Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune Diseases

Lee, Hong Kyung; Lim, Sung Cil; Chung, In-Sung; Park, Yunsoo; Park, Ju Hee; Kim, Ju Young; Kim, Yong Guk; Hong, Jin Tae; Kim, Youngsoo; Han, Sang‐Bae

doi:10.4110/in.2014.14.2.81

Cited by 27 publications

(23 citation statements)

References 50 publications

(71 reference statements)

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“…TGF-b is an important factor in promoting corneal wound healing [3,27,42], and the TGF-b/ Smad2 axis is known as the canonical TGF-b signaling pathway [43]. Moreover, TGF-b serves as a secretory immune modulator of MSCs [44]. In this study, we observed that stromal rigidity enhanced TGF-b1, b2, and b3 production by MSCs ( Fig.…”

Section: Discussionsupporting

confidence: 49%

Stromal Tissue Rigidity Promotes Mesenchymal Stem Cell-Mediated Corneal Wound Healing Through the Transforming Growth Factor β Signaling Pathway

Yang

Hsieh

et al. 2016

Stem Cells

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The healing of a corneal epithelial defect is essential for preventing infectious corneal ulcers and subsequent blindness. We previously demonstrated that mesenchymal stem cells (MSCs) in the corneal stroma, through a paracrine mechanism, yield a more favorable therapeutic benefit for corneal wound re-epithelialization than do MSCs in the corneal epithelium. In this study, MSCs were grown on a matrix with the rigidity of the physiological human vitreous (1 kPa), corneal epithelium (8 kPa), or corneal stroma (25 kPa) for investigating the role of corneal tissue rigidity in MSC functions regarding re-epithelialization promotion. MSC growth on a 25-kPa dish significantly promoted the wound healing of human corneal epithelial (HCE-T) cells. Among growth factors contributing to corneal epithelial wound healing, corneal stromal rigidity selectively enhanced transforming growth factor-beta (TGF-β) secretion from MSCs. Inhibitors of TGF-β pan receptor, TGF-β receptor 1, and Smad2 dose dependently abrogated MSC-mediated HCE-T wound healing. Furthermore, MSCs growth on a matrix with corneal stromal rigidity enhanced the ability of themselves to promote corneal re-epithelialization by activating matrix metalloproteinase (MMP) expression and integrin β1 production in HCE-T cells through TGF-β signaling pathway activation. Smad2 activation resulted in the upregulation of MMP-2 and -13 expression in HCE-T cells, whereas integrin β1 production favored a Smad2-independent TGF-β pathway. Altogether, we conclude that corneal stromal rigidity is a critical factor for MSC-induced promotion of corneal re-epithelialization. The activation of the TGF-β signaling pathway, which maintains the balance between integrin and MMP expression, in HCE-T cells is the major pathway responsible for MSC-mediated wound healing. Stem Cells 2016;34:2525-2535.

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Section: Discussionsupporting

confidence: 49%

Stromal Tissue Rigidity Promotes Mesenchymal Stem Cell-Mediated Corneal Wound Healing Through the Transforming Growth Factor β Signaling Pathway

Yang

Hsieh

et al. 2016

Stem Cells

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“…Considerable experimental evidence shows that delivery of MSCs can lead to structural and functional improvement of many organs and tissues 3 . In line with these observations, we have previously shown in porcine renovascular disease that adipose tissue-derived MSCs improved stenotic kidney function and structure after renal revascularization 4, 5 and improved function in the non-revascularized stenotic-kidney 6 .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells

Eirin

Riester

Zhu

et al. 2014

Gene

239

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Mesenchymal stromal/stem cells (MSCs) are clinically useful for cell-based therapy, but concerns regarding their ability to replicate limit their human application. MSCs release extracellular vesicles (EVs) that mediate at least in part the paracrine effects of the parental cells. To understand the molecular basis of their biological properties, we characterized the RNA cargo of EVs from porcine adipose-tissue derived MSCs. Comprehensive characterization of mRNA and miRNA gene expression using high-throughput RNA sequencing (RNA-seq) revealed that EVs are selectively enriched for distinct classes of RNAs. For example, EVs preferentially express mRNA for transcription factors (e.g. MDFIC, POU3F1, NRIP1) and genes involved in angiogenesis (e.g. HGF, HES1, TCF4) and adipogenesis (e.g. CEBPA, KLF7). EVs also express Golgi apparatus genes (ARRB1, GOLGA4) and genes involved in TGF-β signaling. In contrast, mitochondrial, calcium signaling, and cytoskeleton genes are selectively excluded from EVs, possibly because these genes remain sequestered in organelles or intracellular compartments. RNA-seq generated reads for at least 386 annotated miRNAs, but only miR148a, miR532-5p, miR378, and let-7f were enriched in EVs compared to MSCs. Gene ontology analysis indicates that these miRNA target transcription factors and genes that participate in several cellular pathways, including angiogenesis, cellular transport, apoptosis, and proteolysis. Our data suggest that EVs transport gene regulatory information to modulate angiogenesis, adipogenesis, and other cell pathways in recipient cells. These observations may contribute to development of regenerative strategies using EVs to overcome potential complications of cell-based therapy.

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“…It has been reported that MSCs could be induced to express enhanced levels of IDO and PGE 2 . ASCs are known to constitutively produce PGE 2 and this production signi cantly increases in co-cultures [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Effect of mesenchymal stem cells combined with chondroitin sulfate in an osteoarthritis in vitro model

Pérez-Castrillo¹,

González-Fernández²,

Álvarez-Suárez³

et al. 2020

Preprint

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Introduction: Osteoarthritis (OA) is a degenerative joint disease which affects the whole joint structure. Many authors have focused on the factors responsible for the development of inflammatory processes involved in OA. Adipose tissue-derived mesenchymal stem cells (ASCs) represent a promising alternative of cell-based therapy strategy in the treatment of OA which could be combined with any other drug. Chondroitin sulfate plays a protective role in the joint based on the decrease of pro-inflammatory cytokines, thus having an important role in activating and inhibiting the metabolic pathways in chondrocytes. Aims: The effectiveness of chondroitin sulfate and ASCs combined in an in vitro model of OA has been evaluated in this study. Materials: Cytokines and factors which are involved in OA as well as specific cartilage gene expression after adding ASCs and chondroitin sulfate have been discussed in detail. Results: Our results show a decrease in the expression of all genes related to the pro-inflammatory cytokines analysed. Although there was no increase in the expression of the specific genes of the cartilage matrix, such as collagen type II and aggrecan. Conclusions: This study shows the effectiveness of association of ASCs and chondroitin sulfate for the treatment of OA.

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Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune Diseases

Cited by 27 publications

References 50 publications

Stromal Tissue Rigidity Promotes Mesenchymal Stem Cell-Mediated Corneal Wound Healing Through the Transforming Growth Factor β Signaling Pathway

Stromal Tissue Rigidity Promotes Mesenchymal Stem Cell-Mediated Corneal Wound Healing Through the Transforming Growth Factor β Signaling Pathway

MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells

Effect of mesenchymal stem cells combined with chondroitin sulfate in an osteoarthritis in vitro model

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