Treatment with mesenchymal stromal cells is a risk factor for pneumonia‐related death after allogeneic hematopoietic stem cell transplantation

Forslöw, Ulrica; Blennow, Ola; LeBlanc, Katarina; Ringdén, Olle; Gustafsson, Britt; Mattsson, Jonas; Remberger, Mats

doi:10.1111/j.1600-0609.2012.01824.x

Cited by 72 publications

(64 citation statements)

References 27 publications

(28 reference statements)

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“…For example, short-course immunosuppression, which has shown promise in preventing GvHD 89 and prolonging liver allograft survival 90,91 , may be sufficient to extend persistence of MSCs and augment their therapeutic effect. In addition, antibody-mediated depletion of immune cells such as NK or cytotoxic lymphocytes may prolong MSC persistence; however, such strategies could also increase the risk of infection in vulnerable patient populations 92 .…”

Section: Strategies To Prolong Msc Persistencementioning

confidence: 99%

Mesenchymal stem cells: immune evasive, not immune privileged

2014

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The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or ‘immune privileged’; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-the-shelf therapies consisting of MSCs grown in culture. However, recent studies describing generation of antibodies against and immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be immune privileged. Nevertheless, whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known, and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief ‘hit and run’ mechanism, protecting MSCs from immune detection and prolonging their persistence in vivo may improve clinical outcomes and prevent patient sensitization toward donor antigens.

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Section: Strategies To Prolong Msc Persistencementioning

confidence: 99%

Mesenchymal stem cells: immune evasive, not immune privileged

2014

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“…17 Antifungal, antibacterial and Pneumocystis jiroveci prophylaxis was given as previously described. 18 Serum analysis…”

Section: Prophylaxis and Surveillancementioning

confidence: 99%

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Bahr

Blennow

Alm

et al. 2015

Bone Marrow Transplant

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Vitamin D has emerged as a central player in the immune system, with its deficiency being implicated in the pathogenesis of several autoimmune diseases, including chronic GvHD. This is a retrospective cohort analysis of 166 patients, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the Karolinska University Hospital, evaluating GvHD, graft failure, infectious complications and survival after HSCT in relation to pre-transplantation vitamin D levels. Most of the patients were deficient in vitamin D before HSCT (median 42 nmol/L). In multivariate analysis, vitamin D level before HSCT was identified as a significant independent risk factor for development of cGvHD. The increased incidence of cGvHD was not coupled to better disease-free survival; instead there was a trend towards lower overall survival in the vitamin D-deficient patients. In addition, we found a significant correlation between vitamin D deficiency and incidence of CMV disease, with no case of CMV disease occurring in patients with sufficient levels of vitamin D before HSCT. Our results support a role of vitamin D in immune tolerance following HSCT. These findings could be highly relevant for the care of HSCT patients, and prospective, randomized studies on the effect of vitamin D supplementation are therefore needed.

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“…On the other hand, Forslow et al, in a retrospective study, found that treatment with MSCs may be a risk factor for pneumonia-related mortality after allo-HSCT [76]. Moreover, MSCs co-transplanted with HSCs seem to increase the risk of relapse in patients with hematological malignancies, as reported by Ning et al [77].…”

Section: Clinical Applications Of Mscs In Allo-hsct and Gvhdmentioning

confidence: 99%

Mesenchymal Stem Cell Derived Extracellular Vesicles: A Role in Hematopoietic Transplantation?

Luca

Trino

Laurenzana

et al. 2017

IJMS

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Mesenchymal stem cells (MSCs) are a heterogeneous cellular population containing different progenitors able to repair tissues, support hematopoiesis, and modulate immune and inflammatory responses. Several clinical trials have used MSCs in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent hematopoietic stem cell (HSC) engraftment failure, reduce aplasia post chemotherapy, and to control graft versus host disease (GvHD). The efficacy of MSCs is linked to their immune suppressive and anti-inflammatory properties primarily due to the release of soluble factors. Recent studies indicate that most of these effects are mediated by extracellular vesicles (EVs). MSC-EVs have therefore therapeutic effects in regenerative medicine, tumor inhibition, and immune-regulation. MSC-EVs may offer specific advantages for patient safety, such as lower propensity to trigger innate and adaptive immune responses. It has been also shown that MSC-EVs can prevent or treat acute-GvHD by modulating the immune-response and, combined with HSCs, may contribute to the hematopoietic microenvironment reconstitution. Finally, MSC-EVs may provide a new potential therapeutic option (e.g., transplantation, gene therapy) for different diseases, particularly hematological malignancies. In this review, we will describe MSC and MSC-EVs role in improving allo-HSCT procedures and in treating GvHD.

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Treatment with mesenchymal stromal cells is a risk factor for pneumonia‐related death after allogeneic hematopoietic stem cell transplantation

Cited by 72 publications

References 27 publications

Mesenchymal stem cells: immune evasive, not immune privileged

Mesenchymal stem cells: immune evasive, not immune privileged

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Mesenchymal Stem Cell Derived Extracellular Vesicles: A Role in Hematopoietic Transplantation?

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