Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology: Recent pros and cons in the midst of a lively debate

Leukemia

Volumn 28, Issue 3, 2014, Pages 473-484

  Ratajczak, M Z ^a   Zuba Surma, E ^b   Wojakowski, W ^c   Suszynska, M ^a   Mierzejewska, K ^d   Liu, R ^a   Ratajczak, J ^a,d   Shin, D M ^e   Kucia, M ^a,d  

^a UNIVERSITY OF LOUISVILLE   (United States)

^b JAGIELLONIAN UNIVERSITY   (Poland)

^c MEDICAL UNIVERSITY OF SILESIA   (Poland)

^d POMERANIAN MEDICAL UNIVERSITY   (Poland)

^e University of Ulsan College of Medicine   (South Korea)

Author keywords

Epiblast stem cells; Igf2 H19; Oct 4; Primordial germ cells; Sall 4; VSELs

Indexed keywords

FOLLITROPIN; INSULIN; LUTEINIZING HORMONE; SERIC GONADOTROPIN; SOMATOMEDIN;

ADULT STEM CELL; BLASTOCYST; CELL DIFFERENTIATION; CELL MATURATION; CELL POPULATION; CYTOLOGY; ECTODERM; EMBRYONIC STEM CELL; EPIGENETICS; FLUORESCENCE ACTIVATED CELL SORTING; GENE EXPRESSION; GENETIC MARKER; GENOME IMPRINTING; GERMLINE STEM CELL; HEMATOPOIETIC STEM CELL; HUMAN; INSULIN RESISTANCE; LIFESPAN; MESENCHYMAL STEM CELL; NONHUMAN; ONTOGENY; OOCYTE; PERIPHERAL BLOOD STEM CELL; PHENOTYPIC PLASTICITY; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REVIEW; SOMATIC CELL; SPERMATOZOON; TISSUE REGENERATION; VERY SMALL EMBRYONIC LIKE STEM CELL;

ANIMALS; CELL DIFFERENTIATION; EMBRYONIC STEM CELLS; EPIGENESIS, GENETIC; GENOMIC IMPRINTING; MICE;

EID: 84895803604     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2013.255     Document Type: Review

References (107)

