Dataset Information

Predictors of responders to mononuclear stem cell-based therapeutic angiogenesis for no-option critical limb ischemia.

ABSTRACT:

Background

Although the mononuclear cell (MNC) transplantation could theoretically induce therapeutic angiogenesis in the patients with no-option critical limb ischemia (NO-CLI), the clinical responses to this approach are inconsistent among different clinical trials. The purpose of this study was to identify the prognostic factors of responders and develop a predictive nomogram to guide patient selection.

Methods

We retrospectively reviewed a consecutive NO-CLI cohort who received peripheral blood-derived transplantation in our center. The patients who survived and achieved complete remission of CLI at 6 months post-transplantation were defined as responders. Logistic regression models were used to screen and identify the prognostic factors based on which predictive nomogram was developed. A receiver operating characteristic (ROC) curve and a calibration curve were drawn to determine the discrimination level and predictive accuracy.

Results

The study ultimately enrolled 103 patients, including 58 responders and 45 non-responders. Based on the multivariate regression analysis, age ≥ 50 years (odds ratio [OR] 0.201, P = 0.004), blood fibrinogen > 4 g/L (OR 0.176, P = 0.003), arterial occlusion above the knee/elbow (OR 0.232, P = 0.010), the transcutaneous pressure of oxygen (TcPO₂) (OR 1.062, P = 0.006), and the Log total transplanted CD34⁺ cell count (OR 3.506, P = 0.046) were identified as independent prognostic factors of the responders in the nomogram. An area under the ROC curve of 0.851 indicated good discrimination, and the calibration curve of the predicted probability showed optimal agreement with that of the observed probability.

Conclusions

Age, blood fibrinogen, arterial occlusion level, TcPO₂, and the total transplanted CD34⁺ cell count were independent prognostic factors of the responders. A nomogram with high discrimination and accuracy was developed to provide individualized predictions.

Trail registration

ChiCTR, ChiCTR1800019401 . Registered 9 November 2018-Retrospectively registered.

SUBMITTER: Pan T

PROVIDER: S-EPMC6329149 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Predictors of responders to mononuclear stem cell-based therapeutic angiogenesis for no-option critical limb ischemia.

Pan Tianyue T Liu Hao H Fang Yuan Y Wei Zheng Z Gu Shiyang S Fang Gang G Liu Yifan Y Luo Yang Y Guo Daqiao D Xu Xin X Chen Bin B Jiang Junhao J Yang Jue J Shi Zhenyu Z Zhu Ting T Shi Yun Y Liu Peng P Dong Zhihui Z Fu Weiguo W

Stem cell research & therapy 20190111 1

<h4>Background</h4>Although the mononuclear cell (MNC) transplantation could theoretically induce therapeutic angiogenesis in the patients with no-option critical limb ischemia (NO-CLI), the clinical responses to this approach are inconsistent among different clinical trials. The purpose of this study was to identify the prognostic factors of responders and develop a predictive nomogram to guide patient selection.<h4>Methods</h4>We retrospectively reviewed a consecutive NO-CLI cohort who receive ...[more]

PMID: 30635050

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Project description:BackgroundVasculogenic therapies explored for the treatment of peripheral artery disease (PAD) have encountered minimal success in clinical trials. Addressing this, B55α, an isoform of protein phosphatase 2A (PP2A), emerges as pivotal in vessel remodeling through activation of hypoxia-inducible factor 1α (HIF-1α). This study delves into the pharmacological profile of VCE-004.8 (Etrinabdione) and evaluates its efficacy in a preclinical model of critical limb ischemia, with a focus on its potential as a PP2A/B55α activator to induce angiogenesis and arteriogenesis.MethodsVascular endothelial cells were used for in vitro experiments. Aorta ring assay was performed to explore sprouting activity. Matrigel plug-in assay was used to assess the angiogenic potential. Critical limb ischemia (CLI) in mice was induced by double ligation in the femoral arteria. Endothelial vascular and fibrotic biomarkers were studied by immunohistochemistry and qPCR. Arteriogenesis was investigated by microvascular casting and micro-CT. Proteomic analysis in vascular tissues was analyzed by LC-MS/MS. Ex-vivo expression of B55α and biomarkers were investigated in artery samples from PAD patients.ResultsVCE-004.8 exhibited the ability to induce B55α expression and activate the intersecting pathways B55α/AMPK/Sirtuin 1/eNOS and B55α/PHD2/HIF-1α. VCE-004.8 prevented OxLDL and H2O2-induced cytotoxicity, senescence, and inflammation in endothelial cells. Oral VCE-004.8 increased aorta sprouting in vitro and angiogenesis in vivo. In CLI mice VCE-004.8 improved collateral vessel formation and induced endothelial cells proliferation, angiogenic gene expression and prevented fibrosis. The expression of B55α, Caveolin 1 and Sirtuin-1 is reduced in arteries from CLI mice and PAD patient, and the expression of these markers was restored in mice treated with VCE-004.8.ConclusionsThe findings presented in this study indicate that Etrinabdione holds promise in mitigating endothelial cell damage and senescence, while concurrently fostering arteriogenesis and angiogenesis. These observations position Etrinabdione as a compelling candidate for the treatment of PAD, and potentially other cardiovascular disorders.

Dataset Information

Predictors of responders to mononuclear stem cell-based therapeutic angiogenesis for no-option critical limb ischemia.

Background

Methods

Results

Conclusions

Trail registration

Publications

Predictors of responders to mononuclear stem cell-based therapeutic angiogenesis for no-option critical limb ischemia.

Similar Datasets

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