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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Genes &amp; Cells</journal-id><journal-title-group><journal-title xml:lang="en">Genes &amp; Cells</journal-title><trans-title-group xml:lang="ru"><trans-title>Гены и Клетки</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>Genes and Cells</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-1829</issn><issn publication-format="electronic">2500-2562</issn><publisher><publisher-name xml:lang="en">Human Stem Cells Institute</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">121568</article-id><article-id pub-id-type="doi">10.23868/gc121568</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Статьи</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Characterization and ex vivo expansion umbilical cord bloodhematopoietic stem and progenitor cells</article-title><trans-title-group xml:lang="ru"><trans-title>Характеристика и ex vivo экспансия гемопоэтических стволовых и прогениторных клеток пуповинной крови</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Ufimtceva</surname><given-names>A. I</given-names></name><name xml:lang="ru"><surname>Уфимцева</surname><given-names>А. И</given-names></name></name-alternatives><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kanov</surname><given-names>E. V</given-names></name><name xml:lang="ru"><surname>Канов</surname><given-names>Е. В</given-names></name></name-alternatives><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">«Trans-Technologies Ltd», Saint-Petersburg</institution></aff><aff><institution xml:lang="ru">ООО «Транс-Технологии», Санкт-Петербург</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2012-12-15" publication-format="electronic"><day>15</day><month>12</month><year>2012</year></pub-date><volume>7</volume><issue>4</issue><issue-title xml:lang="en">VOL 7, NO4 (2012)</issue-title><issue-title xml:lang="ru">ТОМ 7, №4 (2012)</issue-title><fpage>21</fpage><lpage>27</lpage><history><date date-type="received" iso-8601-date="2023-01-11"><day>11</day><month>01</month><year>2023</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2012, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2012, Эко-Вектор</copyright-statement><copyright-year>2012</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://genescells.ru/2313-1829/article/view/121568">https://genescells.ru/2313-1829/article/view/121568</self-uri><abstract xml:lang="en"><p>Umbilical cord blood as an alternative source of hematopoietic stem and progenitor cells is widely used in clinical practice. Thereby it is necessary to characterize hematopoietic progenitors and to define among them the most «primitive» cells with the greatest repopulating potential. In addition absolute number of hematopoietic stem and progenitor cells is limited, so it is important to find ways of increasing their ex vivo. Currently several methods of in vitro and in vivo characterize hematopoietic progenitors and of ex vivo expansion of these cells have been developed. In this review we describe this methods, as well as problems with their translation to the clinical transplantation.</p></abstract><trans-abstract xml:lang="ru"><p>Пуповинная кровь, как один из альтернативных источников гемопоэтических стволовых и прогениторных клеток, в настоящее время активно применяется в клинической практике. В связи с этим необходимо четко охарактеризовать содержащуюся в ней популяцию гемопоэтических предшественников и обнаружить среди них клетки с наибольшей способностью к восстановлению кроветворения. Кроме того, абсолютное количество гемопоэтических стволовых и кроветворных клеток в пуповинной крови невелико, что заставляет искать способы их наращивания ex vivo. В настоящее время разработан ряд методов определения характеристик прогениторных клеток пуповинной крови in vitro и in vivo и их экспансии ex vivo. В данном обзоре рассмотрены эти методы, а также проблемы их адаптации для практики клинической трансплантологии.</p></trans-abstract><kwd-group xml:lang="en"><kwd>hematopoietic stem and progenitor cells</kwd><kwd>umbilical cord blood</kwd><kwd>methods of characterization</kwd><kwd>ex vivo expansion</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>гемопоэтические стволовые и прогениторные клетки</kwd><kwd>пуповинная кровь</kwd><kwd>методы характеризации</kwd><kwd>ex vivo экспансия</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Thomas E.D., Lochte H.L., Lu W.C. et al. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N. Engl. J. Med. 1957; 257(11): 491-6.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Till J.E., McCulloch E.A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res. 1961; 14: 213-22.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Forsberg E.C., Prohaska S.S., Katzman S. et al. Differential expression of novel potential regulators in hematopoietic stem cells. PLoS Genet. 2005; 1(3): e28.