1. Tachibana M, Amato P, Sparman M, Gutierrez NM, Tippner-Hedges R, Ma H et al. Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 2013; 153: 1228-1238.
2. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.
3. Zhao T, Zhang ZN, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature 2011; 474: 212-215.
4. Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008; 451: 141-146.
5. Lee AS, Tang C, Rao MS, Weissman IL, Wu JC. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med 2013; 19: 998-1004.
6. Ratajczak MZ, Kucia M, Jadczyk T, Greco NJ, Wojakowski W, Tendera M et al. Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: Can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies?. Leukemia 2012; 26: 1166-1173.
7. Ratajczak J, Kucia M, Mierzejewska K, Marlicz W, Pietrzkowski Z, Wojakowski W et al. Paracrine proangiopoietic effects of human umbilical cord blood-derived purified CD133þ cells - implications for stem cell therapies in regenerative medicine. Stem Cells Dev 2013; 22: 422-430.
8. Schweitzer KS, Johnstone BH, Garrison J, Rush NI, Cooper S, Traktuev DO et al. Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking. Am J Respir Crit Care Med 2011; 183: 215-225.
9. Camussi G, Deregibus MC, Tetta C. Paracrine/endocrine mechanism of stem cells on kidney repair: Role of microvesicle-mediated transfer of genetic information. Curr Opin Nephrol Hypertens 2010; 19: 7-12.
10. Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z, Kowalska MA et al. Numerous growth factors, cytokines, and chemokines are secreted by human CD34(þ) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood 2001; 97: 3075-3085.
11. Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 2002; 416: 542-545.
12. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 2003; 422: 897-901.
13. Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001; 107: 1395-1402.
14. Kucia M, Reca R, Campbell FR, Zuba-Surma E, Majka M, Ratajczak J et al. A population of very small embryonic-like (VSEL) CXCR4(þ)SSEA- 1(þ)Oct-4þ stem cells identified in adult bone marrow. Leukemia 2006; 20: 857-869.
15. Kucia M, Halasa M, Wysoczynski M, Baskiewicz-Masiuk M, Moldenhawer S, Zuba-Surma E et al. Morphological and molecular characterization of novel population of CXCR4þ SSEA-4þ Oct-4þ very small embryonic-like cells purified from human cord blood: Preliminary report. Leukemia 2007; 21: 297-303.
16. Taichman RS, Wang Z, Shiozawa Y, Jung Y, Song J, Balduino A et al. Prospective identification and skeletal localization of cells capable of multilineage differentiation in vivo. Stem Cells Dev 2010; 19: 1557-1570.
17. Kassmer SH, Jin H, Zhang PX, Bruscia EM, Heydari K, Lee JH et al. Very small embryonic-like stem cells from the murine bone marrow differentiate into epithelial cells of the lung. Stem Cells 2013, e-pub ahead of print 16 May 2013; doi:10.1002/stem.1413.
18. Havens AM, Shiozawa Y, Jung Y, Sun H, Wang J, McGee S et al. Human very small embryonic-like cells generate skeletal structures, in vivo. Stem Cells Dev 2013; 22: 622-630.
19. Parte S, Bhartiya D, Telang J, Daithankar V, Salvi V, Zaveri K et al. Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary. Stem Cells Dev 2011; 20: 1451-1464.
20. Bhartiya D, Kasiviswananthan S, Shaikh A. Cellular origin of testis-derived pluripotent stem cells: A case for very small embryonic-like stem cells. Stem Cells Dev 2012; 21: 670-674.
21. Sovalat H, Scrofani M, Eidenschenk A, Pasquet S, Rimelen V, Henon P. Identification and isolation from either adult human bone marrow or G-CSF-mobilized peripheral blood of CD34(þ)/CD133(þ)/ CXCR4(þ)/ Lin(-)CD45(-) cells, featuring morphological, molecular, and phenotypic characteristics of very small embryonic-like (VSEL) stem cells. Exp Hematol 2011; 39: 495-505.
