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Mesenchymal Stromal Cells for Graft-Versus-Host Disease

  • Miriam López-Parra
  • Eva M. Villarón
  • Fermín Sánchez-GuijoEmail author
Chapter
Part of the Stem Cells in Clinical Applications book series (SCCA)

Abstract

Graft-versus-host disease (GVHD) remains as one of the most important complications after allogeneic hematopoietic stem cell transplantation (allo-SCT) and there is no definitive second-line therapy for steroid-refractory patients both in acute and chronic GVHD. Mesenchymal stromal cells (MSC) have emerged as an attractive potential therapeutic tool in this setting, based on their potent immunomodulatory capacity. MSC are able to modulate the activation, proliferation, and/or maturation of T-cells, B-cells, NK cells, dendritic cells, neutrophils, etc., and expand the proportion of other immunomodulatory cells (e.g., regulatory T-cells, M2 macrophages) both in vitro and in vivo. All these mechanisms favor their potential application in GVHD, where deregulation of the adoptive and innate immune systems together with a high pro-inflammatory microenvironment induces the typically observed damage in the target organs. In this chapter, we discuss the clinical experience on the use of MSC both for the prevention and treatment of GVHD. The largest experience has been generated in the treatment of steroid-refractory acute GVHD, where MSC have demonstrated in numerous phase II trials relatively high response rates, including complete responses, which correlate with a significant benefit in overall survival. Nevertheless, there are few phase III trial evidences of the beneficial effects of MSC and some reported results have been disappointing. Fortunately, new information is coming from these randomized trials that may lead to additional MSC approvals in some countries, especially for pediatric patients. There are many questions that have not been answered yet, covering the optimal culture and expansion methods, the need of cryopreservation and/or refreshing the cryopreserved products before administration, the best timing, and the number of doses and their intervals, among others, including the need of a biological assay or biomarker that may predict a clinical response to MSC before initiating the treatment.

Keywords

Graft-versus-host disease (GVHD) Mesenchymal stromal cells (MSC) Allogeneic hematopoietic stem cell transplantation 

Abbreviations

GVHD

Graft-versus-host disease

ISCT

International Society for Cellular and Gene Therapy

MSC

Mesenchymal stromal cells

Allo-SCT

Allogeneic hematopoietic stem cell transplantation

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Miriam López-Parra
    • 1
    • 2
    • 3
  • Eva M. Villarón
    • 1
    • 2
    • 3
  • Fermín Sánchez-Guijo
    • 1
    • 2
    • 3
    Email author
  1. 1.Unidad de Terapia Celular y Servicio de HematologiaIBSAL-Hospital Universitario de Salamanca, Universidad de SalamancaPaseo de San VicenteSpain
  2. 2.Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Red TerCel, Instituto de Salud Carlos IIIMadridSpain
  3. 3.Centro de Investigación del CáncerUniversidad de SalamancaSalamancaSpain

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