Modelling of the SDF-1/CXCR4 regulated <i>in vivo</i> homing of therapeutic mesenchymal stem/stromal cells in mice

Jin, Wang; Liang, Xiaowen; Brooks, Anastasia; Futrega, Kathryn; Liu, Xin; Doran, Michael; Simpson, Matthew J.; Roberts, Michael S.; Wang, Haolu

doi:10.7287/peerj.preprints.27144v1

Cited by 14 publications

(15 citation statements)

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“…The Hippo/TAZ signaling pathway can induce α-smooth muscle actin and CTGF expression that regulates epithelial-mesenchymal transition and fibrosis during tissue repair [40][41][42]. Generally, the SDF-1/CXCR4 axis is related to stem cell migration [43]. Specifically, CXCR4 and SDF-1 that were released from the injured endometrium regulate the paracrine function and regeneration of BMSCs in the injured endometrium [20].…”

Section: Discussionmentioning

confidence: 99%

Collagen Scaffold with Human Umbilical Cord Mesenchymal Stem Cells Remarkably Improves Intrauterine Adhesions in a Rat Model

Liu

Cai

Wen

et al. 2020

Gynecol Obstet Invest

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Background: Intrauterine adhesion (IUA) is the second leading cause of secondary infertility in women. Research has shown that stem cells can promote endometrial regeneration and that biomaterials are also helpful in tissue regeneration. Therefore, we compared the efficacy of a collagen scaffold combined with either human umbilical cord mesenchymal stem cells (hUCMSC) or estrogen for the treatment of IUA. Methods: The IUA-induced rats were injected with hUCMSCs or estrogen, and with a collagen scaffold. The endometrial glands and amount of fibrosis were assessed using hematoxylin and eosin and Masson staining. The extent of fibrosis and levels of regeneration-related cytokines were examined by real-time quantitative PCR, and the expression levels of the estrogen receptor, KI67 and cytokeratin were analyzed using an immunochemistry assay. In addition, human nuclear antigen (HuNu) and vimentin were examined by immunofluorescence microscopy. Results: The collagen scaffold administered with hUCMSCs markedly increased the number of endometrial glands and reduced the area of fibrosis compared with either the collagen scaffold or hUCMSCs alone. In addition, the collagen scaffold with hUCMSCs significantly regulated the expression levels of fibrosis, estrogen, and differentiation-related genes relative to the collagen scaffold or hUCMSCs alone. Furthermore, the hUCMSCs alone or in combination with the collagen scaffold increased the expression of HuNu and vimentin in the IUA-induced rat model. In addition, protein levels of the p-transcriptional co-activator with PDZ-binding motif, stromal cell-derived factor-1, and C-X-C chemokine receptor type 4 were upregulated in the group that received the collagen scaffold in combination with hUCMSCs. Conclusion: Our results suggest that the combination of the collagen scaffold with hUCMSCs may be an alternative approach for treating IUA.

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Section: Discussionmentioning

confidence: 99%

Collagen Scaffold with Human Umbilical Cord Mesenchymal Stem Cells Remarkably Improves Intrauterine Adhesions in a Rat Model

Liu

Cai

Wen

et al. 2020

Gynecol Obstet Invest

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“…The importance of the SDF‐1/CXCR4 axis in CD34 + cells homing and engraftment is unquestionable but is generally considered only in the most important direction, which is the interaction between SDF‐1 expressed in MSC and CXCR4 expressed in CD34 + cells. However, MSC can also express low levels of CXCR4 , so the fact that CD34 + cells express SDF‐1 could also potentially favors the interaction between SDF‐1 and CXCR4, enhancing the engraftment ability of CD34 + cells. We have also found an increased expression of PTGS1, precursor of PGE 2 after the incorporation of MSC‐EV.…”