22. Iwaki R, Nakatsuka R, Matsuoka YM, Takahashi M, Fujioka T, Sasaki Y et al. Development of a highly efficient method for isolating very small embryonic-like stem cells identified in adult mouse bone and their stem cell characteristic. ASH Annual Meeting Abstracts. Blood 2012; 120(suppl 1): 2345.
23. Halasa M, Baskiewicz-Masiuk M, Dabkowska E, Machalinski B. An efficient two-step method to purify very small embryonic-like (VSEL) stem cells from umbilical cord blood (UCB). Folia Histochem Cytobiol 2008; 46: 239-243.
24. Virant-Klun I, Zech N, Rozman P, Vogler A, Cvjeticanin B, Klemenc P et al. Putative stem cells with an embryonic character isolated from the ovarian surface epithelium of women with no naturally present follicles and oocytes. Differentiation 2008; 76: 843-856.
25. Nicholls H. VSELs: Is ideology overtaking science?. Cell Stem Cell 2013; 13: 143-144.
26. Abbott A. Doubt cast over tiny stem cells. Nature 2013; 499: 390.
27. Danova-Alt R, Heider A, Egger D, Cross M, Alt R. Very small embryonic-like stem cells purified from umbilical cord blood lack stem cell characteristics. PLoS One 2012; 7: E34899.
28. Szade K, Bukowska-Strakova K, Nowak WN, Szade A, Kachamakova-Trojanowska N, Zukowska M et al. Murine bone marrow Lin(-)Sca(-)1(þ)CD45(-) very small embryonic-like (VSEL) cells are heterogeneous population lacking Oct-4A expression. PLoS One 2013; 8: E63329.
29. Miyanishi M, Mori Y, Seita J, Chen J, Karten S, Chan C et al. Do pluripotent stem cells exist in adult mice as very small embryonic stem cells?. Stem Cell Rep 2013; 1: 198-208.
30. Ratajczak MZ, Majka M, Kucia M, Drukala J, Pietrzkowski Z, Peiper S et al. Expression of functional CXCR4 by muscle satellite cells and secretion of SDF-1 by muscle-derived fibroblasts is associated with the presence of both muscle progenitors in bone marrow and hematopoietic stem/progenitor cells in muscles. Stem Cells 2003; 21: 363-371.
31. Ratajczak MZ, Kucia M, Reca R, Majka M, Janowska-Wieczorek A, Ratajczak J. Stem cell plasticity revisited: CXCR4-positive cells expressing mRNA for early muscle, liver and neural cells 'hide out' in the bone marrow. Leukemia 2004; 18: 29-40.
32. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701-705.
33. LaBarge MA, Blau HM. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 2002; 111: 589-601.
34. Sanchez-Ramos Jr. Neural cells derived from adult bone marrow and umbilical cord blood. J Neurosci Res 2002; 69: 880-893.
35. Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M. A hypothesis for an embryonic origin of pluripotent Oct-4(þ) stem cells in adult bone marrow and other tissues. Leukemia 2007; 21: 860-867.
36. Beltrami AP, Cesselli D, Bergamin N, Marcon P, Rigo S, Puppato E et al. Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow). Blood 2007; 110: 3438-3446.
37. D'Ippolito G, Diabira S, Howard GA, Menei P, Roos BA, Schiller PC. Marrowisolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci 2004; 117: 2971-2981.
38. Kogler G, Sensken S, Airey JA, Trapp T, Muschen M, Feldhahn N et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 2004; 200: 123-135.
39. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41-49.
40. Ling TY, Kuo MD, Li CL, Yu AL, Huang YH, Wu TJ et al. Identification of pulmonary Oct-4þ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro. Proc Natl Acad Sci 2006; 103: 9530-9535.
41. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N et al. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284: 1168-1170.
42. Anjos-Afonso F, Bonnet D. Nonhematopoietic/endothelial SSEA-1þ cells define the most primitive progenitors in the adult murine bone marrow mesenchymal compartment. Blood 2007; 109: 1298-1306.
43. Yu H, Fang D, Kumar SM, Li L, Nguyen TK, Acs G et al. Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol 2006; 168: 1879-1888.
44. Li L, Clevers H. Coexistence of quiescent and active adult stem cells in mammals. Science 2010; 327: 542-545.
45. Ratajczak J, Wysoczynski M, Zuba-Surma E, Wan W, Kucia M, Yoder MC et al. Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells. Exp Hematol 2011; 39: 225-237.
