Differentiation and Transplantation of Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells

Asgari, Samira; Moslem, Mohsen; Bagheri-Lankarani, Kamran; Pournasr, Behshad; Miryounesi, Maryam; Baharvand, Hossein
August 2013
Stem Cell Reviews & Reports;Aug2013, Vol. 9 Issue 4, p493
Academic Journal
The generation of human induced pluripotent stem cells (hiPSCs) with a high differentiation potential provided a new source for hepatocyte generation not only for drug discovery and in vitro disease models, but also for cell replacement therapy. However, the reported hiPSC-derived hepatocyte-like cells (HLCs) were not well characterized and their transplantation, as the most promising clue of cell function was not reported. Here, we performed a growth factor-mediated differentiation of functional HLCs from hiPSCs and evaluated their potential for recovery of a carbon tetrachloride (CCl)-injured mouse liver following transplantation. The hiPSC-derived hepatic lineage cells expressed hepatocyte-specific markers, showed glycogen and lipid storage activity, secretion of albumin (ALB), alpha-fetoprotein (AFP), urea, and CYP450 metabolic activity in addition to low-density lipoprotein (LDL) and indocyanin green (ICG) uptake. Similar results were observed with human embryonic stem cell (hESC)-derived HLCs. The transplantation of hiPSC-HLCs into a CCl-injured liver showed incorporation of the hiPSC-HLCs into the mouse liver which resulted in a significant enhancement in total serum ALB after 1 week. A reduction of total serum LDH and bilirubin was seen when compared with the control and sham groups 1 and 5 weeks post-transplantation. Additionally, we detected human serum ALB and ALB-positive transplanted cells in both the host serum and livers, respectively, which showed functional integration of transplanted cells within the mouse livers. Therefore, our results have opened up a proof of concept that functional HLCs can be generated from hiPSCs, thus improving the general condition of a CCl-injured mouse liver after their transplantation. These results may bring new insights in the clinical applications of hiPSCs once safety issues are overcome.


Related Articles

  • High Efficient Differentiation of Functional Hepatocytes from Porcine Induced Pluripotent Stem Cells. Ao, Ying; Mich-Basso, Jocelyn Danielle; Lin, Bo; Yang, Lei // PLoS ONE;Jun2014, Vol. 9 Issue 6, p1 

    Hepatocyte transplantation is considered to be a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs) provide an unlimited source for the generation of functional hepatocytes. In this study, we generated iPSCs from porcine ear fibroblasts (PEFs) by...

  • Generation of Mouse and Human Induced Pluripotent Stem Cells (iPSC) from Primary Somatic Cells. Lorenzo, I.; Fleischer, A.; Bachiller, D. // Stem Cell Reviews & Reports;Aug2013, Vol. 9 Issue 4, p435 

    Cellular reprogramming consists of the conversion of differentiated cells into pluripotent cells; the so-called induced Pluripotent Stem Cells. iPSC are amenable to in vitro manipulation and, in theory, direct production of any differentiated cell type. Furthermore, iPSC can be obtained from...

  • Life is a continuous journey of transformation? DAMLE, S. G. // Contemporary Clinical Dentistry;Jul-Sep2013, Vol. 4 Issue 3, p277 

    The author reflects on a study which directed urine stem cells to be converted into bladder type cells such as endothelial cells and smooth muscle cells. He says that the study is based on previous research on cell multipotency as well as studies that show induced pluripotent stem cells (iPSC)...

  • Derivation of iPSCs in stirred suspension bioreactors. Shafa, Mehdi; Day, Brad; Yamashita, Akihiro; Meng, Guoliang; Liu, Shiying; Krawetz, Roman; Rancourt, Derrick E // Nature Methods;May2012, Vol. 9 Issue 5, p465 

    Induced pluripotent stem cells (iPSCs) are typically derived in adherent culture. Here we report fast and efficient derivation of mouse iPSCs in stirred suspension bioreactors, with and without the use of c-Myc. Suspension-reprogrammed cells expressed pluripotency markers, showed multilineage...

  • Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Abad, María; Mosteiro, Lluc; Pantoja, Cristina; Cañamero, Marta; Rayon, Teresa; Ors, Inmaculada; Graña, Osvaldo; Megías, Diego; Domínguez, Orlando; Martínez, Dolores; Manzanares, Miguel; Ortega, Sagrario; Serrano, Manuel // Nature;10/17/2013, Vol. 502 Issue 7471, p340 

    Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of in vivo reprogramming within tissues. Here we show that transitory induction of the four factors Oct4, Sox2, Klf4 and...

  • Deletion of Alox5 gene decreases osteogenic differentiation but increases adipogenic differentiation of mouse induced pluripotent stem cells. Wu, Yanru; Sun, Hualing; Song, Fangfang; Huang, Cui; Wang, Jiawei // Cell & Tissue Research;Oct2014, Vol. 358 Issue 1, p135 

    Induced pluripotent stem cells (iPSCs) have great potential in bone tissue engineering to repair large bone defects. Before their clinical application, investigations are needed to discover the genes and osteoconductive scaffolds that influence their differentiation toward an osteogenic lineage....

  • Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications. Tao, Hongyan; Han, Zhibo; Han, Zhong Chao; Li, Zongjin // Stem Cells International;1/6/2016, p1 

    Mesenchymal stem cells (MSCs) have shown their therapeutic potency for treatment of cardiovascular diseases owing to their low immunogenicity, ease of isolation and expansion, and multipotency. As multipotent progenitors, MSCs have revealed their ability to differentiate into various cell types...

  • Regenerative medicine: Transdifferentiation in vivo. Fu, Lina; Zhu, Xiping; Yi, Fei; Liu, Guang-Hui; Belmonte, Juan Carlos Izpisua // Cell Research;Feb2014, Vol. 24 Issue 2, p141 

    A major challenge in regenerative medicine is the generation of functionally effective target cells to replace or repair damaged tissues. Transdifferentiation in vivo is a novel strategy to achieve cell fate conversion within the native physiological niche; this technology may provide a time-...

  • Identification of small molecules for human hepatocyte expansion and iPS differentiation. Shan, Jing; Schwartz, Robert E; Ross, Nathan T; Logan, David J; Thomas, David; Duncan, Stephen A; North, Trista E; Goessling, Wolfram; Carpenter, Anne E; Bhatia, Sangeeta N // Nature Chemical Biology;Aug2013, Vol. 9 Issue 8, p514 

    Cell-based therapies hold the potential to alleviate the growing burden of liver diseases. Such therapies require human hepatocytes, which, within the stromal context of the liver, are capable of many rounds of replication. However, this ability is lost ex vivo, and human hepatocyte sourcing has...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics