Co-culture with TM4 cells enhances the proliferation and migration of rat adipose-derived mesenchymal stem cells with high stemness

Luo, Yanxia; Mohsin, Ali; Xu, Chenze; Wang, Qizheng; Hang, Haifeng; Zhuang, Yingping; Chu, Ju; Guo, Meijin

doi:10.1007/s10616-018-0235-3

Cited by 12 publications

(9 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MAPKs are important mediators playing a pivotal role in cellular differentiation, proliferation, and survival, including the JNK, extracellular signal-regulating kinase1/2 (ERK1/2 or p44/42 MAPK) and p38 MAPK [[39], [40], [41], [42]]. In the present study, we found enhanced levels of JNK phosphorylation after treatment of IEC with AOPPs.…”

Section: Discussionsupporting

confidence: 57%

Advanced oxidation protein products induce G1 phase arrest in intestinal epithelial cells via a RAGE/CD36-JNK-p27kip1 mediated pathway

et al. 2019

View full text Add to dashboard Cite

Intestinal epithelial cell (IEC) cycle arrest has recently been found to be involved in the pathogenesis of Crohn's disease (CD). However, the mechanism underlying the regulation of this form of cell cycle arrest, remains unclear. Here, we investigated the roles that advanced oxidation protein products (AOPPs) may play in regulating IEC cycle arrest. Plasma AOPPs levels and IEC cycle distributions were evaluated in 12 patients with CD. Molecular changes in various cyclins, cyclin-dependent kinases (CDKs), and other regulatory molecules were examined in cultured immortalized rat intestinal epithelial (IEC-6) cells after treatment with AOPPs. The in vivo effects exerted by AOPPs were evaluated using a normal C57BL/6 mouse model with an acute AOPPs challenge. Interestingly, plasma AOPPs levels were elevated in active CD patients and correlated with IEC G1 phase arrest. In addition, IEC treatment with AOPPs markedly reduced the expression of cyclin E and CDK2, thus sensitizing epithelial cells to cell cycle arrest both in vitro and in vivo. Importantly, we found that AOPPs induced IEC G1 phase arrest by modulating two membrane receptors, RAGE and CD36. Furthermore, phosphorylation of c-jun N-terminal kinase (JNK) and the expression of p27kip1 in AOPPs-treated cells were subsequently increased and thus affected cell cycle progression. Our findings reveal that AOPPs influence IEC cycle progression by reducing cyclin E and CDK2 expression through RAGE/CD36-depedent JNK/p27kip1 signaling. Consequently, AOPPs may represent a potential therapeutic molecule. Targeting AOPPs may offer a novel approach to managing CD.

show abstract

Section: Discussionsupporting

confidence: 57%

Advanced oxidation protein products induce G1 phase arrest in intestinal epithelial cells via a RAGE/CD36-JNK-p27kip1 mediated pathway

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Sertoli cells are found in the testes and are generally thought of as “nurse cells” to developing germ cells. Coculturing MSCs with Sertoli cells upregulates proliferation genes as well as homing genes in the former, including CXCR4 (Zhang et al., 2012) and MMP-2 (Luo et al., 2018). Coculture of amniotic MSCs with amniotic epithelial cells enhances proliferation and upregulates CXCR4 (Ran et al., 2018).…”

Section: In Vitro Primingmentioning

confidence: 99%

Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement

2019

View full text Add to dashboard Cite

Mesenchymal stromal cells (MSCs) have been widely investigated for their therapeutic potential in regenerative medicine, owing to their ability to home damaged tissue and serve as a reservoir of growth factors and regenerative molecules. As such, clinical applications of MSCs are reliant on these cells successfully migrating to the desired tissue following their administration. Unfortunately, MSC homing is inefficient, with only a small percentage of cells reaching the target tissue following systemic administration. This attrition represents a major bottleneck in realizing the full therapeutic potential of MSC-based therapies. Accordingly, a variety of strategies have been employed in the hope of improving this process. Here, we review the molecular mechanisms underlying MSC homing, based on a multistep model involving (1) initial tethering by selectins, (2) activation by cytokines, (3) arrest by integrins, (4) diapedesis or transmigration using matrix remodelers, and (5) extravascular migration toward chemokine gradients. We then review the various strategies that have been investigated for improving MSC homing, including genetic modification, cell surface engineering, in vitro priming of MSCs, and in particular, ultrasound techniques, which have recently gained significant interest. Contextualizing these strategies within the multistep homing model emphasizes that our ability to optimize this process hinges on our understanding of its molecular mechanisms. Moving forward, it is only with a combined effort of basic biology and translational work that the potential of MSC-based therapies can be realized.