46. Ratajczak J, Zuba-Surma E, Klich I, Liu R, Wysoczynski M, Greco N et al. Hematopoietic differentiation of umbilical cord blood-derived very small embryonic/epiblast-like stem cells. Leukemia 2011; 25: 1278-1285.
47. Wu JH, Wang HJ, Tan YZ, Li ZH. Characterization of rat very small embryonic-like stem cells and cardiac repair after cell transplantation for myocardial infarction. Stem Cells Dev 2012; 21: 1367-1379.
48. Virant-Klun I, Skutella T, Hren M, Gruden K, Cvjeticanin B, Vogler A et al. Isolation of small SSEA-4-positive putative stem cells from the ovarian surface epithelium of adult human ovaries by two different methods. Biomed Res Int 2013; 2013: 1-15.
49. Shin DM, Zuba-Surma EK, Wu W, Ratajczak J, Wysoczynski M, Ratajczak MZ et al. Novel epigenetic mechanisms that control pluripotency and quiescence of adult bone marrow-derived Oct4(þ) very small embryonic-like stem cells. Leukemia 2009; 23: 2042-2051.
50. Reik W, Walter J. Genomic imprinting: Parental influence on the genome. Nat Rev Genet 2001; 2: 21-32.
51. Hayashi K, Surani MA. Resetting the epigenome beyond pluripotency in the germline. Cell Stem Cell 2009; 4: 493-498.
52. Wylie C. Germ cells. Cell 1999; 96: 165-174.
53. Hayashi K, de Sousa Lopes SM, Surani MA. Germ cell specification in mice. Science 2007; 316: 394-396.
54. Ratajczak MZ, Shin DM, Schneider G, Ratajczak J, Kucia M. Parental imprinting regulates insulin-like growth factor signaling: A Rosetta Stone for understanding the biology of pluripotent stem cells, aging and cancerogenesis. Leukemia 2013; 27: 773-779.
55. Wojakowski W, Tendera M, Kucia M, Zuba-Surma E, Paczkowska E, Ciosek J et al. Mobilization of bone marrow-derived Oct-4þ SSEA-4þ very small embryoniclike stem cells in patients with acute myocardial infarction. J Am Coll Cardiol 2009; 53: 1-9.
56. Kucia MJ, Wysoczynski M, Wu W, Zuba-Surma EK, Ratajczak J, Ratajczak MZ. Evidence that very small embryonic-like stem cells are mobilized into peripheral blood. Stem Cells 2008; 26: 2083-2092.
57. Paczkowska E, Kucia M, Koziarska D, Halasa M, Safranow K, Masiuk M et al. Clinical evidence that very small embryonic-like stem cells are mobilized into peripheral blood in patients after stroke. Stroke 2009; 40: 1237-1244.
58. Kucia M, Dawn B, Hunt G, Guo Y, Wysoczynski M, Majka M et al. Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction. Circ Res 2004; 95: 1191-1199.
59. Drukala J, Paczkowska E, Kucia M, Mlynska E, Krajewski A, Machalinski B et al. Stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients after skin burn injury. Stem Cell Rev 2012; 8: 184-194.
60. Marlicz W, Zuba-Surma E, Kucia M, Blogowski W, Starzynska T, Ratajczak MZ. Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohn's disease. Inflamm Bowel Dis 2012; 18: 1711-1722.
61. Kucia M, Masternak M, Liu R, Shin DM, Ratajczak J, Mierzejewska K et al. The negative effect of prolonged somatotrophic/insulin signaling on an adult bone marrow-residing population of pluripotent very small embryonic-like stem cells (VSELs). Age (Dordr) 2013; 35: 315-330.
62. Ratajczak J, Shin DM, Wan W, Liu R, Masternak MM, Piotrowska K et al. Higher number of stem cells in the bone marrow of circulating low Igf-1 level Laron dwarf mice-novel view on Igf-1, stem cells and aging. Leukemia 2011; 25: 729-733.
63. Kucia M, Shin DM, Liu R, Ratajczak J, Bryndza E, Masternak MM et al. Reduced number of VSELs in the bone marrow of growth hormone transgenic mice indicates that chronically elevated Igf1 level accelerates age-dependent exhaustion of pluripotent stem cell pool: A novel view on aging. Leukemia 2011; 25: 1370-1374.
64. Ratajczak MZ, Shin DM, Kucia M. Very small embryonic/epiblast-like stem cells: A missing link to support the germ line hypothesis of cancer development?. Am J Pathol 2009; 174: 1985-1992.
