Abstract
IntroductionAdipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4) in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway.MethodsADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4)-induced liver fibrosis rats. Computed tomography (CT) perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated.ResultsCT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII) immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF) was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein.ConclusionsADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.
Highlights
Adipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis
Isolation and identification of ADMSCs ADMSCs were isolated from SD rat inguinal fat pad, and proliferating cells were enriched as described before
We performed Computed tomography (CT) perfusion scan on experimental subjects to measure the alteration of liver microcirculation
Summary
Adipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4) in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway. Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to benefit in the prevention of pulmonary fibrotic lesions [5], or ameliorate changes of liver function tests in experimental fibrosis models [6]. Adipose derived mesenchymal stem cells (ADMSCs), as a source of adult mesenchymal stem cells, display similar multiple-linage differentiating potentials to bone marrow MSCs [8,9,10,11]. The yield from one gram adipose tissue is approximately 5,000 to 20,000 stem cells, whereas the yield from 1 ml BM-MSCs is only 2% to 20% of ADMSCs, which makes ADMSCs a promising alternative for cytotherapy
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