Mesenchymal stem cells transplantation during ex vivo lung perfusion

Mesenchymal stem cells transplantation during ex vivo lung perfusion

Author’s Accepted Manuscript Mesenchymal stem cells transplantation during ex vivo lung perfusion Mohamed S.A. Mohamed http://www.jhltonline.org PII...

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Author’s Accepted Manuscript Mesenchymal stem cells transplantation during ex vivo lung perfusion Mohamed S.A. Mohamed

http://www.jhltonline.org

PII: DOI: Reference:

S1053-2498(16)30385-0 http://dx.doi.org/10.1016/j.healun.2016.10.010 HEALUN6390

To appear in: Journal of Heart and Lung Transplantation Cite this article as: Mohamed S.A. Mohamed, Mesenchymal stem cells transplantation during ex vivo lung perfusion, Journal of Heart and Lung Transplantation, http://dx.doi.org/10.1016/j.healun.2016.10.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Mesenchymal Stem Cells Transplantation During Ex Vivo Lung Perfusion Mohamed S. A. Mohamed; MBBCh, MSc, MD. From University of Cologne, Deutz-Kalker Str. 118, 50679, Cologne. Email: [email protected]

Key words: Cell therapy; Ex vivo lung perfusion; Lung preservation; Lung transplantation; Mesenchymal stem cells

Comment on: Mordant P, Nakajima D, Kalaf R, et al. Mesenchymal stem cell treatment is associated with decreased perfusate concentration of interleukin-8 during ex vivo perfusion of donor lungs after 18hour preservation. J Heart Lung Transplant. 2016 May 6. pii: S1053-2498(16)30121-8. doi: 10.1016/j.healun.2016.04.017. [Epub ahead of print]

Malignant development in Mesenchymal Stem Cells (MSCs) is a distinct possibility, especially with immunosuppression for lung transplant (1). In the addressed study, (2) the authors used Human Umbilical Cord Perivascular MSCs (HUCPVMSCs), which might have a higher risk of malignant development than Bone Marrow MSCs (BMMSCs). In a previous report, the proliferative potential of HUCPVMSCs was compared to that of BMMSCs. The results showed initial similar rates of proliferation. However, between days 7 and 14, the HUCPVMSCs had higher proliferation rate, and beyond day 20 BMMSCs responded to contact inhibition and stopped proliferation, while HUCPVMSCs continued to proliferate resulting in multilayering (3). In the addressed study, the MSCs were subjected to cryopreservation. This procedure might have a negative impact on the genetic materials of the cells without change in viability. The transcriptome of the cryopreserved human embryonic stem cells is not initially different than those of the control non-frozen cells. However, a differential genetic transcription at late time points has been reported (4). Accordingly, the use of freshly isolated cells might be favored. MSCs secrete many mediators that modulate the immune response and can be involved in the attenuation of the ischemic reperfusion injury (IRI), including IL10 (5). IL10 has been reported to significantly suppress the production of IL8 in a dose dependent manner. Accordingly, this might contribute to the mechanism of the reported IL8 suppression, but anticipates a possibility towards higher IL10 level in the MSCs treated group, which is not the case in the presented results. Moreover, MSCs were introduced after one hour of ex vivo lung perfusion (EVLP) and the results of the addressed study show the levels of IL8 of the study group lower than those of the control group, starting from 0h, MSCs adminstration (Figure 6d of the addressed study) (2), which may not allow enough time for action of MSCs. As the mechanism of action of MSCs to attenuate the IRI relies mainly on the secreted mediators, time is required. In the addressed study the duration of EVLP was 12 hours, which could be enough for graft conditioning and the effective secretion of mediators by MSCs. In the usual clinical practice, EVLP may be performed for an average of 4 hours, which might not be enough for the effective secretion of mediators by MSCs. Accordingly, it might be favored that the cells are cultured till 90% confluence, where enough soluble mediators are available in the used culture medium, before transplant. The technique of EVLP-MSCs transplant should be considered in the surgical practice of lung transplant, however, the above remarks should be well investigated before the clinical application.

Conflicts of interest No funding was provided for the development of this work.

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