Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study

Erpicum, Pauline; Weekers, Laurent; Detry, Olivier; Bonvoisin, Catherine; Delbouille, Marie‐Hélène; Gregoire, Céline; Baudoux, Étienne; Briquet, Alexandra; Lechanteur, Chantal; Maggipinto, Gianni; Somja, Joan; Pottel, Hans; Baron, Frédéric; Jouret, François; Béguin, Yves

doi:10.1016/j.kint.2018.08.046

Cited by 91 publications

(122 citation statements)

References 95 publications

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“…In addition, kidneys treated with the hydrogen gas-containing organ preservation solution still developed severe acute tubulointerstitial injury. However, it is possible that the combination of hydrogen-containing organ preservation solution with an intraoperative rinse [31], intraoperative or postoperative immunosuppressant therapy, or adjuvant cell therapy using cells such as mesenchymal stromal cells [32,33] could allow kidneys from marginal donors that have not been usable to be transplanted in the future.…”

Section: Discussionmentioning

confidence: 99%

Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs

Kobayashi

Sano

2019

PLoS ONE

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Various methods have been devised to dissolve hydrogen gas in organ preservation solutions, including use of a hydrogen gas cylinder, electrolysis, or a hydrogen-generating agent. However, these methods require considerable time and effort for preparation. We investigated a practical technique for rapidly dissolving hydrogen gas in organ preservation solutions by using a canister containing hydrogen-absorbing alloy. The efficacy of hydrogen-containing organ preservation solution created by this method was tested in a miniature pig model of kidney transplantation from donors with circulatory arrest. The time required for dissolution of hydrogen gas was only 2-3 minutes. When hydrogen gas was infused into a bag containing cold ETK organ preservation solution at a pressure of 0.06 MPa and the bag was subsequently opened to the air, the dissolved hydrogen concentration remained at 1.0 mg/L or more for 4 hours. After warm ischemic injury was induced by circulatory arrest for 30 minutes, donor kidneys were harvested and perfused for 5 minutes with hydrogen-containing cold ETK solution or hydrogen-free cold ETK solution. The perfusion rate was faster from the initial stage with hydrogen-containing cold ETK solution than with hydrogen-free ETK solution. After storage of the kidney in hydrogen-free preservation solution for 1 hour before transplantation, no urine production was observed and blood flow was not detected in the transplanted kidney at sacrifice on postoperative day 6. In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting where organs are removed from donors.

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Section: Discussionmentioning

confidence: 99%

Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs

Kobayashi

Sano

2019

PLoS ONE

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“…Nonetheless, a substantial number of completed and ongoing clinical trials and in vivo studies of MSCs for immune‐mediated diseases and transplants have been based, at least in part, on the premise that MSCs increase the frequency of T‐reg following systemic or localized administration. As summarized in Table , immune profiling studies from clinical trials involving relatively limited numbers of patients with transplants or immune‐mediated disease have provided preliminary evidence for increased T‐reg numbers or proportions following systemic or localized MSC administration . The last few years have also witnessed swift progress in the number of clinical trials aimed at assessing the safety, feasibility, and efficacy of ex vivo‐expanded T‐reg in transplantation and efforts have begun to translate this therapy to the clinic .…”

Section: Conclusion: Knowledge Gaps and The Potential For Clinical Trmentioning

confidence: 99%

Effects of mesenchymal stromal cells on regulatory T cells: Current understanding and clinical relevance