Section: Discussionmentioning

confidence: 99%

The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability

et al. 2019

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Mesenchymal stromal cells (MSC) may exert their functions by the release of extracellular vesicles (EV). Our aim was to analyze changes induced in CD34 + cells after the incorporation of MSC-EV. MSC-EV were characterized by flow cytometry (FC), Western blot, electron microscopy, and nanoparticle tracking analysis. EV incorporation into CD34 + cells was confirmed by FC and confocal microscopy, and then reverse transcription polymerase chain reaction and arrays were performed in modified CD34 + cells. Apoptosis and cell cycle were also evaluated by FC, phosphorylation of signal activator of transcription 5 (STAT5) by WES Simple, and clonal growth by clonogenic assays. Human engraftment was analyzed 4 weeks after CD34 + cell transplantation in nonobese diabetic/severe combined immunodeficient mice. Our results showed that MSC-EV incorporation induced a downregulation of proapoptotic genes, an overexpression of genes involved in colony formation, and an activation of the Janus kinase (JAK)-STAT pathway in CD34 + cells. A significant decrease in apoptosis and an increased CD44 expression were confirmed by FC, and increased levels of phospho-STAT5 were confirmed by WES Simple in CD34 + cells with MSC-EV. In addition, these cells displayed a higher colony-forming unit granulocyte/macrophage clonogenic potential. Finally, the in vivo bone marrow lodging ability of human CD34 + cells with MSC-EV was significantly increased in the injected femurs. In summary, the incorporation of MSC-EV induces genomic and functional changes in CD34 + cells, increasing their clonogenic capacity and their bone marrow lodging ability. STEM CELLS 2019;37:1357-1368 SIGNIFICANCE STATEMENTIn the current study, the authors validate for the first time that preincubating human CD34 + cells with extracellular vesicles derived from human mesenchymal stromal cells not only modifies the gene expression of the recipient cells (inducing a downregulation of proapoptotic genes and overexpression of genes involved in colony formation and JAK-STAT pathway) but also significantly increases their in vitro clonogenic ability and, most importantly, increases their 4-week bone marrow lodging ability in vivo in a standard xenotransplantation model. This strategy could potentially be exploited to increase the hematopoietic engraftment in the clinical setting.

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“…, 9. Equation (10) measures the difference between the model predictions and experimental data, both scaled by the maximum value in the experimental observations. This approach of scaling normalises the two different types of the data so that both of them are in the same order of magnitude.…”

Section: Calibrating the Cell Diffusivity And The Cell Proliferation mentioning

confidence: 99%

“…Mathematical models have been applied to mimic both in vitro and in vivo experiments to test biological hypotheses and to predict experimental outcomes (Jin et al, 2018a;Jove et al, 2019;Nardini et al, 2016;Sheardown and Cheng, 1996;Tam et al, 2019;Villella et al, 2019). One of the most commonly used models to study collective cell migration is the Fisher-Kolmogorov model (Fisher, 1937;Maini et al, 2004;Sherratt and Murray, 1990;Simpson et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Quantifying the role of different surface coatings in experimental models of wound healing

Wang

Sun

et al. 2020

Chemical Engineering Science

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In vitro surface coatings are widely used to mimic the role of extracellular matrix in the in vivo environment. Different effects are reported for different surface coatings, however, some of these results are inconsistent across the literature. To explore the role of different surface coatings, we use a new modified stopper-based wound-healing assay, called a stopper assay, with two commonly used surface coatings: gelatin and poly-L-lysine (PLL). Our experimental data show the gap width decreases faster with the gelatin and PLL coatings. Similarly, the number of cells in certain subregions increases faster with these coatings. Unfortunately, neither of these observations provides definitive mechanistic insight into the role of the coatings. To provide such insight we calibrate the solution of the Fisher-Kolmogorov model to match the experimental data. Our parameter estimates indicate that both coatings significantly increase cell motility without affecting cell proliferation.

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Modelling of the SDF-1/CXCR4 regulated in vivo homing of therapeutic mesenchymal stem/stromal cells in mice

Cited by 14 publications

References 0 publications

Collagen Scaffold with Human Umbilical Cord Mesenchymal Stem Cells Remarkably Improves Intrauterine Adhesions in a Rat Model

Collagen Scaffold with Human Umbilical Cord Mesenchymal Stem Cells Remarkably Improves Intrauterine Adhesions in a Rat Model

The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability

Quantifying the role of different surface coatings in experimental models of wound healing

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