Autologous bone marrow-derived mesenchymal stromal cell therapy with early tacrolimus withdrawal: The randomized prospective, single-center, open-label TRITON study

Reinders, Marlies E.J.; Groeneweg, Koen E.; Hendriks, Sanne H.; Bank, J.; Dreyer, G.; Vries, Aiko P. J. de; Pel, Melissa van; Roelofs, Helene; Huurman, Volkert A. L.; Meij, Paula; Moes, Dirk Jan A R; Fibbe, Willem E.; Claas, Frans H.J.; Roelen, Dave L.; Kooten, Cees van; Kers, Jesper; Heidt, Sebastiaan; Rabelink, Ton J.; Fijter, Johan W. de

doi:10.1111/ajt.16528

Cited by 28 publications

(56 citation statements)

References 30 publications

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“…A number of clinical trials have been designed to evaluate the safety and efficacy of MSC-based therapy and some good results have been observed in acute kidney injury trials ( 179 ). Very recently, the TRITON study ( 180 ) has used the infusion of autologous MSCs in 29 kidney transplant recipients to withdraw CNI. After 24 weeks of follow up, no differences were observed in graft function, acute rejection, graft loss, major adverse events or in kidney fibrosis.…”

Section: The Reparation Mechanismsmentioning

confidence: 99%

Chronic Kidney Allograft Disease: New Concepts and Opportunities

et al. 2021

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Chronic kidney disease (CKD) is increasing in most countries and kidney transplantation is the best option for those patients requiring renal replacement therapy. Therefore, there is a significant number of patients living with a functioning kidney allograft. However, progressive kidney allograft functional deterioration remains unchanged despite of major advances in the field. After the first post-transplant year, it has been estimated that this chronic allograft damage may cause a 5% graft loss per year. Most studies focused on mechanisms of kidney graft damage, especially on ischemia-reperfusion injury, alloimmunity, nephrotoxicity, infection and disease recurrence. Thus, therapeutic interventions focus on those modifiable factors associated with chronic kidney allograft disease (CKaD). There are strategies to reduce ischemia-reperfusion injury, to improve the immunologic risk stratification and monitoring, to reduce calcineurin-inhibitor exposure and to identify recurrence of primary renal disease early. On the other hand, control of risk factors for chronic disease progression are particularly relevant as kidney transplantation is inherently associated with renal mass reduction. However, despite progress in pathophysiology and interventions, clinical advances in terms of long-term kidney allograft survival have been subtle. New approaches are needed and probably a holistic view can help. Chronic kidney allograft deterioration is probably the consequence of damage from various etiologies but can be attenuated by kidney repair mechanisms. Thus, besides immunological and other mechanisms of damage, the intrinsic repair kidney graft capacity should be considered to generate new hypothesis and potential therapeutic targets. In this review, the critical risk factors that define CKaD will be discussed but also how the renal mechanisms of regeneration could contribute to a change chronic kidney allograft disease paradigm.

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Section: The Reparation Mechanismsmentioning

confidence: 99%

Chronic Kidney Allograft Disease: New Concepts and Opportunities

et al. 2021

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“…On the other hand, Tan et al reported that MSC administration enabled lower dose of calcineurin inhibitor (CNI) immunosuppressants, without compromising graft function or acute rejection occurrence [ 21 ]. Reinders et al recently demonstrated that MSCs infused at 6 and 7 weeks after kidney transplantation allowed the withdrawal of tacrolimus without deterioration in graft function or increase in rejection rates [ 22 ]. Although these data provided a great promise for the application of MSCs as cellular therapeutics to improve the allotransplantation outcomes, discrepancies between studies imply the scope for optimization, which can be considered in the process of MSC preparation and administration.…”

Section: Mscs In Allotransplantation and Limitationsmentioning

confidence: 99%

Preconditioned Mesenchymal Stromal Cells to Improve Allotransplantation Outcome

Cheng

Anggelia

Lin

et al. 2021

Cells

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Mesenchymal stromal cells (MSCs) are tissue-derived progenitor cells with immunomodulatory as well as multilineage differentiation capacities, and have been widely applied as cellular therapeutics in different disease systems in both preclinical models and clinical studies. Although many studies have applied MSCs in different types of allotransplantation, the efficacy varies. It has been demonstrated that preconditioning MSCs prior to in vivo administration may enhance their efficacy. In the field of organ/tissue allotransplantation, many recent studies have shown that preconditioning of MSCs with (1) pretreatment with bioactive factors or reagents such as cytokines, or (2) specific gene transfection, could prolong allotransplant survival and improve allotransplant function. Herein, we review these preconditioning strategies and discuss potential directions for further improvement.

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“…Cell therapy in organ transplantation is an emerging field. Recent clinical trials have mainly focused on the early stage of transplantation, in order to decrease the burden of immunosuppressive agents or induce organ tolerance [10][11][12][13]. Mesenchymal stromal cells (MSCs) are currently the most evaluated cell type and the closest to being used in routine clinical practice.…”

Section: Mesenchymal Stromal Cells To Slow Down Fibrosismentioning

confidence: 99%

“…The two subsequent recipients were infused with MSCs before KTx (2.0 9 10 6 cells/kg), without any consequent inflammatory infiltrates in the kidney graft [15]. Two recent trials, the TRITON study [13] and the NEP-TUNE study [16] tested another approach, i.e. a delayed infusion of MSCs after several weeks post-KTx.…”

Section: Mesenchymal Stromal Cells To Slow Down Fibrosismentioning

confidence: 99%

Pushing the boundaries of organs before it’s too late: pre‐emptive regeneration

Maanaoui

Kerr–Conte

2021

Transpl Int

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Solid organ transplantation is marked by accelerated aging and inexorable fibrosis. It is crucial to promote strategies to attenuate, or to reverse, damage before organ failure. Hence, the objective of this article is to provide insight into strategies, which aim to regenerate or rejuvenate the transplanted organs. Cell therapy with mesenchymal stromal cells is currently under investigation because of their antifibrotic properties. Their ability to promote mitochondrial biogenesis, and to transfer mitochondria to wounded cells, is another approach to boost the organ regeneration. Other teams have investigated bioengineered organs, which consists of decellularization of the damaged organ followed by recellularization. Lastly, the development of CAR-T cell-based technologies may revolutionize the field of transplantation, as recent preclinical studies showed that CAR-T cells could efficiently clear senescent cells from an organ and reverse fibrosis. Ultimately, these cutting-edge strategies may bring the holy grail of a preemptive regenerated organ closer to reality.

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Autologous bone marrow-derived mesenchymal stromal cell therapy with early tacrolimus withdrawal: The randomized prospective, single-center, open-label TRITON study

Abstract: This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 28 publications

References 30 publications

Chronic Kidney Allograft Disease: New Concepts and Opportunities

Chronic Kidney Allograft Disease: New Concepts and Opportunities

Preconditioned Mesenchymal Stromal Cells to Improve Allotransplantation Outcome

Pushing the boundaries of organs before it’s too late: pre‐emptive regeneration

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