65. Ratajczak MZ, Shin DM, Liu R, Marlicz W, Tarnowski M, Ratajczak J et al. Epiblast/ germ line hypothesis of cancer development revisited: Lesson from the presence of Oct-4þ cells in adult tissues. Stem Cell Rev 2010; 6: 307-316.
66. Shin DM, Liu R, Wu W, Waigel SJ, Zacharias W, Ratajczak MZ et al. Global gene expression analysis of very small embryonic-like stem cells reveals that the Ezh2-dependent bivalent domain mechanism contributes to their pluripotent state. Stem Cells Dev 2012; 21: 1639-1652.
67. Ratajczak MZ, Liu R, Ratajczak J, Kucia M, Shin DM. The role of pluripotent embryonic-like stem cells residing in adult tissues in regeneration and longevity. Differentiation 2011; 81: 153-161.
68. Shin DM, Liu R, Klich I, Wu W, Ratajczak J, Kucia M et al. Molecular signature of adult bone marrow-purified very small embryonic-like stem cells supports their developmental epiblast/germ line origin. Leukemia 2010; 24: 1450-1461.
69. Shin DM, Liu R, Klich I, Ratajczak J, Kucia M, Ratajczak MZ. Molecular characterization of isolated from murine adult tissues very small embryonic/ epiblast like stem cells (VSELs). Mol Cells 2010; 29: 533-538.
70. Rich IN. Primordial germ cells are capable of producing cells of the hematopoietic system in vitro. Blood 1995; 86: 463-472.
71. Ohtaka T, Matsui Y, Obinata M. Hematopoietic development of primordial germ cell-derived mouse embryonic germ cells in culture. Biochem Biophys Res Commun 1999; 260: 475-482.
72. Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS et al. Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol 2006; 8: 1114-1123.
73. Gao C, Kong NR, Li A, Tatetu H, Ueno S, Yang Y et al. SALL4 is a key transcription regulator in normal human hematopoiesis. Transfusion 2013; 53: 1037-1049.
74. Venkatraman A, He XC, Thorvaldsen JL, Sugimura R, Perry JM, Tao F et al. Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence. Nature 2013; 500: 345-349.
75. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-967.
76. Wakao S, Kitada M, Kuroda Y, Shigemoto T, Matsuse D, Akashi H et al. Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts. Proc Natl Acad Sci USA 2011; 108: 9875-9880.
77. Serafini M, Dylla SJ, Oki M, Heremans Y, Tolar J, Jiang Y et al. Hematopoietic reconstitution by multipotent adult progenitor cells: Precursors to long-Term hematopoietic stem cells. J Exp Med 2007; 204: 129-139.
78. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71-74.
79. Kuroda Y, Wakao S, Kitada M, Murakami T, Nojima M, Dezawa M. Isolation, culture and evaluation of multilineage-differentiating stress-enduring (Muse) cells. Nat Protoc 2013; 8: 1391-1415.
80. Jones RJ, Collector MI, Barber JP, Vala MS, Fackler MJ, May WS et al. Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood 1996; 88: 487-491.
81. Jones RJ, Wagner JE, Celano P, Zicha MS, Sharkis SJ. Separation of pluripotent haematopoietic stem cells from spleen colony-forming cells. Nature 1990; 347: 188-189.
82. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R et al. Multiorgan, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001; 105: 369-377.
83. Vacanti MP, Roy A, Cortiella J, Bonassar L, Vacanti CA. Identification and initial characterization of spore-like cells in adult mammals. J Cell Biochem 2001; 80: 455-460.
84. Bhartiya D, Shaikh A, Nagvenkar P, Kasiviswanathan S, Pethe P, Pawani H et al. Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy. Stem Cells Dev 2012; 21: 1-6.
85. McGuckin C, Jurga M, Ali H, Strbad M, Forraz N. Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro. Nat Protoc 2008; 3: 1046-1055.
86. McGuckin CP, Forraz N, Baradez MO, Navran S, Zhao J, Urban R et al. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif 2005; 38: 245-255.
87. Mikhail MA, M'Hamdi H, Welsh J, Levicar N, Marley SB, Nicholls JP et al. High frequency of fetal cells within a primitive stem cell population in maternal blood. Hum Reprod 2008; 23: 928-933.
