Human Amniotic Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells May Generate a Universal Source of Cardiac Cells

1 Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California.
Stem cells and development (Impact Factor: 3.73). 04/2012; 21(15):2798-808. DOI: 10.1089/scd.2011.0435
Source: PubMed


Human amniotic mesenchymal stem cells (hAMSCs) demonstrated partially pluripotent characteristics with a strong expression of Oct4 and Nanog genes and immunomodulatory properties characterized by the absence of HLA-DR and the presence of HLA-G and CD59. The hAMSCs were reprogrammed into induced pluripotent stem cells (iPSCs) that generate a promising source of universal cardiac cells. The hAMSC-derived iPSCs (MiPSCs) successfully underwent robust cardiac differentiation to generate cardiomyocytes. This study investigated 3 key properties of the hAMSCs and MiPSCs: (1) the reprogramming efficiency of the partially pluripotent hAMSCs to generate MiPSCs; (2) immunomodulatory properties of the hAMSCs and MiPSCs; and (3) the cardiac differentiation potential of the MiPSCs. The characteristic iPSC colony formation was observed within 10 days after the transduction of the hAMSCs with a single integration polycistronic vector containing 4 Yamanaka factors. Immunohistology and reverse transcription-polymerase chain reaction assays revealed that the MiPSCs expressed stem cell surface markers and pluripotency-specific genes. Furthermore, the hAMSCs and MiPSCs demonstrated immunomodulatory properties enabling successful engraftment in the SVJ mice. Finally, the cardiac differentiation of MiPSCs exhibited robust spontaneous contractility, characteristic calcium transience across the membrane, a high expression of cardiac genes and mature cardiac phenotypes, and a contractile force comparable to cardiomyocytes. Our results demonstrated that the hAMSCs are reprogrammed with a high efficiency into MiPSCs, which possess pluripotent, immunomodulatory, and precardiac properties. The MiPSC-derived cardiac cells express a c-kit cell surface marker, which may be employed to purify the cardiac cell population and enable allogeneic cardiac stem cell therapy.

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Available from: Renee A Reijo Pera, Jul 07, 2015
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    • "Recently, several ASCs have been successfully isolated and cultured in vitro, including hematopoietic stem cells (HSCs)11, mesenchymal stem cells (MSCs)1213, epidermis stem cells14, neural stem cells (NSCs)15, adipose-derived stem cells (ADSCs)161718, islet stem cells1920, and germ line stem cells212223. Human mesenchymal stem cells originate mainly from bone marrow2425, cord blood262728, placenta293031, and endometrium32, but epidermis-derived MSCs have not yet been isolated. In the present study, we isolated small spindle-shaped cells with strong proliferative potential from human epidermis. "
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    Scientific Reports 06/2013; 3:1933. DOI:10.1038/srep01933 · 5.58 Impact Factor
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    • "Human amniocytes are considered an embryonic or fetal multipotent stem cell due to expression of transcriptional regulators [11]–[14] and cell surface antigens [15]–[18] characteristic of stem cells. Interestingly, amniocytes can be efficiently reprogrammed into a primitive pluripotent state by DNA-integrating [19]–[25] and non-integrating methods [18], and subsequently differentiated along multiple lineages [17], [18], [22], [26]–[32]. Alternatively, they can be reprogrammed through direct methods, which are thought to bypass pluripotency altogether [33], or as our data suggests, use some of the innate pluripotency of amniocytes. "
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