Estrogen Secreted by Mesenchymal Stem Cells Necessarily Determines Their Feasibility of Therapeutical Application

Li, Jiansha; Peng, Xiaochun; Zeng, Xianqin; Liu, Bingxun; Hao, Qiang; Yu, Xiangyuan; Zhu, Liping; Hu, Qinghua

doi:10.1038/srep15286

Cited by 15 publications

(17 citation statements)

References 40 publications

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“…This is likely mediated by the differential expression of genes in response to injury between the two sexes; with males up-regulating pro-inflammatory pathways [ 52 ]. We postulate that male animals benefited more from female MSC as a consequence of the differential gene expression in response to lung injury between the two sexes [ 52 ], and the potential effect of estradiol (E2) secreted by female MSC on the male recipient [ 53 ]. E2 has been shown to increase the efficacy of male MSC in other models of injury [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal Hyperoxia-Induced Lung Injury

et al. 2016

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BackgroundMesenchymal stem cells (MSC) improve alveolar and vascular structures in experimental models of bronchopulmonary dysplasia (BPD). Female MSC secrete more anti-inflammatory and pro-angiogenic factors as compared to male MSC. Whether the therapeutic efficacy of MSC in attenuating lung injury in an experimental model of BPD is influenced by the sex of the donor MSC or recipient is unknown. Here we tested the hypothesis that female MSC would have greater lung regenerative properties than male MSC in experimental BPD and this benefit would be more evident in males.ObjectiveTo determine whether intra-tracheal (IT) administration of female MSC to neonatal rats with experimental BPD has more beneficial reparative effects as compared to IT male MSC.MethodsNewborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal day (P) 2- P21 were randomly assigned to receive male or female IT bone marrow (BM)-derived green fluorescent protein (GFP+) MSC (1 x 106 cells/50 μl), or Placebo on P7. Pulmonary hypertension (PH), vascular remodeling, alveolarization, and angiogenesis were assessed at P21. PH was determined by measuring right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling was evaluated by quantifying the percentage of muscularized peripheral pulmonary vessels. Alveolarization was evaluated by measuring mean linear intercept (MLI) and radial alveolar count (RAC). Angiogenesis was determined by measuring vascular density. Data are expressed as mean ± SD, and analyzed by ANOVA.ResultsThere were no significant differences in the RA groups. Exposure to hyperoxia resulted in a decrease in vascular density and RAC, with a significant increase in MLI, RVSP, and the percentage of partially and fully muscularized pulmonary arterioles. Administration of both male and female MSC significantly improved vascular density, alveolarization, RVSP, percent of muscularized vessels and alveolarization. Interestingly, the improvement in PH and vascular remodeling was more robust in the hyperoxic rodents who received MSC from female donors. In keeping with our hypothesis, male animals receiving female MSC, had a greater improvement in vascular remodeling. This was accompanied by a more significant decrease in lung pro-inflammatory markers and a larger increase in anti-inflammatory and pro-angiogenic markers in male rodents that received female MSC. There were no significant differences in MSC engraftment among groups.ConclusionsFemale BM-derived MSC have greater therapeutic efficacy than male MSC in reducing neonatal hyperoxia-induced lung inflammation and vascular remodeling. Furthermore, the beneficial effects of female MSC were more pronounced in male animals. Together, these findings suggest that female MSC maybe the most potent BM-derived MSC population for lung repair in severe BPD complicated by PH.

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Section: Discussionmentioning

confidence: 99%

The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal Hyperoxia-Induced Lung Injury

et al. 2016

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“…To determine the binding of monocrotaline to CaSR in cultured PAECs, immunocytochemical staining was performed, as reported previously . Briefly, the PAECs cultured on coverslips were rinsed with warm PBS 3 times, fixed with 4% paraformaldehyde for 20 minutes at room temperature, and rinsed again with PBS 3 times.…”

Section: Methodsmentioning

confidence: 99%

“…8 To determine the binding of monocrotaline to CaSR in cultured PAECs, immunocytochemical staining was performed, as reported previously. 8,18,20 Briefly, the PAECs cultured on coverslips were rinsed with warm PBS 3 times, fixed with 4% paraformaldehyde for 20 minutes at room temperature, and rinsed again with PBS 3 times. After blocking with 5% BSA in a humidified chamber at room temperature overnight and draining off the blocking buffer, the PAECs were incubated with primary monoclonal antibody against CaSR (1:100 diluted in 0.5% BSA in PBS; ABclonal) in a humidified chamber at 4°C overnight.…”

