Endogenous Stem Cells in Homeostasis and Aging

Lim, Ji Eun; Son, Youngsook

doi:10.1007/s13770-017-0097-3

Cited by 19 publications

(12 citation statements)

References 174 publications

(210 reference statements)

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“…Osteoarthritis is a degenerative disease that strongly correlates with age [38,39]. Mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit a superior chondrogenic ability compared with those derived from non-joint tissues [1,40,41]; thus, they represent the best choice for the regeneration and repair of cartilage [40].…”

Section: Discussionmentioning

confidence: 99%

Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model

Mazzotti

Teti

Falconi

et al. 2019

Cells

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Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs’ biological characteristics and differentiation abilities remains unknown, and a full understanding of the mechanisms involved in cellular aging is lacking. The aim of this study was therefore to investigate the presence of age-related alterations in synovial fluid MSCs and their influence on the potential ability of MSCs to differentiate toward chondrogenic phenotypes. Synovial fluid MSCs, isolated from healthy equine donors from 3 to 40 years old, were cultured in vitro and stimulated towards chondrogenic differentiation for up to 21 days. An equine model was chosen due to the high degree of similarity of the anatomy of the knee joint to the human knee joint and as spontaneous disorders develop that are clinically relevant to similar human disorders. The results showed a reduction in cell proliferation correlated with age and the presence of age-related tetraploid cells. Ultrastructural analysis demonstrated the presence of morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy. Alcian blue assay and real-time PCR data showed a reduction of efficiency in the chondrogenic differentiation of aged synovial fluid MSCs compared to young MSCs. All these data highlighted the influence of aging on MSCs’ characteristics and ability to differentiate towards chondrogenic differentiation and emphasize the importance of considering age-related alterations of MSCs in clinical applications.

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Section: Discussionmentioning

confidence: 99%

Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model

Mazzotti

Teti

Falconi

et al. 2019

Cells

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“…Numerous reports have shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic bene t for GVHD and most clinical trials have used MSCs [5,14], nevertheless, the controversy about their safety and e cacy still remains. Although, BM is the main source of MSCs, the use of BM-MSCs is not always acceptable because of the invasive harvesting procedure, besides, the number of BMSCs declines with increasing age [15,16]. Placenta tissue-derived MSCs have the advantage of being readily available and easy to collect from a waste product, which has been reported to contain a population of multipotent stem cells exhibiting characteristics of MSCs [17].…”

Section: Discussionmentioning

confidence: 99%

Human Amniotic Mesenchymal Stem Cells Inhibit aGVHD in Humanized NPG Mice by Regulating Balance of Treg Versus T Effector Cells

Gao

et al. 2021

Preprint

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Background: Acute graft versus host disease(aGVHD) occurs when immunocompetent T cells in the donated tissue recognize the recipient as foreign after allo-HSCT, which can severely affect quality of life. Although previous studies indicated that MSC may be a salvage therapeutic agent for aGVHD, the mechanism is not yet fully clear. The aim of this study was to explore the therapeutic efficacy and underlying mechanisms of hAMSCs transplantation for humanized aGVHD mouse model.Methods: We established a novel xenogeneic (xeno)-aGVHD humanized mouse models by transplanting purified human T cells from peripheral blood into immunodeficient NOD-PrkdcscidIl2rγnull (NPG) mouse. In those mouse models, lymphocyte infiltration of target organs was detected by HE staining method and immunohistochemistry respectively. The biological characteristics of hAMSCs were investigated. hAMSCs labeled with GFP were administered to NPG mice to explore the homing ability of hAMSCs. Mice are divided into normal(control) group, aGVHD group and hAMSCs treatment group. After 3 days of injection of PBMC, hAMSCs and PBS were given into the different groups. T effector and Treg cells levels of each group in target organs were detected by flow cytometry and cytometric bead array (CBA).Results: We successfully established xenogeneic aGVHD “humanized model” by using NOD-PrkdcscidIl2rγnull (NPG) mice, which showed lymphocytes infiltration in the liver, spleen and lung. hAMSCs therapy improved systemic inflammation and inhibited aGVHD in humanized mouse through reduced villous blunting and lymphocyte infiltration into the lamina propria of the gut while reducing vascular endothelialitis and lymphocyte infiltration into the parenchyma of the liver and lung. In addition, hAMSCs suppresses xenogenesis CD3+/CD4+ and CD3+/CD8+ T cell concentration and increases the proportion of Treg cells. Our data also show that hAMSC can reduce the level of IL-17A, INF-γ, TNF and IL-2 that involved in the pathogenesis of aGVHD target organs.Conclusions: NPG murine environment is capable of activating human T cells to produce aGVHD pathology to mimic aGVHD in humans. hAMSCs controlled aGVHD by decreasing inflammatory cytokine secretion within target organs through modulating balance of Treg versus T effector cells in humanized mice.

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“…Besides, exogenous or endogenous stem cells have been shown to contribute to cardiac tissue regeneration by either differentiation into the vascular cell types or by paracrine mechanisms [ 42–45 ]. We also observed significant recruitment of CD29-positive MSCs in SP patch, IGF-1C patch and IGF-1C/SP patch-treated groups than that of the saline and patch-only groups.…”

Section: Discussionmentioning

confidence: 99%

In situ cardiac regeneration by using neuropeptide substance P and IGF-1C peptide eluting heart patches

Shafiq

Zhang

Zhu

et al. 2018

Regenerative Biomaterials

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Cardiovascular diseases cause huge socio-economic burden worldwide. Although a mammalian myocardium has its own limited healing capability, scaffold materials capable of releasing stem cell recruiting/engrafting factors may facilitate the regeneration of the infarcted myocardium. The aim of this research was to develop cardiac patches capable of simultaneously eluting substance P (SP) and insulin-like growth factor-1C (IGF-1C) peptide. Polycaprolactone/collagen type 1-based patches with or without SP and IGF-1C peptide were fabricated by co-electrospinning, which exhibited nanofibrous morphology. SP and IGF-1C/SP patches recruited significantly higher numbers of bone marrow-mesenchymal stem cells than that of the negative control and patch-only groups in vitro. The developed patches were transplanted in an infarcted myocardium for up to 14 days. Mice underwent left anterior descending artery ligation and received one of the following treatments: (i) sham, (ii) saline, (iii) patch-only, (iv) IGF-1C patch, (v) SP patch and (vi) IGF-1C/SP patch. SP and IGF-1C/SP patch-treated groups exhibited better heart function and attenuated adverse cardiac remodeling than that of the saline, patch-only and individual peptide containing cardiac patches. SP patch and IGF-1C/SP patch-treated groups also showed higher numbers of CD31-positive vessels and isolectin B4-positive capillaries than that of other groups. IGF-1C/SP-treated group also showed thicker left ventricular wall in comparison to the saline and patch-only groups. Moreover, IGF-1C/SP patches recruited significantly higher numbers of CD29-positive cells and showed less numbers of Tunel-positive cells compared with the other groups. These data suggest that SP and IGF-1C peptides may act synergistically for in situ tissue repair.

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Endogenous Stem Cells in Homeostasis and Aging

Cited by 19 publications

References 174 publications

Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model

Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model

Human Amniotic Mesenchymal Stem Cells Inhibit aGVHD in Humanized NPG Mice by Regulating Balance of Treg Versus T Effector Cells

In situ cardiac regeneration by using neuropeptide substance P and IGF-1C peptide eluting heart patches

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