Unique multipotent cells in adult human mesenchymal cell populations

Department of Stem Cell Biology and Histology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 05/2010; 107(19):8639-43. DOI: 10.1073/pnas.0911647107
Source: PubMed

ABSTRACT We found adult human stem cells that can generate, from a single cell, cells with the characteristics of the three germ layers. The cells are stress-tolerant and can be isolated from cultured skin fibroblasts or bone marrow stromal cells, or directly from bone marrow aspirates. These cells can self-renew; form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency; and can differentiate into endodermal, ectodermal, and mesodermal cells both in vitro and in vivo. When transplanted into immunodeficient mice by local or i.v. injection, the cells integrated into damaged skin, muscle, or liver and differentiated into cytokeratin 14-, dystrophin-, or albumin-positive cells in the respective tissues. Furthermore, they can be efficiently isolated as SSEA-3(+) cells. Unlike authentic ES cells, their proliferation activity is not very high and they do not form teratomas in immunodeficient mouse testes. Thus, nontumorigenic stem cells with the ability to generate the multiple cell types of the three germ layers can be obtained through easily accessible adult human mesenchymal cells without introducing exogenous genes. These unique cells will be beneficial for cell-based therapy and biomedical research.

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Available from: Akira Niwa, Oct 09, 2014
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    • "It was later proven that only real adult stem cells (muse cells) can generate those claimed induced pluripotent stem cells [5] [6] . "
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    ABSTRACT: The claimed human induced pluripotent stem cells (iPSCs) are not equivalent to human embryonic or adult stem cells. These should be redefined as induced pluripotent stem cell-like cells. We do not think that those so-called induced pluripotent stem cells will be a reliable and feasible source of stem cells for the foreseeable future.
    01/2015; 29(1):1-2. DOI:10.7555/JBR.29.20140166
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    • "However, the superiority of this method over the use of unfractionated cells in terms of the number and/or functionality of the generated IPCs was not provided. Recently, Kuroda and colleagues isolated what they defined as multilineage differentiating stress-enduring (Muse) cells cultured from skin fibroblasts or bone marrow stromal cells [40]. These cells were positive for both CD105, a mesenchymal cell marker, and SSEA-3, a human pluripotency marker. "
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    ABSTRACT: Th aim of this study was to provide evidence for further in vivo maturation of insulin-producing cells (IPCs) derived from human bone marrow-derived mesenchymal stem cells (HBM-MSCs). HBM-MSCs were obtained from three insulin-dependent type 2 diabetic volunteers. Following expansion, cells were diffrentiated according to a trichostatin-A/GLP protocol. One million cells were transplanted under the renal capsule of 29 diabetic nude mice. Blood glucose, serum human insulin and c-peptide levels, and glucose tolerance curves were determined. Mice were euthanized 1, 2, 4, or 12 weeks aftr transplantation. IPC-bearing kidneys were immunolabeled, number of IPCs was counted, and expression of relevant genes was determined. At the end of in vitro diffrentiation, all pancreatic endocrine genes were expressed, albeit at very low values. Th percentage of IPCs among transplanted cells was small (≤3%). Diabetic animals became euglycemic 8 ± 3 days aftr transplantation. Threaftr, the percentage of IPCs reached a mean of∼18% at 4 weeks. Relative gene expression of insulin, glucagon, and somatostatin showed a parallel increase. Th ability of the transplanted cells to induce euglycemia was due to their further maturation in the favorable in vivo microenvironment. Elucidation of the exact mechanism(s) involved requires further investigation.
    BioMed Research International 01/2015; 2015. DOI:10.1155/2015/575837 · 2.71 Impact Factor
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    • "BM-derived MSCs show poluripotency-differentiation properties (Kuroda et al., 2013). Interestingly, stress conditions could enrich the expression of SSEA-3 in cultured MSCs (Kuroda et al., 2010). Y. Kuroda et al. demonstrated that long-term trypsin incubation could increase the recovery of cell clusters containing pluripotency-associated markers and renamed these cells as " multi-lineage differentiating stress-enduring " (MUSE) cells. "
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    ABSTRACT: Recent investigations have made considerable progress in the understanding of tissue regeneration driven by mesenchymal stromal cells (MSCs). Data indicate the anatomical location of MSC as residing in the “perivascular” space of blood vessels dispersed across the whole body. This histological localization suggests that MSCs contribute to the formation of new blood vessels in vivo. Indeed, MSCs can release angiogenic factors and protease to facilitate blood vessel formation and in vitro are able to promote/support angiogenesis. However, the direct differentiation of MCSs into endothelial cells is still matter of debate. Most of the conflicting data might arise from the presence of multiple subtypes of cells with heterogeneous morpho functional features within the MSC cultures. According to this scenario, we hypothesize that the presence of the recently described Mesodermal Progenitor Cells (MPCs) within the MSCs cultures is responsible for their variable angiogenic potential. Indeed, MPCs are Nestin-positive CD31-positive cells exhibiting angiogenic potential that differentiate in MSC upon proper stimuli. The ISCT criteria do not account for the presence of MPC within MSC culture generating confusion in the interpretation of MSC angiogenic potential. In conclusion, the discover y of MPC gives new insight in defining MSC ancestors in human bone marrow, and indicates the tunica intima as a further, and previously overlooked, possible additional source of MSC.
    Frontiers in Cell and Developmental Biology 05/2014; 2. DOI:10.3389/fcell.2014.00020
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