Section: Western Blot and Immunocytochemical Stainingmentioning

confidence: 99%

Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium–Sensing Receptor

Xiao

Tian

et al. 2017

JAHA

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BackgroundMonocrotaline has been widely used to establish an animal model of pulmonary hypertension. The molecular target underlying monocrotaline‐induced pulmonary artery endothelial injury and pulmonary hypertension remains unknown. The extracellular calcium–sensing receptor (CaSR) and particularly its extracellular domain hold the potential structural basis for monocrotaline to bind. This study aimed to reveal whether monocrotaline induces pulmonary hypertension by targeting the CaSR.Methods and ResultsNuclear magnetic resonance screening through WaterLOGSY (water ligand‐observed gradient spectroscopy) and saturation transfer difference on protein preparation demonstrated the binding of monocrotaline to the CaSR. Immunocytochemical staining showed colocalization of monocrotaline with the CaSR in cultured pulmonary artery endothelial cells. Cellular thermal shift assay further verified the binding of monocrotaline to the CaSR in pulmonary arteries from monocrotaline‐injected rats. Monocrotaline enhanced the assembly of CaSR, triggered the mobilization of calcium signaling, and damaged pulmonary artery endothelial cells in a CaSR‐dependent manner. Finally, monocrotaline‐induced pulmonary hypertension in rats was significantly attenuated or abolished by the inhibitor, the general or lung knockdown or knockout of CaSR.ConclusionsMonocrotaline aggregates on and activates the CaSR of pulmonary artery endothelial cells to trigger endothelial damage and, ultimately, induces pulmonary hypertension.

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“…14 Culture conditions are thought to be the most essential factor affecting IVM efficacy. 20 In this regard, previously, the impact of MSC-conditioned media (MSC-CM) on IVM of normal mice oocytes was demonstrated. 14 Recently, mesenchymal stromal cells (MSCs) have been considered as an ideal candidate in regenerative medicine because of their simple isolation techniques and easy expandability.…”

Section: Introductionmentioning

confidence: 97%

“…[14][15][16] On the other hand, because the efficient maturation and fertilization rate of in vitro matured oocytes is not sufficient, clinical applications of the IVM faces limitations. 20,21 MSCs secrete a variety of cytokines and growth factors, such as insulin-like growth factor-1 (IGF-1), VEGF, EGF, fibroblast growth factor (FGF), interleukin-6, leukemia inhibitory factor (LIF), TGF-β, and so on. Consequently, most IVF clinics are looking for more effective solutions to improve the developmental competency of immature oocytes.…”

Section: Introductionmentioning

confidence: 99%

Improvement of oocyte in vitro maturation from mice with polycystic ovary syndrome by human mesenchymal stromal cell–conditioned media

Jafarzadeh

Nazarian

Novin

et al. 2018

J of Cellular Biochemistry

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The outcome of in vitro maturation (IVM) in the patients with polycystic ovary syndrome (PCOS) is poor. Abnormal intraovarian paracrine interplay alters microenvironment for oocyte development through folliculogenesis and decreases developmental competence of oocytes in patients with PCOS. Mesenchymal stromal cells (MSCs) secrete a variety of cytokines and growth factors that could promote oocyte maturation in vitro. Thus, in the current study we aimed to evaluate the effect of human bone marrow MSC-conditioned media (hBM-MSC-CM), as a supplement, to enrich IVM medium for PCOS germinal vesicles (GVs). For this purpose, oocytes at GV and metaphase II (MII) stages were harvested from PCOS mice. The GVs were randomly divided into four groups and incubated for 24 hours in an IVM medium (TCM199, as the control group) or TCM199 supplemented by 25%, 50%, and 75% of hBM-MSC-CM (PCOS-CM25, PCOS-CM50, and PCOS-CM75 groups, respectively) so as to evaluate which dose(s) could enhance maturation rate of the GVs and their subsequent in vitro fertilization (IVF) outcome. Furthermore, MII oocytes and their subsequent IVF outcome were considered as the in vivo matured (PCOS-IVO) group. The data showed that supplementation of IVM medium with 50% hBM-MSC-CM significantly increased cytoplasmic and nuclear maturation of the GVs (P < 0.001), and also fertilization and two-cell rate (P < 0.001) and blastocyst formation (P < 0.01) of in vitro matured oocytes from mice with PCOS. Overall, higher oocyte maturation and fertilization outcome in PCOS-CM50 group proposed that enrichment of IVM medium with hBM-MSC-CM could be considered as a promising approach to improve IVM of PCOS oocytes.

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Estrogen Secreted by Mesenchymal Stem Cells Necessarily Determines Their Feasibility of Therapeutical Application

Cited by 15 publications

References 40 publications

The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal Hyperoxia-Induced Lung Injury

The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal Hyperoxia-Induced Lung Injury

Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium–Sensing Receptor

Improvement of oocyte in vitro maturation from mice with polycystic ovary syndrome by human mesenchymal stromal cell–conditioned media

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