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Ex Vivo Expanded Hematopoietic Stem Cells for Ischemia

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Stem Cells and Cancer Stem Cells, Volume 2

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 2))

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Abstract

Ischemia related diseases are on rise worldwide and have been shown to cause irreversible damage to the cells due to the blockage of blood supply to the tissue. Conventional therapies are less effective as they do not consider repair of the damaged tissues. Thus, alternative, stem cell-based therapies are currently under investigation. For example, hematopoietic stem cells (HSCs) were shown to give rise to vascular cells involved in neoangiogenesis; so, they have been tested in variety of animal models and small-scale clinical trials. Improvement in blood flow and tissue functionality was observed and adverse effects were not apparent. However, success of stem cell therapy is limited by the number of functional stem cells for clinical application. Numerous attempts are underway to address this issue via strategies that involve ex vivo expansion of stem cells preserving their stemness. This chapter outlines the mechanism of therapeutic angiogenesis, sources of HSCs, various methods of ex vivo expansion of HSCs via genetic regulators, cytokines and biomaterial scaffolds, and their preclinical and clinical applications.

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References

  • Aggarwal R, Pompili VJ, Das H (2010) Genetic modification of ex-vivo expanded stem cells for clinical application. Front Biosci 15:854–871

    Article  PubMed  CAS  Google Scholar 

  • Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, Ito K, Koh GY, Suda T (2004) Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118:149–161

    Article  PubMed  CAS  Google Scholar 

  • Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    Article  PubMed  CAS  Google Scholar 

  • Bagley J, Rosenzweig M, Marks DF, Pykett MJ (1999) Extended culture of multipotent hematopoietic progenitors without cytokine augmentation in a novel three-dimensional device. Exp Hematol 27:496–504

    Article  PubMed  CAS  Google Scholar 

  • Blank U, Karlsson G, Karlsson S (2008) Signaling pathways governing stem-cell fate. Blood 111:492–503

    Article  PubMed  CAS  Google Scholar 

  • Bryder D, Jacobsen SE (2000) Interleukin-3 supports expansion of long-term multilineage repopulating activity after multiple stem cell divisions in vitro. Blood 96:1748–1755

    PubMed  CAS  Google Scholar 

  • Chua KN, Chai C, Lee PC, Tang YN, Ramakrishna S, Leong KW, Mao HQ (2006) Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells. Biomaterials 27:6043–6051

    Article  PubMed  CAS  Google Scholar 

  • Chua KN, Chai C, Lee PC, Ramakrishna S, Leong KW, Mao HQ (2007) Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells. Exp Hematol 35:771–781

    Article  PubMed  CAS  Google Scholar 

  • Das H, Abdulhameed N, Joseph M, Sakthivel R, Mao HQ, Pompili VJ (2009a) Ex vivo nanofiber expansion and genetic modification of human cord blood-derived progenitor/stem cells enhances vasculogenesis. Cell Transplant 18:305–318

    Article  PubMed  Google Scholar 

  • Das H, George JC, Joseph M, Das M, Abdulhameed N, Blitz A, Khan M, Sakthivel R, Mao HQ, Hoit BD, Kuppusamy P, Pompili VJ (2009b) Stem cell therapy with overexpressed VEGF and PDGF genes improves cardiac function in a rat infarct model. PLoS One 4:e7325

    Article  PubMed  Google Scholar 

  • Ding S, Wu TY, Brinker A, Peters EC, Hur W, Gray NS, Schultz PG (2003) Synthetic small molecules that control stem cell fate. Proc Natl Acad Sci USA 100:7632–7637

    Article  PubMed  CAS  Google Scholar 

  • Folkman J, Bach M, Rowe JW, Davidoff F, Lambert P, Hirsch C, Goldberg A, Hiatt HH, Glass J, Henshaw E (1971) Tumor angiogenesis – therapeutic implications. New Eng J Med 285:1182

    Article  PubMed  CAS  Google Scholar 

  • Franke K, Pompe T, Bornhauser M, Werner C (2007) Engineered matrix coatings to modulate the adhesion of CD133+ human hematopoietic progenitor cells. Biomaterials 28:836–843