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Schoemans H., Verfaillie C. Cellular biology of hematopoiesis. In: Hoffman R., Benz E.J., Shattil S.J. et al., editors. Hematology: Basic Principles and Practice. 5th edn. Part III. Philadelphia: Elsevier Churchill Livingston; 2008: 358-71.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Alenzi F.Q., Alenazi B.Q., Ahmad S.Y. et al. The haemopoietic stem cell: between apoptosis and self renewal. Yale J. Biol. Med. 2009; 82(1): 7-18.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Zhu J., Emerson S.G. Hematopoietic cytokines, transcription factors and lineage commitment. Oncogene 2002; 21(21): 3295-313.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Dahl R., Hromas R. Transcription factors in normal and malignant hematopoiesis. In: Hoffman R., Benz E.J. Jr., Shattil S.J. et al., editors. Hematology: Basic Principles and Practice. 5th edn. Part III. Philadelphia: Elsevier Churchill Livingston; 2008: 372-95.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Lessard J., Faubert A., Sauvageau G. Genetic programs regulating HSC specification, maintenance and expansion. Oncogene 2004; 23(43): 7199-209.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Haylock D.N., Nilsson S.K. Stem cell regulation by the hematopoietic stem cell niche. Cell Cycle 2005; 4: 1353-5. ского применения. Однако необходимо решить целый ряд технических задач для культивирования клеток в объемах, которые требуются для трансплантации. Кроме того, важен строгий контроль применяемых методик для обеспечения безопасности пациентов.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Zhang C.C., Lodish H.F. Cytokines regulating hematopoietic stem cell function. Curr. Opin. Hematol. 2008; 15(4): 307-11.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Oh I.H., Kwon K.R. Concise review: multiple niches for hematopoietic stem cell regulations. Stem Cells 2010; 28(7): 1243-9.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Arai F., Hirao A., Ohmura M. et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 2004; 118(2): 149-61.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Cerdan C., Bhatia M. Novel roles for Notch, Wnt and Hedgehog in hematopoesis derived from human pluripotent stem cells. Int. J. Dev. Biol. 2010; 54(6-7): 955-63.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Delaney C., Ratajczak M.Z., Laughlin M.J. Strategies to enhance umbilical cord blood stem cell engraftment in adult patients. Expert. Rev. Hematol. 2010; 3(3): 273-83.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Hofmeister C.C., Zhang J., Knight K.L. et al. Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche. Bone Marrow Transplant. 2007; 39(1): 11-23.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Peled A., Petit I., Kollet O. et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 1999; 283(5403): 845-8.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Aiuti A., Webb I.J., Bleul C. et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J. Exp. Med. 1997; 185(1): 111-20.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Peled A., Kollet O., Ponomaryov T. et al. The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34( + ) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood 2000; 95(11): 3289-96.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Avigdor A., Goichberg P., Shivtiel S. et al. CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/ progenitor cells to bone marrow. Blood 2004; 103(8): 2981—9.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Christopherson K.W., Hangoc G., Broxmeyer H.E. Cell surface peptidase CD26/dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1 alpha-mediated chemotaxis of human cord blood CD34+ progenitor cells. J. Immunol. 2002; 169(12): 7000—8.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Krause D.S., Fackler M.J., Civin C.I. et al. CD34: structure, biology, and clinical utility. Blood 1996; 87(1): 1—13.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Sutherland D.R., Anderson L., Keeney M. et al. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J. Hematother. 1996; 5(3): 213—26.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Craig W., Kay R., Cutler R.L. et al. Expression of Thy-1 on human hematopoietic progenitor cells. J. Exp. Med. 1993; 177(5): 1331—42.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Yin A.H., Miraglia S., Zanjani E.D. et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997; 90(12): 5002—12.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Encabo A., Mateu E., Carbonell-Uberos F. et al. CD34 + CD38- is a good predictive marker of cloning ability and expansion potential of CD34+ cord blood cells. Transfusion 2003; 43(3): 383—9.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Zanjani E.D., Almeida-Porada G., Livingston A.G. et al. Human bone marrow CD34— cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells. Exp. Hematol. 1998; 26(4): 353—60.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Bhatia M., Bonnet D., Murdoch B. et al. A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat. Med. 1998; 4(9): 1038—45.