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: 9.67). 05/2010; 107(19):8639-43. DOI: 10.1073/pnas.0911647107
Source: PubMed


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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    • "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 06/2015; 2015. DOI:10.1155/2015/575837 · 3.17 Impact Factor
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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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    • "Several immunophenotypes from various human and mouse stromal cell preparations have been studied in an attempt to identify functionally relevant cell subsets and their progenitors. CD146/MCAM [10], CD271/Low affinity NGFR [11], mKirrel3 [12] and CD105+/SSEA3+ (Muse cells) [13] were proposed as cell surface marker molecules for the relevant human population. CD105+/CD90- cells [14], Nestin+ cells [15], CXCL12/SDF1+ cells (CAR cells) [16], Mx1+ cells [17], NG/CSPG4+ cells [18], LepR+ cells [19], and ENPEP+ cells [20] were reported as mouse stromal cells that help maintain hematopoiesis. "
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    ABSTRACT: In vitro expanded bone marrow stromal cells contain at least two populations of fibroblasts, a CD146/MCAM positive population, previously reported to be critical for establishing the stem cell niche and a CD146-negative population that expresses CUB domain-containing protein 1 (CDCP1)/CD318. Immunohistochemistry of marrow biopsies shows that clusters of CDCP1+ cells are present in discrete areas distinct from areas of fibroblasts expressing CD146. Using a stromal cell line, HS5, which approximates primary CDCP1+ stromal cells, we show that binding of an activating antibody against CDCP1 results in tyrosine-phosphorylation of CDCP1, paralleled by phosphorylation of Src Family Kinases (SFKs) Protein Kinase C delta (PKC-δ). When CDCP1 expression is knocked-down by siRNA, the expression and secretion of myelopoietic cytokines is increased. These data suggest CDCP1 expression can be used to identify a subset of marrow fibroblasts functionally distinct from CD146+ fibroblasts. Furthermore the CDCP1 protein may contribute to the defining function of these cells by regulating cytokine expression.
    PLoS ONE 10/2014; 9(10):e109304. DOI:10.1371/journal.pone.0109304 · 3.23 Impact Factor
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