88. Liu Y, Gao L, Zuba-Surma EK, Peng X, Kucia M, Ratajczak MZ et al. Identification of small Sca-1(þ), Lin(-), CD45(-) multipotential cells in the neonatal murine retina. Exp Hematol 2009; 37: 1096-11071107 e1.
89. Goldenberg-Cohen N, Avraham-Lubin BC, Sadikov T, Goldstein RS, Askenasy N. Primitive stem cells derived from bone marrow express glial and neuronal markers and support revascularization in injured retina exposed to ischemic and mechanical damage. Stem Cells Dev 2012; 21: 1488-1500.
90. Iskovich S, Goldenberg-Cohen N, Stein J, Yaniv I, Fabian I, Askenasy N. Elutriated stem cells derived from the adult bone marrow differentiate into insulinproducing cells in vivo and reverse chemical diabetes. Stem Cells Dev 2012; 21: 86-96.
91. Dawn B, Tiwari S, Kucia MJ, Zuba-Surma EK, Guo Y, Sanganalmath SK et al. Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction. Stem Cells 2008; 26: 1646-1655.
92. Zuba-Surma EK, Kucia M, Dawn B, Guo Y, Ratajczak MZ, Bolli R. Bone marrowderived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction. J Mol Cell Cardiol 2008; 44: 865-873.
93. Wojakowski W, Tendera M, Kucia M, Zuba-Surma E, Milewski K, Wallace-Bradley D et al. Cardiomyocyte differentiation of bone marrow-derived Oct-4þCXCR4þ SSEA-1þ very small embryonic-like stem cells. Int J Oncol 2010; 37: 237-247.
94. Zuba-Surma EK, Kucia M, Rui L, Shin DM, Wojakowski W, Ratajczak J et al. Fetal liver very small embryonic/epiblast like stem cells follow developmental migratory pathway of hematopoietic stem cells. Ann N Y Acad Sci 2009; 1176: 205-218.
95. Zuba-Surma EK, Kucia M, Wu W, Klich I, Lillard JW, Ratajczak J et al. Very small embryonic-like stem cells are present in adult murine organs: ImageStreambased morphological analysis and distribution studies. Cytometry A 2008; 73A: 1116-1127.
96. Zuba-Surma EK, Kucia M, Abdel-Latif A, Dawn B, Hall B, Singh R et al. Morphological characterization of very small embryonic-like stem cells (VSELs) by ImageStream system analysis. J Cell Mol Med 2008; 12: 292-303.
97. Zuba-Surma EK, Klich I, Greco N, Laughlin MJ, Ratajczak J, Ratajczak MZ. Optimization of isolation and further characterization of umbilical-cord- bloodderived very small embryonic/ epiblast-like stem cells (VSELs). Eur J Haematol 2010; 84: 34-46.
98. Invitrogen. Sytos Green-Fluorescent Nucleic Acid Stains. web http:// probes.invitrogen.com/media/pis/mp07572.pdf
99. Wlodkowic D, Skommer J, Darzynkiewicz Z. Rapid quantification of cell viability and apoptosis in B-cell lymphoma cultures using cyanine SYTO probes. Methods Mol Biol 2011; 740: 81-89.
100. Zuba-Surma EK, Ratajczak MZ. Overview of very small embryonic-like stem cells (VSELs) and methodology of their identification and isolation by flow cytometric methods. Curr Protoc Cytom 2010, Chapter 9, pp 9.29.1-9.29.15.
101. Liu R, Klich I, Ratajczak J, Ratajczak MZ, Zuba-Surma EK. Erythrocytederived microvesicles may transfer phosphatidylserine to the surface of nucleated cells and falsely 'mark' them as apoptotic. Eur J Haematol 2009; 83: 220-229.
102. Shapiro HM. Practical Flow Cytometry. 3rd edn (John Wiley & Sons, Inc., 2003.
103. Huang Y, Kucia M, Hussain LR, Wen Y, Xu H, Yan J et al. Bone marrow transplantation temporarily improves pancreatic function in streptozotocin- induced diabetes: Potential involvement of very small embryonic-like cells. Transplantation 2010; 89: 677-685.
104. Zuba-Surma EK, Ratajczak MZ. Analytical capabilities of the ImageStream cytometer. Methods Cell Biol 2011; 102: 207-230.
105. Amnis. FlowSight - brochure. Amnis Corp 2011, web https://amnis.com/ documents/ brochures/FSBrochure Final.pdf
106. Kassmer SH, Bruscia EM, Zhang PX, Krause DS. Nonhematopoietic cells are the primary source of bone marrow-derived lung epithelial cells. Stem Cells 2012; 30: 491-499.
107. Bhartiya D, Unni S, Parte S, Anand S. Very small embryonic-like stem cells: Implications in reproductive biology. Biomed Res Int 2013; 2013: 682326..