Negi

Griffin

2020

Stem Cells

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The immunomodulatory potential of mesenchymal stromal cells (MSCs) and regulatory T cells (T-reg) is well recognized by translational scientists in the field of regenerative medicine and cellular therapies. A wide range of preclinical studies as well as a limited number of human clinical trials of MSC therapies have not only shown promising safety and efficacy profiles but have also revealed changes in T-reg frequency and function.However, the mechanisms underlying this potentially important observation are not well understood and, consequently, the optimal strategies for harnessing MSC/T-reg cross-talk remain elusive. Cell-to-cell contact, production of soluble factors, reprogramming of antigen presenting cells to tolerogenic phenotypes, and induction of extracellular vesicles ("exosomes") have emerged as possible mechanisms by which MSCs produce an immune-modulatory milieu for T-reg expansion. Additionally, these two cell types have the potential to complement each other's immunoregulatory functions, and a combinatorial approach may exert synergistic effects for the treatment of immunological diseases. In this review, we critically assess recent translational research related to the outcomes and mechanistic basis of MSC effects on T-reg and provide a perspective on the potential for this knowledge base to be further exploited for the treatment of autoimmune disorders and transplants.

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“…Besides, one study was an reanalysis of a former study, two studies reported the outcomes of co-fusion MSCs together with other stem cells and one study did not intend to inject MSCs as induction therapy. At last, four trials consisted of ve cohorts which were Pan group, Sun group, Tan low-dose CNIs group and Tan standard-dose CNIs group [12][13][14][15] , with a total of 301 patients, were included in this analysis ( Fig. 1).…”

Section: Included Studiesmentioning

confidence: 99%

“…During last decade, MSCs has been performed as induction therapy in some kidney transplantation patients, but the results are controversial. Some researches demonstrated the bene cial effects of MSCs treatment in decreasing the ratio of memory/effector CD8(+) T cells, promoting faster renal function recovery or reducing incidence of opportunistic infections [11][12][13] . Whereas, others suggested MSCs were not advantage over traditional regimens [14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Induction Therapy With Mesenchymal Stem Cells in Kidney Transplantation: A Meta-Analysis

Zhao¹,

Han

et al. 2020

Preprint

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Objective The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stem cells (MSCs) versus other regimens as induction therapy in kidney transplantation patients.Methods PubMed, Embase, EBSCO, Ovid and the Cochrane Library were searched to identify prospective clinical trials which compared MSCs with other regimens as induction therapy in renal allograft.Results Four studies with five cohorts were contained, including a total of 301 patients. The pooled results revealed that the MSCs therapy had a lower 1-year infection rate (RR=0.73, 95% CI: 0.58–0.93, P=0.01), espeicially for 1-year opportunistic infection rate (RR=0.59, 95% CI: 0.37–0.93, P=0.02). There were no significant differences between the two protocols regarding 1-year acute rejection (AR) rate (RR=0.69, 95% CI: 0.42–1.14, P=0.15), 1-year graft survival rate (RR=0.99, 95% CI: 0.95–1.03, P=0.74), delayed graft function (DGF) rate (RR=0.72, 95% CI: 0.34–1.50, P=0.38) and renal graft function at 1 month (MD=2.4, 95% CI: -7.41– 12.22, p=0.63), 3 months (MD=0.91, 95% CI: -4.17– 5.98, p=0.73), 6 months (MD=-1.41, 95% CI: -5.69– 2.87, p=0.52), 12 months (MD=1.25, 95% CI: -3.89– 6.4, p=0.63) post surgery. Subgroup analysis demonstrated 1-year AR rate, DGF rate and renal graft function at 12 month post surgery did not reach to a significant difference between low-dose calcineurin inhibitors (CNIs) group with standard-dose CNIs group, indicating successful CNIs withdrawal in combination with MSCs treatment. Meanwhile, when applied MSCs as an alternative standard induction therapy regimen, all of those outcomes mentioned above were also comparable with those in MSCs plus standard induction therapy group.Conclusion Induction therapy of MSCs has similar inducing immune tolerance effects on the recipients in kidney transplantation compared with that of other regimens. However, regarding the long term effect, as represented by 1-year infection rate, 1-year opportunistic infection rate and CNIs withdrawl, MSCs therapy has a significant advantage.

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Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study

Cited by 91 publications

References 95 publications

Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs

Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs

Effects of mesenchymal stromal cells on regulatory T cells: Current understanding and clinical relevance

Induction Therapy With Mesenchymal Stem Cells in Kidney Transplantation: A Meta-Analysis

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