeleton. The morphological findings were confirmed by ImageJ 1.54g morphometric analysis with the most significant drop in the cell spreading area (CSA), from 246.8 μm2 for the native collagen to 216.8 μm2 and 163.7 μm2 for glycated ones, for 1 day and 5 days, respectively, and a similar trend was observed for cell perimeter 112.9 μm vs. 95.1 μm and 86.2 μm, respectively. These data suggest impaired recognition of early glycated collagen by integrin receptors. Moreover, they coincide with the reduced fibril-like reorganization of adsorbed FITC-collagen (indicating impaired remodeling) and a presumed decreased sensitivity to proteases. Indeed, confirmatory assays reveal diminished FITC-collagen degradation for glycated samples at 1 day and 5 days by attached cells (22.8 and 30.4%) and reduced proteolysis upon exogenous collagenase addition (24.5 and 40.4%) in a cell-free system, respectively. The mechanisms behind these effects remain uncertain, although differential scanning calorimetry confirms subtle structural/thermodynamic changes in glycated collagen.

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Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells

Cited by 13 publications

References 206 publications

Engineering cell-derived extracellular matrix for peripheral nerve regeneration

Engineering cell-derived extracellular matrix for peripheral nerve regeneration

Early Stages of Ex Vivo Collagen Glycation Disrupt the Cellular Interaction and Its Remodelling by Mesenchymal Stem Cells—Morphological and Biochemical Evidence

Early Stages of Ex Vivo Collagen Glycation Disrupt the Cellular Interaction and Its Remodeling by Mesenchymal Stem Cells—Morphological and Biochemical Evidence

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