Hui Wang1, Yuan Tian2, Xin Li2, Meijia Yang3, Ying Yan4,2. 1. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention Beijing, China. 2. Stem Cell and Regenerative Medicine Institute, Zhangjian Medical Group Beijing, China. 3. Boston 3T Biotechnologies Fall River, Massachusetts, USA. 4. Department of Molecular Biology, Shangqiu First People's Hospital Shangqiu, Henan, China.
Abstract
BACKGROUND: Cell transplantation is a promising treatment for the patients with end-stage liver diseases. Stem cells derived hepatocyte-like cells (HLCs) attenuated liver injury upon transplantation in animal models for liver fibrosis. However, only a small portion of the transplanted cells propagated in the recipient liver. AIM: We hypothesized that the efficiency of cell therapy could be improved by transplanting amniotic mesenchymal stem cells (AMSCs) derived HLCs along with human umbilical vein endothelial cells (HUVECs) and undifferentiated AMSCs. METHODS: Briefly, we used a two-step protocol to generate induced HLCs. We confirmed organoids formation of HLCs in 3D collagen scaffolds with HUVECs and AMSCs. To determine whether the HLCs can migrate into the liver tissue and perform in vivo function, we transplanted the cells to mice with liver fibrosis. RESULTS: Co-culture of HLCs with HUVECs and AMSCs demonstrated improved function of HLCs within the organoids. Furthermore, transplantation using non-homogeneous cells, i.e. HLCs mixed with HUVECs and AMSCs, exhibited better graft survival in the host animals with liver fibrosis. Our experiment results suggested that compared to mock transplantation or HLCs transplantation groups, liver fibrosis was reduced significantly in mixed-cell groups. The AST levels in the plasma of transplanted mice were markedly decreased only in the mixed-cell transplantation group. The engraftment of HLCs in mice liver was better in mixed-cell transplantation group, compared with HLCs-only transplantation group. CONCLUSIONS: The HLCs attenuated liver fibrosis more efficiently when transplanted along with HUVECs and AMSCs, and this suggested that we could improve the efficiency of cell therapy by transplanting functional cells partially along with stromal cells. IJPPP
BACKGROUND: Cell transplantation is a promising treatment for the patients with end-stage liver diseases. Stem cells derived hepatocyte-like cells (HLCs) attenuated liver injury upon transplantation in animal models for liver fibrosis. However, only a small portion of the transplanted cells propagated in the recipient liver. AIM: We hypothesized that the efficiency of cell therapy could be improved by transplanting amniotic mesenchymal stem cells (AMSCs) derived HLCs along with human umbilical vein endothelial cells (HUVECs) and undifferentiated AMSCs. METHODS: Briefly, we used a two-step protocol to generate induced HLCs. We confirmed organoids formation of HLCs in 3D collagen scaffolds with HUVECs and AMSCs. To determine whether the HLCs can migrate into the liver tissue and perform in vivo function, we transplanted the cells to mice with liver fibrosis. RESULTS: Co-culture of HLCs with HUVECs and AMSCs demonstrated improved function of HLCs within the organoids. Furthermore, transplantation using non-homogeneous cells, i.e. HLCs mixed with HUVECs and AMSCs, exhibited better graft survival in the host animals with liver fibrosis. Our experiment results suggested that compared to mock transplantation or HLCs transplantation groups, liver fibrosis was reduced significantly in mixed-cell groups. The AST levels in the plasma of transplanted mice were markedly decreased only in the mixed-cell transplantation group. The engraftment of HLCs in mice liver was better in mixed-cell transplantation group, compared with HLCs-only transplantation group. CONCLUSIONS: The HLCs attenuated liver fibrosis more efficiently when transplanted along with HUVECs and AMSCs, and this suggested that we could improve the efficiency of cell therapy by transplanting functional cells partially along with stromal cells. IJPPP
Authors: Iain R Murray; Christopher C West; Winters R Hardy; Aaron W James; Tea Soon Park; Alan Nguyen; Tulyapruek Tawonsawatruk; Lorenza Lazzari; Chia Soo; Bruno Péault Journal: Cell Mol Life Sci Date: 2013-10-25 Impact factor: 9.261