show abstract

“…Furthermore, activated AKT regulates cell function by phosphorylating various enzymes, kinases, transcription factors, and other factors. The AKT signaling pathway play critical role for MSCs proliferation [ 27 , 59 ], apoptosis [ 60 ], migration [ 61 ], and differentiation [ 62 ]. However, as far as we know, for the first time, we indicated that JAK2-STAT3 and AKT signaling pathway play a positive role for improving the generation of MGLCs during co-culturing of ADMSCs with SCs.…”

Section: Discussionmentioning

confidence: 99%

“…ADMSCs were isolated from 3-week male Sprague-Dawley (SD) rats and were identified to have osteogenic and adipogenic differentiation potential [ 27 ]. Passage-3 (P3) ADMSCs were used in the experiments.…”

Section: Methodsmentioning

confidence: 99%

Efficient generation of male germ-like cells derived during co-culturing of adipose-derived mesenchymal stem cells with Sertoli cells under retinoic acid and testosterone induction

et al. 2019

Self Cite

View full text Add to dashboard Cite

BackgroundAdipose-derived mesenchymal stem cells (ADMSCs) are considered an efficient and important candidate for male infertility treatment because they contain pluripotent stem cells, which can differentiate into all cells from three germ layers. However, the efficient generation of male germ-like cell (MGLCs) is one of the key issues, and little is known about the mechanisms underlying generation of MGLCs. Herein, we attempt to improve the efficient generation of MGLCs derived during co-culturing of rat ADMSCs with SCs under retinoic acid (RA) and testosterone (T) treatment.MethodsADMSCs isolated from male SD rat were induced into generation of MGLCs by using respective methods in vitro. Transwell insert system was used for co-culturing. Busulfan-induced non-obstructive azoospermia rat mode was used to evaluate spermatogenic recovery ability of treated ADMSCs. Besides, the relative gene expression level was detected by reverse transcription PCR, quantitative RT-PCR. The relative protein expression level was detected by western blot (WB) and immunostaining analysis.ResultsThe results showed that ADMSCs co-cultured with TM4 cells under RA and T induction enhanced the formation of bigger and tightly packed MGLCs feature colonies in vitro. Moreover, the expression of male germ cell-related markers (Oct4, Stella, Ddx4, Dazl, PGP9.5, Stra8, and ITGα6) is significantly upregulated in TM4 cell-co-cultured ADMSCs in vitro and in busulfan-treated rat testis after injecting TM4 cell-treated ADMSCs for 2 months. Comparatively, the ADMSCs treated by TM4 cell with RA and T exhibited the highest expression of male germ cell-related markers. RA- and T-treated TM4 cell showed fewer dead cells and higher cytokine secretion than untreated groups. The protein expression level of TGFβ-SMAD2/3, JAK2-STAT3, and AKT pathways in ADMSCs co-cultured with TM4 cells under RA and T was higher than others. Whereas, downregulation of male germ cell-related marker expression subsequently inhibited the phosphorylation of SMAD2/3, JAK2, STAT3, and AKT.ConclusionThese results suggested that TM4 cells could efficiently stimulate in vitro generation of MGLCs during co-culturing of ADMSCs under RA and T treatment. Conclusively, the ADMSCs co-cultured with TM4 cell under RA and T induction stimulate the efficient generation of MGLCs in vitro through activating TGFβ-SMAD2/3, JAK2-STAT3, and AKT pathways. Among them, JAK2-STAT3 and AKT pathways are being first reported to show involvement of in vitro generation of MGLCs during ADMSC co-culturing with SCs.Electronic supplementary materialThe online version of this article (10.1186/s13287-019-1181-5) contains supplementary material, which is available to authorized users.

show abstract

Co-culture with TM4 cells enhances the proliferation and migration of rat adipose-derived mesenchymal stem cells with high stemness

Cited by 12 publications

References 47 publications

Advanced oxidation protein products induce G1 phase arrest in intestinal epithelial cells via a RAGE/CD36-JNK-p27kip1 mediated pathway

Advanced oxidation protein products induce G1 phase arrest in intestinal epithelial cells via a RAGE/CD36-JNK-p27kip1 mediated pathway

Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement

Efficient generation of male germ-like cells derived during co-culturing of adipose-derived mesenchymal stem cells with Sertoli cells under retinoic acid and testosterone induction

Contact Info

Product

Resources

About