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Goodell M.A., Rosenzweig M., Kim H. et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat. Med. 1997; 3(12): 1337—45.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Wang J., Kimura T., Asada R. et al. SCID-repopulating cell activity of human cord blood-derived CD34- cells assured by intra-bone marrow injection. Blood 2003; 101(8): 2924—31.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Sonoda Y. Immunophenotype and functional characteristics of human primitive CD34-negative hematopoietic stem cells: the significance of the intra-bone marrow injection. J. Autoimmun. 2008; 30(3): 136—44.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Yahata T., Ando K., Sato T. et al. A highly sensitive strategy for SCID-repopulating cell assay by direct injection of primitive human hematopoietic cells into NOD/SCID mice bone marrow. Blood 2003; 101(8): 2905—13.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Kimura T., Asada R., Wang J. et al. Identification of long-term repopulating potential of human cord blood-derived CD34-flt3- severe combined immunodeficiency-repopulating cells by intra-bone marrow injection. Stem Cells 2007; 25(6): 1348—55.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Chen C.Z., Li M., de Graaf D. et al. Identification of endoglin as a functional marker that defines long-term repopulating hematopoietic stem cells. PNAS USA 2002; 99(24): 15468—73.</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Balazs A.B., Fabian A.J., Esmon C.T. et al. Endothelial protein C receptor (CD201) explicitly identifies hematopoietic stem cells in murine bone marrow. Blood 2006; 107(6): 2317—21.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Wagers A.J. Stem cell grand SLAM. Cell 2005; 121(7): 967—70.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Challen G.A., Little M.H. A side order of stem cells: the SP phenotype. Stem Cells 2006; 24: 3.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Goodell M.A., Brose K., Paradis G. et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 1996; 183(4): 1797—806.</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Liu H., Verfaillie C.M. Myeloid-lymphoid initiating cells (ML-IC) are highly enriched in the rhodamine-c-kit( + )CD33(-)CD38(-) fraction of umbilical cord CD34( + ) cells. Exp. Hematol. 2002; 30: 582.</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>McKenzie J.L., Takenaka K., Gan O.I. et al. Low rhodamine 123 retention identifies long-term human hematopoietic stem cells within the Lin-CD34+CD38- population. Blood 2007; 109: 543.</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Arai F., Hirao A., Suda T. Regulation of hematopoietic stem cells by the niche. Trends Cardiovasc. Med. 2005; 15(2): 75—9.</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Pierre-Louis O., Clay D., Brunet de la Grange P. et al. Dual SP/ALDH functionalities refine the human hematopoietic Lin- CD34+CD38— stem/progenitor cell compartment. Stem Cells 2009; 27(10): 2552—62.</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Hess D.A., Meyerrose T.E., Wirthlin L. et al. Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood 2004; 104(6): 1648—55.</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Christ O., Lucke K., Imren S. et al. Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity. Haematologica 2007; 92(9): 1165—72.</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Lioznov M.V., Freiberger P., Kroger N. et al. Aldehyde dehydrogenase activity as a marker for the quality of hematopoietic stem cell transplants. Bone Marrow Transplant. 2005; 35(9): 909—14.</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Fallon P., Gentry T., Balber A.E. et al. Mobilized peripheral blood SSCloALDHbr cells have the phenotypic and functional properties of primitive haematopoietic cells and their number correlates with engraftment following autologous transplantation. Br. J. Haematol. 2003; 122: 99—108.</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Yang H., Acker J.P., Cabuhat M. et al. Association of postthaw viable CD34+ cells and CFU-GM with time to hematopoietic engraftment. Bone Marrow Transplant. 2005; 35(9): 881—7.</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>International standards for cord blood collection, processing, testing, banking, selection, and release. 3rd Edn; 2006.</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Nadali G., de Wynter E.A., Perandin F. et al. Regulation of the proliferative potential of cord blood long-term culture-initiating cells (LTC-IC) by different stromal cell lines: implications for LTC-IC measurement. Haematologica 1998; 83(12): 1059—65.</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Denning-Kendall P., Singha S., Bradley B. et al. Cobblestone area-forming cells in human cord blood are heterogeneous and differ from long-term culture-initiating cells. Stem Cells 2003; 21(6): 694—701.