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Review
. 2019 Nov 21:7:255.
doi: 10.3389/fcell.2019.00255. eCollection 2019.

Clinical Translation of Mesenchymal Stromal Cell Therapy for Graft Versus Host Disease

Juliana A P Godoy  1 , Raquel M A Paiva  1 , Aline M Souza  1 , Andrea T Kondo  1 , Jose M Kutner  1 , Oswaldo K Okamoto  1   2
Affiliations
Review

Clinical Translation of Mesenchymal Stromal Cell Therapy for Graft Versus Host Disease

Juliana A P Godoy et al. Front Cell Dev Biol. .

Abstract

Graft versus host disease (GVHD) is a common condition in patients subjected to allogeneic hematopoietic stem cell transplantation (HSCT). 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 (QC), are addressed.

Keywords: bone marrow; good manufacturing practices; graft versus host disease; immunomodulation; mesenchymal stromal cells.

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Figures

FIGURE 1
FIGURE 1
Classification and stage of graft versus host disease (GVHD).
FIGURE 2
FIGURE 2
Immunomodulatory effects of mesenchymal stromal cells (MSC). Mesenchymal stromal cells release several molecules that act directly in cells from the immune system, favoring an anti-inflammatory microenvironment.
FIGURE 3
FIGURE 3
Mesenchymal stromal cells in Clinical Trials. (A) Therapeutic indications being addressed with MSCs. (B) MSCs Clinical Trials classified by Clinical Phase. Data for 181 registered clinical trials with recruiting status.
See this image and copyright information in PMC

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References

    1. Andreas K., Sittinger M., Ringe J. (2014). Toward in situ tissue engineering: chemokine-guided stem cell recruitment. Trends Biotechnol. 32 483–492. 10.1016/j.tibtech.2014.06.008 - DOI - PubMed
    1. Appelbaum F. R. (2001). Hematopoietic cell transplantation as immunotherapy. Nature 411 385–389. - PubMed
    1. Arora M., Cutler C. S., Jagasia M. H., Pidala J., Chai X., Martin P. J., et al. (2016). Late acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol. Blood Marrow Transpl. 22 449–455. 10.1016/j.bbmt.2015.10.018 - DOI - PMC - PubMed
    1. Bader P., Kuçi Z., Bakhtiar S., Basu O., Bug G., Dennis M. (2018). Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM). Bone Marrow Transplant. 53 852–862. 10.1038/s41409-018-0102-z - DOI - PMC - PubMed
    1. Belema-Bedada F., Uchida S., Martire A., Kostin S., Braun T. (2008). Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2. Cell Stem Cell. 5 566–575. 10.1016/j.stem.2008.03.003 - DOI - PubMed

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