Very small embryonic‐like stem cells are present in adult murine organs: ImageStream‐based morphological analysis and distribution studies

Recently, we purified a population of CXCR4+/Oct‐4+/SSEA‐1+/Sca‐1+/Lin−/CD45− very small embryonic‐like stem cells (VSELs) from adult murine bone marrow (BM). After using flow cytometry, ImageStream analysis, confocal microscopy, and real time RT‐PCR, we report that similar cells could be also identified and isolated from several organs in adult mice. The highest total numbers of Oct‐4+ VSELs were found in the brain, kidneys, muscles, pancreas, and BM. These observations support our hypothesis that a population of very primitive cells expressing germ line/epiblast markers (Oct‐4, SSEA‐1) is deposited early during embryogenesis in various organs and survives into adulthood. Further studies are needed to determine whether these cells, after being isolated from various adult human organs similarly to their murine BM‐derived counterparts, are endowed with pluripotent stem cell properties. © 2008 International Society for Advancement of Cytometry

[1]  P. Schiller,et al.  Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential , 2004, Journal of Cell Science.

[2]  J. Wagner,et al.  Separation of pluripotent haematopoietic stem cells from spleen colony-forming cells , 1990, Nature.

[3]  B. Larson,et al.  Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. , 2004, Blood.

[4]  H. Kaplan,et al.  Endogenous bone marrow derived cells express retinal pigment epithelium cell markers and migrate to focal areas of RPE damage. , 2007, Investigative ophthalmology & visual science.

[5]  M. Ratajczak,et al.  “Small stem cells” in adult tissues: Very small embryonic‐like stem cells stand up! , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[6]  H. Ulrich,et al.  Novel perspectives of neural stem cell differentiation: From neurotransmitters to therapeutics , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[7]  David Basiji,et al.  Quantitative measurement of nuclear translocation events using similarity analysis of multispectral cellular images obtained in flow. , 2006, Journal of immunological methods.

[8]  M. Ratajczak,et al.  Evidence That Very Small Embryonic‐Like Stem Cells Are Mobilized into Peripheral Blood , 2008, Stem cells.

[9]  R. Bolli,et al.  Bone marrow-derived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction. , 2008, Journal of molecular and cellular cardiology.

[10]  S. Rafii,et al.  Evidence for circulating bone marrow-derived endothelial cells. , 1998, Blood.

[11]  M. Ratajczak,et al.  Stem cell plasticity revisited: CXCR4-positive cells expressing mRNA for early muscle, liver and neural cells ‘hide out’ in the bone marrow , 2004, Leukemia.

[12]  J. Paul Robinson,et al.  Automated classification of bacterial particles in flow by multiangle scatter measurement and support vector machine classifier , 2008, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[13]  Ho-Joon Lee,et al.  Oocyte Generation in Adult Mammalian Ovaries by Putative Germ Cells in Bone Marrow and Peripheral Blood , 2005, Cell.

[14]  J Ratajczak,et al.  Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells , 2005, Leukemia.

[15]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[16]  M. Ratajczak,et al.  “Small stem cells” in adult tissues: Very small embryonic‐like stem cells stand up! , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[17]  Siddhartha Sharma,et al.  Cellular volume and marker expression in human peripheral blood apheresis stem cells , 2008, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[18]  D. Prockop Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues , 1997, Science.

[19]  M. Ratajczak,et al.  A hypothesis for an embryonic origin of pluripotent Oct-4+ stem cells in adult bone marrow and other tissues , 2007, Leukemia.

[20]  David A Basiji,et al.  Distinguishing modes of cell death using the ImageStream® multispectral imaging flow cytometer , 2004, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[21]  M. Ratajczak,et al.  A multi-instrumental approach to identify and purify very small embryonic like stem cells (VSELs) from adult tissues. , 2009, Micron.

[22]  David A Basiji,et al.  Sensitivity measurement and compensation in spectral imaging , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[23]  James W Lillard,et al.  Morphological characterization of very small embryonic-like stem cells (VSELs) by ImageStream system analysis , 2007, Journal of cellular and molecular medicine.

[24]  J Ratajczak,et al.  A population of very small embryonic-like (VSEL) CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow , 2006, Leukemia.

[25]  C. Vacanti,et al.  Identification and initial characterization of spore‐like cells in adult mammals , 2001, Journal of cellular biochemistry.

[26]  W. Engel,et al.  Derivation of male germ cells from bone marrow stem cells , 2006, Laboratory Investigation.

[27]  Catherine M. Verfaillie,et al.  Pluripotency of mesenchymal stem cells derived from adult marrow , 2007, Nature.

[28]  M. Ratajczak,et al.  Bone marrow‐derived very small embryonic‐like stem cells: Their developmental origin and biological significance , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[29]  P. Morrison,et al.  Pluripotent Stem Cells Identified in Multiple Murine Tissues , 2003, Annals of the New York Academy of Sciences.