    Article  PubMed  CAS  Google Scholar 

  • Gupta R, Tongers J, Losordo DW (2009) Human studies of angiogenic gene therapy. Circ Res 105:724–736

    Article  PubMed  CAS  Google Scholar 

  • Himburg HA, Muramoto GG, Daher P, Meadows SK, Russell JL, Doan P, Chi JT, Salter AB, Lento WE, Reya T, Chao NJ, Chute JP (2010) Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat Med 16:475–482

    Article  PubMed  CAS  Google Scholar 

  • Iruela-Arispe ML, Davis GE (2009) Cellular and molecular mechanisms of vascular lumen formation. Dev Cell 16:222–231

    Article  PubMed  CAS  Google Scholar 

  • LaIuppa JA, McAdams TA, Papoutsakis ET, Miller WM (1996) Culture materials affect ex vivo expansion of hematopoietic progenitor cells. J Biomed Mater Res 36:347–359

    Article  Google Scholar 

  • Li Y, Ma T, Kniss DA, Yang ST, Lasky LC (2001) Human cord cell hematopoiesis in three-dimensional nonwoven fibrous matrices: in vitro simulation of the marrow microenvironment. J Hematother Stem Cell Res 10:355–368

    Article  PubMed  CAS  Google Scholar 

  • Lin Y, Weisdorf DJ, Solovey A, Hebbel RP (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105:71–77

    Article  PubMed  CAS  Google Scholar 

  • Losordo DW, Dimmeler S (2004) Therapeutic angiogenesis and vasculogenesis for ischemic disease: part II: cell-based therapies. Circulation 109:2692–2697

    Article  PubMed  Google Scholar 

  • Mohr JC, de Pablo JJ, Palecek SP (2006) 3-D microwell culture of human embryonic stem cells. Biomaterials 27:6032–6042

    Article  PubMed  CAS  Google Scholar 

  • Mommaas B, Stegehuis-Kamp JA, van Halteren AG, Kester M, Enczmann J, Wernet P, Kogler G, Mutis T, Brand A, Goulmy E (2005) Cord blood comprises antigen-experienced T cells specific for maternal minor histocompatibility antigen HA-1. Blood 105:1823–1827

    Article  PubMed  CAS  Google Scholar 

  • Nygren JM, Jovinge S, Breitbach M, Sawen P, Roll W, Hescheler J, Taneera J, Fleischmann BK, Jacobsen SE (2004) Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 10:494–501

    Article  PubMed  CAS  Google Scholar 

  • Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S (2000) Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95:952–958

    PubMed  CAS  Google Scholar 

  • Rafii S, Lyden D (2003) Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 9:702–712

    Article  PubMed  CAS  Google Scholar 

  • Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM (2004) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 44:1690–1699

    Article  PubMed  Google Scholar 

  • Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, Branco RV, Oliveira EM, He R, Geng YJ, Willerson JT, Perin EC (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156

    Article  PubMed  CAS  Google Scholar 

  • Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361:45–46

    Article  PubMed  Google Scholar 

  • Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP (2003) Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361:47–49

    Article  PubMed  Google Scholar 

  • Wagers AJ, Sherwood RI, Christensen JL, Weissman IL (2002) Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297:2256–2259

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by National Institutes of Health grants, K01 AR054114 (NIAMS), SBIR R44 HL092706-01 (NHLBI), R21 CA143787 (NCI) and The Ohio State University start-up fund. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Cardiovascular Stem Cell Research Laboratories, Davis Heart and Lung Research Institute, Columbus, OH, 43210, USA

    Jingwei Lu, Reeva Aggarwal, Vincent J. Pompili & Hiranmoy Das

Authors
  1. Jingwei Lu
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  2. Reeva Aggarwal
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  3. Vincent J. Pompili
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  4. Hiranmoy Das
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Correspondence to Hiranmoy Das .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Lu, J., Aggarwal, R., Pompili, V.J., Das, H. (2012). Ex Vivo Expanded Hematopoietic Stem Cells for Ischemia. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 2. Stem Cells and Cancer Stem Cells, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2016-9_23

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