</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Bhatia M., Wang J.C., Kapp U. et al. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. PNAS USA 1997; 94(10): 5320—5.</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Chao N.J., Emerson S.G., Weinberg K.I. Stem cell transplantation (cord blood transplants). Hematology Am. Soc. Hematol. Educ. Program. 2004; 354—71.</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Gammaitoni L., Weisel K.C., Gunetti M. et al. Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication. Blood 2004; 103(12): 4440—8.</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Harris D.T., Schumacher M.J., Locascio J. et al. Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. PNAS USA 1992; 89(21): 10006—10.</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Rocha V., Gluckman E. Eurocord-Netcord registry and European Blood and Marrow Transplant group. Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft- and transplantation-related factors. Br. J. Haematol. 2009; 147(2): 262—74.</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Koestenbauer S., Zisch A., Dohr G. et al. Protocols for hematopoietic stem cell expansion from umbilical cord blood. Cell Transplant. 2009; 18(10): 1059—68.</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Gluckman E., Rocha V. Cord blood transplantation: state of the art. Haematologica 2009; 94(4): 451—4.</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Laughlin M.J., Eapen M., Rubinstein P. et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N. Engl. J. Med. 2004; 351(22): 2265—75.</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Gilner J.B., Walton W.G., Gush K. et al. Antibodies to stem cell marker antigens reduce engraftment of hematopoietic stem cells. Stem Cells 2007; 25(2): 279—88.</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Kobayashi M., Laver J.H., Lyman S.D. et al. Thrombopoietin, steel factor and the ligand for flt3/flk2 interact to stimulate the proliferation of human hematopoietic progenitors in culture. Int. J. Hematol. 1997; 66(4): 423—34.</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Herrera C., Sanchez J., Torres A. et al. Early-acting cytokine- driven ex vivo expansion of mobilized peripheral blood CD34+ cells generates post-mitotic offspring with preserved engraftment ability in non-obese diabetic/severe combined immunodeficient mice. Br. J. Haematol. 2001; 114(4): 920—30.</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Zandstra P.W., Conneally E., Petzer A.L. et al. Cytokine manipulation of primitive human hematopoietic cell self-renewal. PNAS USA 1997; 94(9): 4698—703.</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Berger M., Fagioli F., Piacibello W. et al. Role of different medium and growth factors on placental blood stem cell expansion: an in vitro and in vivo study. Bone Marrow Transplant. 2002; 29(5): 443—8.</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Henschler R., Brugger W., Luft T. et al. Maintenance of transplantation potential in ex vivo expanded CD34( + )-selected human peripheral blood progenitor cells. Blood 1994; 84(9): 2898—903.</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Kobari L., Pflumio F., Giarratana M. et al. In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34+ cord blood cells. Exp. Hematol. 2000; 28(12): 1470—80.</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Donaldson C., Denning-Kendall P., Bradley B. et al. The CD34( + ) CD38(neg) population is significantly increased in haemopoietic cell expansion cultures in serum-free compared to serum-replete conditions: dissociation of phenotype and function. Bone Marrow Transplant. 2001; 27(4): 365—71.</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Shpall E.J., Quinones R., Giller R. et al. Transplantation of ex vivo expanded cord blood. Biol. Blood Marrow Transplant. 2002; 8(7): 368—76.</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Mohamed A.A., Ibrahim A.M., El-Masry M.W. et al. Ex vivo expansion of stem cells: defining optimum conditions using various cytokines. Lab. Hematol. 2006; 12(2): 86—93</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Robinson S.N., Ng J., Niu T. et al. Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cell. Bone Marrow Transplant. 2006; 37(4): 359—66.</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Wagner W., Roderburg C., Wein F. et al. Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors. Stem Cells 2007; 25(10): 2638—47.</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Kadereit S., Deeds L.S., Haynesworth S.E. et al. Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34+/CD38— early progenitors cultured over human mscs as a feeder layer. Stem Cells 2002; 20(6): 573—82.</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Mishima S., Nagai A., Abdullah S. et al. Effective ex vivo expansion of hematopoietic stem cells using osteoblast-differentiated mesenchymal stem cells is CXCL12 dependent. Eur. J. Haematol. 