Human leukocyte antigen selected allogeneic mesenchymal stromal cell therapy in renal transplantation: The Neptune study, a phase I single-center study

Dreyer, G.; Groeneweg, Koen E.; Heidt, Sebastiaan; Roelen, Dave L.; Pel, Melissa van; Roelofs, Helene; Huurman, Volkert A. L.; Bajema, Ingeborg M.; Moes, Dirk Jan A R; Fibbe, Willem E.; Claas, Frans H.J.; Kooten, Cees van; Rabelink, Rabelink J; Fijter, Johan W. de; Reinders, Marlies E.J.

doi:10.1111/ajt.15910

Cited by 38 publications

(56 citation statements)

References 31 publications

(68 reference statements)

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“…The development of anti‐HLA antibodies was not reported in a recent study where HLA selected allogeneic MSC were infused with low‐dose tacrolimus [39]. This design was proven to be safe with a follow‐up of 1 year after transplantation [40]. In this study, no major alterations in T‐ and B‐cell populations or plasma cytokines were observed upon MSC infusions.…”

Section: Mesenchymal Stromal Cell Therapiesmentioning

confidence: 62%

“…It is advised to document the (serious) adverse events (SAE) according to MedDRA ® (Medical Dictionary for Regulatory Activities), which is the international medical terminology developed under the auspices of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. This method has been used in two recently published trials with cell therapy in renal transplantation and allows for comparison between trials [40,58]. Since the development of infections and malignancies may take time, long‐term follow‐up of patients is required after finalizing clinical trials.…”

Section: Endpoints and Monitoring Of Cellular Therapiesmentioning

confidence: 99%

“…However, allogeneic cells can induce alloimmune responses [38], which might increase the risk for allograft rejection and graft dysfunction. Therefore, in trials with allogeneic cells, analysis of anti‐human leucocyte antigen‐specific antibodies related to allogenic MSC infusions should be performed [40].…”

Section: Endpoints and Monitoring Of Cellular Therapiesmentioning

confidence: 99%

“…The ONE Study consortium developed a standardized method, which monitors the general immune response and T‐cell, B‐cell and dendritic cell subsets [70]. This method has been used in the ONE Study, as well as in studies with MSC therapy after renal transplantation [26,40,58]. In addition, functional assays, such as the in vitro ‐mixed lymphocyte reaction and measurement of cytokines, might give mechanistic insight after cell therapy [106].…”

Section: Endpoints and Monitoring Of Cellular Therapiesmentioning

confidence: 99%

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Cellular therapies in organ transplantation

et al. 2021

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Summary Cellular therapy is a promising tool for improving the outcome of organ transplantation. Various cell types with different immunoregulatory and regenerative properties may find application for specific transplant rejection or injury‐related indications. The current era is crucial for the development of cellular therapies. Preclinical models have demonstrated the feasibility of efficacious cell therapy in transplantation, early clinical trials have shown safety of several of these therapies, and the first steps towards efficacy studies in humans have been made. In this review, we address the current state of the art of cellular therapies in clinical transplantation and discuss monitoring tools and endpoints for these studies.

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Section: Mesenchymal Stromal Cell Therapiesmentioning

confidence: 62%

Section: Endpoints and Monitoring Of Cellular Therapiesmentioning

confidence: 99%

Section: Endpoints and Monitoring Of Cellular Therapiesmentioning

confidence: 99%

Section: Endpoints and Monitoring Of Cellular Therapiesmentioning

confidence: 99%

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Cellular therapies in organ transplantation

et al. 2021

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“…For example, hBMMSC-EVs revealed significant improvements in patients suffering from refractory graft-versus-host disease [ 179 ]. In another study, administration of hUCMSC-EVs resulted in overall improvement in patients with grade III-IV chronic kidney disease [ 180 ]. Nassar et al conducted a clinical trial to assess the effects of hUCMSC-EVs on pancreatic islet beta cell mass in Type-1 diabetic patients (NCT02138331).…”

Section: Attempts To Improve the Therapeutic Outcomes Of Mscsmentioning

confidence: 99%

Challenges and advances in clinical applications of mesenchymal stromal cells

et al. 2021

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Mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.

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Infusion of Allogeneic Mesenchymal Stromal Cells After Liver Transplantation: A 5‐Year Follow‐Up

et al. 2021

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Various properties of mesenchymal stromal cells (MSCs) might be particularly of interest after liver transplantation (LT). In this article, we report the long‐term results of a prospective, controlled, and first‐in‐human phase 1 study evaluating the safety of a single MSC infusion after LT. A total of 10 LT recipients treated with standard immunosuppression received 1.5 to 3 × 106/kg third‐party unrelated MSCs on postoperative day 3 and were prospectively compared with a control group of 10 LT recipients. Primary endpoints were set to prospectively detect potentially delayed adverse effects of MSC infusion, particularly the occurrence of infections and cancers. Secondary endpoints of liver graft and patient survival, graft rejection and function, occurrence of bile duct complications, and development of donor‐specific anti–human leukocyte antigen (HLA) antibodies (DSA) against liver or MSC donors were studied. The median follow‐up was 85 months. There was no difference in overall rates of infection or cancer at 5 years of follow‐up between the 2 groups. There was also no difference in secondary endpoints. The prevalence of de novo liver DSAs related to HLA mismatches was twice as high in the MSC group compared with the control group. All of the de novo class II HLA antibodies against MSCs were linked to a shared HLA mismatch between the liver and MSCs. This study confirms the safety of a single MSC infusion after LT. The potential benefits of MSC injections in the context of organ transplantation have yet to be demonstrated by larger prospective studies. The development of anti‐HLA antibodies against an MSC donor should be further evaluated, especially in cases of shared HLA mismatches between graft and MSC donors, despite the fact that no deleterious effect has been detected.

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Human leukocyte antigen selected allogeneic mesenchymal stromal cell therapy in renal transplantation: The Neptune study, a phase I single-center study

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial 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 38 publications

References 31 publications

Cellular therapies in organ transplantation

Cellular therapies in organ transplantation

Challenges and advances in clinical applications of mesenchymal stromal cells

Infusion of Allogeneic Mesenchymal Stromal Cells After Liver Transplantation: A 5‐Year Follow‐Up

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