Review article
Homing and engraftment of progenitor cells: A prerequisite for cell therapy

https://doi.org/10.1016/j.yjmcc.2008.01.004Get rights and content

Abstract

Cell therapy is a promising therapeutic option for treating patients with ischemic diseases. The efficiency of cell therapy to augment recovery after ischemia depends on the sufficient recruitment of applied cells to the target tissue. Using in vivo imaging techniques the extent of homing was shown to be rather low in most experimental and clinical studies. The elucidation of the molecular mechanisms of homing of different progenitor cell subpopulation to sites of injury is essential for the development of new specific therapeutic strategies, in order to improve the efficacy of cell-based therapies. Homing to sites of active neovascularization is a complex process depending on a timely and spatially orchestrated interplay between chemokines (e.g. SDF-1), chemokine receptors, intracellular signaling, adhesion molecules (selectins and integrins) and proteases. The review will focus on the mechanisms underlying homing of adult bone marrow-derived hematopoietic cells, mesenchymal stem cells, and vasculogenic circulating cells and discuss strategies how to optimize cell engraftment.

Section snippets

Extent of cell homing in experimental and clinical studies

In order to determine progenitor cell trafficking and in vivo distribution, life imaging is essential. Several non-invasive imaging modalities can be used to assess the biodistribution of the applied cells over time to track homing of the cells to the target tissue but also to visualize the up-take to other organs and tissues where cells potentially may exhibit unwanted side-effects. Non-invasive imaging has been performed by direct labeling of cells with radionucleotides for single-photon

Mechanism of homing

Homing and engraftment is a prerequisite for all cell types to exhibit any type of activity in the target tissue particularly when cells are infused via the vascular route. While the homing of leukocytes to sites of inflammation is well studied [16], [17], [18], the mechanisms of progenitor cell homing to sites of ischemia or injury are poorly understood. During inflammation, the recruitment of inflammatory cells requires a coordinated sequence of multistep adhesive and signaling events

Strategies to augment homing and engraftment

In principle two strategies might be used to augment homing of cells: pre-treat the cells to activate incorporation or to pre-treat the target tissue in order to provide the cytokines and chemoattractant factors to stimulate progenitor cell incorporation. The currently experimentally used strategies are based on the basic discoveries outlined in detail above and are summarized in Fig. 4.

References (76)

  • B. Heissig et al.

    Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand

    Cell

    (2002)
  • M. Tamura et al.

    In vivo trafficking of endothelial progenitor cells their possible involvement in the tumor neovascularization

    Life Sci

    (2004)
  • G.A. McQuibban et al.

    Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1

    J Biol Chem

    (2001)
  • R.F. Wynn et al.

    A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow

    Blood

    (2004)
  • S. Dimmeler et al.

    Unchain my heart: the scientific foundations of cardiac repair

    J Clin Invest

    (2005)
  • A. Abdel-Latif et al.

    Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis

    Arch Intern Med

    (2007)
  • V. Schachinger et al.

    Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial

    Eur Heart J

    (2006)
  • F.M. Bengel et al.

    Cell-based therapies and imaging in cardiology

    Eur J Nucl Med Mol Imaging

    (2005)
  • A. Aicher et al.

    Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling

    Circulation

    (2003)
  • D. Hou et al.

    Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials

    Circulation

    (2005)
  • W. Brenner et al.

    111In-labeled CD34+ hematopoietic progenitor cells in a rat myocardial infarction model

    J Nucl Med

    (2004)
  • M. Kurpisz et al.

    Bone marrow stem cell imaging after intracoronary administration

    Int J Cardiol

    (2006)
  • V. Caveliers et al.

    In vivo visualization of 111In labeled CD133+ peripheral blood stem cells after intracoronary administration in patients with chronic ischemic heart disease

    Q J Nucl Med Mol Imaging

    (2007)
  • E. Goussetis et al.

    Intracoronary infusion of CD133+ and CD133−CD34+ selected autologous bone marrow progenitor cells in patients with chronic ischemic cardiomyopathy: cell isolation, adherence to the infarcted area, and body distribution

    Stem Cells

    (2006)
  • M. Hofmann et al.

    Monitoring of bone marrow cell homing into the infarcted human myocardium

    Circulation

    (2005)
  • J.M. Hill et al.

    Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells

    Circulation

    (2003)
  • D.L. Kraitchman et al.

    In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction

    Circulation

    (2003)
  • D.L. Kraitchman et al.

    Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction

    Circulation

    (2005)
  • B.A. Imhof et al.

    Adhesion mechanisms regulating the migration of monocytes

    Nat Rev Immunol

    (2004)
  • A.D. Luster et al.

    Immune cell migration in inflammation: present and future therapeutic targets

    Nat Immunol

    (2005)
  • K. Ley et al.

    Getting to the site of inflammation: the leukocyte adhesion cascade updated

    Nat Rev Immunol

    (2007)
  • P. Vajkoczy et al.

    Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis

    J Exp Med

    (2003)
  • T. Lapidot

    Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice. The role of SDF-1/CXCR4 interactions

    Ann N Y Acad Sci

    (2001)
  • D.J. Ceradini et al.

    Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1

    Nat Med

    (2004)
  • J.D. Abbott et al.

    Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury

    Circulation

    (2004)
  • D.H. Walter et al.

    Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease

    Circ Res

    (2005)
  • J. Yamaguchi et al.

    Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization

    Circulation

    (2003)
  • K. Schomig et al.

    Interleukin-8 is associated with circulating CD133+ progenitor cells in acute myocardial infarction

    Eur Heart J

    (2006)

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