2010; 84(6): 538-46.</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Jang Y.K., Jung D.H., Jung M.H. et al. Mesenchymal stem cells feeder layer from human umbilical cord blood for ex vivo expanded growth and proliferation of hematopoietic progenitor cells. Ann. Hematol. 2006; 85(4): 212-25.</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Yildirim S., Boehmler A.M., Kanz L. et al. Expansion of cord blood CD34+ hematopoietic progenitor cells in coculture with autologous umbilical vein endothelial cells (HUVEC) is superior to cytokine-supplemented liquid culture. Bone Marrow Transplant. 2005; 36(1): 71-9.</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Ehring B., Biber T.M., Upton T.M. et al. Expansion of HPCs from cord blood in a novel 3D matrix. Cytotherapy 2003; 5: 490-9.</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Feng Q., Chai C., Jiang X.S. et al. Expansion of engrafting human hematopoietic stem/progenitor cells in three-dimensional scaffolds with surfaceimmobilized fibronectin. J. Biomed. Mater. Res. 2006; 78: 781-91.</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Takagi M., Iemoto N., Yoshida T. Effect of concentrations of murine stromal and hematopoietic cells on the progenitors expansion in their three-dimensional coculture in nonwoven fabrics. J. Biosci. Bioeng. 2002; 94(4): 365-7.</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>Okamoto T., Takagi M., Soma T. et al. Effect of heparin addition on expansion of cord blood hematopoietic progenitor cells in threedimensional coculture with stromal cells in nonwoven fabrics. J. Artif. Organs. 2004; 7(4): 194-202.</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>Purton L.E., Bernstein I.D., Collins S.J. All-trans retinoic acid delays the differentiation of primitive hematopoietic precursors (lin-c-kit + Sca-1( + )) while enhancing the terminal maturation of committed granulocyte/monocyte progenitors. Blood 1999; 94(2): 483-95.</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>Peled T., Landau E., Prus E. et al. Cellular copper content modulates differentiation and self-renewal in cultures of cord blood- derived CD34+ cells. Br. J. Haematol. 2002; 116(3): 655-61.</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>Boitano A.E., Wang J., Romeo R. et al. Cooke M.P. aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 2010; 329(5997): 1345-8.</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>Delaney C., Heimfeld S., Brashem-Stein C. et al. Notch- mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat. Med. 2010; 16(2): 232-6.</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>Drake A.C., Khoury M., Leskov I. et al. Human CD34+ CD133+ hematopoietic stem cells cultured with growth factors including angptl5 efficiently engraft adult NOD-SCID Il2rc2/2 (NSG) mice. PLoS One 2011; 6(4): e18382.</mixed-citation></ref><ref id="B83"><label>83.</label><mixed-citation>Trevis A., Peled T., Rosen O., inventors; Gamida-Cell Ltd., assignee. Ex-vivo expansion of hematopoietic stem cell populations in mononuclear cell cultures. AU patent 2005200679. 2005 Feb16.</mixed-citation></ref><ref id="B84"><label>84.</label><mixed-citation>De Felice L., Tatarelli C., Mascolo M.G. et al. Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells. Cancer Res. 2005; 65(4): 1505-13.</mixed-citation></ref><ref id="B85"><label>85.</label><mixed-citation>Milhem M., Mahmud N., Lavelle D. et al. Modification of hematopoietic stem cell fate by 5aza 2'deoxycytidine and trichostatin A. Blood 2004; 103(11): 4102-10.</mixed-citation></ref><ref id="B86"><label>86.</label><mixed-citation>Yang M., Li K., Ng P.C. et al. Promoting effects of serotonin on hematopoiesis: ex vivo expansion of cord blood CD34+ stem/progenitor cells, proliferation of bone marrow stromal cells, and antiapoptosis. Stem Cells 2007; 25(7): 1800-6.</mixed-citation></ref><ref id="B87"><label>87.</label><mixed-citation>Himburg H.A., Muramoto G.G., Daher P. et al. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat. Med. 2010; 16(4): 475-82.</mixed-citation></ref><ref id="B88"><label>88.</label><mixed-citation>Pirih F.Q., Michalski M.N., Cho S.W. et al. Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6. PLoS One 2010; 5(10): e13657.</mixed-citation></ref><ref id="B89"><label>89.</label><mixed-citation>Kowalczyk M., Waldron K., Kresnowati P. Process challenges relating to hematopoietic stem cell cultivation in bioreactors. J. Ind. Microbiol. Biotechnol. 2011; 38(7): 761-7.</mixed-citation></ref><ref id="B90"><label>90.</label><mixed-citation>Nielsen L.K. Bioreactors for hematopoietic cell culture. Annu. Rev. Biomed. Eng. 1999; 1: 129-52</mixed-citation></ref><ref id="B91"><label>91.</label><mixed-citation>de Lima M., McMannis J., Gee A. et al. Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial. Bone Marrow Transplant. 2008; 41(9): 771-8.</mixed-citation></ref></ref-list></back></article>
