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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell Dev. Biol. | doi: 10.3389/fcell.2019.00255

Clinical translation of mesenchymal stromal cell therapy for graft versus host disease

 Juliana Godoy1, Raquel Paiva1, Aline Souza1,  Andrea Kondo1, Jose Kutner1 and  Oswaldo K. Okamoto1, 2*
  • 1Department of Hemotherapy and Cell Therapy, Hospital Israelita Albert Einstein, Brazil
  • 2Human Genome and Stem Cell Research Center, Institute of Biosciences, University of São Paulo, Brazil

Graft versus host disease (GVHD) is a common condition in patients subjected to allogeneic hematopoietic stem cell transplantation. The immune cells derived from the grafted stem cells attack recipient’s tissues, including those from the skin, liver, eyes, mouth, lungs, gastrointestinal tract, neuromuscular system and genitourinary tract, may lead to severe morbidity and mortality. Acute GVHD can occur within few weeks after the allogeneic cells have engrafted in the recipient while chronic GVHD may occur any time after transplant, typically within months. Although treatable by systemic corticosteroid administration, effective responses are not achieved for a significant proportion of patients, a condition associated with poor prognosis. The use of multipotent mesenchymal stromal cells (MSCs) as an alternative to treat steroid-refractory GVHD had improved last decade, but the results are still controversial. Some studies have shown improvement in the life quality of patients after MSCs treatment, while others have found no significant benefits. In addition to variations in trial design, discrepancies in protocols for MSCs isolation, characterization, and ex vivo manipulation, account for inconsistent clinical results. In this review, we discuss the immunomodulatory properties supporting the therapeutic use of MSCs in GVHD and contextualize the main clinical findings of recent trials using these cells. Critical parameters for the clinical translation of MSCs, including consistent production of MSCs according to Good Manufacturing Practices (GMPs) and informative potency assays for product quality control, are addressed.

Keywords: Mesenchymal Stromal Cells, Immunomodulation, Graft versus host disease (GVHD), Bone Marrow, Good manufacturing practices

Received: 14 Jun 2019; Accepted: 15 Oct 2019.

Copyright: © 2019 Godoy, Paiva, Souza, Kondo, Kutner and Okamoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Oswaldo K. Okamoto, Department of Hemotherapy and Cell Therapy, Hospital Israelita Albert Einstein, Sâo Paulo, Brazil, keith.okamoto@usp.br