Autologous Bone Marrow-Derived Mesenchymal Stromal Cells for the Treatment of Allograft Rejection After Renal Transplantation: Results of a Phase I Study
Marlies E.J. Reinders,Johan W. de Fijter,Helene Roelofs,Ingeborg M. Bajema,Dorottya K. de Vries,Alexander F. Schaapherder,Frans H.J. Claas,Paula P.M.C. van Miert,Dave L. Roelen,Cees van Kooten,Willem E. Fibbe,Ton J. Rabelink +11 more
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TLDR
Autologous BM MSC treatment in transplant recipients with subclinical rejection and IF/TA is clinically feasible and safe, and the findings are suggestive of systemic immunosuppression.Abstract:
Despite excellent short-term results, long-term survival of transplanted kidneys has not improved accordingly. Although alloimmune responses and calcineurin inhibitor-related nephrotoxicity have been identified as main drivers of fibrosis, no effective treatment options have emerged. In this perspective, mesenchymal stromal cells (MSCs) are an interesting candidate because of their immunosuppressive and regenerative properties. Of importance, no other clinical studies have investigated their effects in allograft rejection and fibrosis. We performed a safety and feasibility study in kidney allograft recipients to whom two intravenous infusions (1 million cells per kilogram) of autologous bone marrow (BM) MSCs were given, when a protocol renal biopsy at 4 weeks or 6 months showed signs of rejection and/or an increase in interstitial fibrosis/tubular atrophy (IF/TA). Six patients received MSC infusions. Clinical and immune monitoring was performed up to 24 weeks after MSC infusions. MSCs fulfilled the release criteria, infusions were well-tolerated, and no treatment-related serious adverse events were reported. In two recipients with allograft rejection, we had a clinical indication to perform surveillance biopsies and are able to report on the potential effects of MSCs in rejection. Although maintenance immunosuppression remained unaltered, there was a resolution of tubulitis without IF/TA in both patients. Additionally, three patients developed an opportunistic viral infection, and five of the six patients displayed a donor-specific downregulation of the peripheral blood mononuclear cell proliferation assay, not reported in patients without MSC treatment. Autologous BM MSC treatment in transplant recipients with subclinical rejection and IF/TA is clinically feasible and safe, and the findings are suggestive of systemic immunosuppression.read more
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Stem Cell Therapies in Clinical Trials: Progress and Challenges
TL;DR: Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types and applications are progressing in trials, some with early benefits to patients.
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TL;DR: The preclinical and clinical studies of MSCs from different adult tissues are summarized, the current hurdles to their use are discussed, and the future development of pluripotent stem cell-derived M SCs are proposed as an approach to immunomodulation therapy.
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TL;DR: Current knowledge on cellular and molecular mechanisms involved in MSC-mediated immunomodulation are reviewed and focus on the viability of MSCs, as there is still uncertainty concerning the tumorigenic potential of living M SCs.
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Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis
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References
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Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN').
Kim Solez,Robert B. Colvin,Lorraine C. Racusen,Banu Sis,Philip F. Halloran,Patricia E. Birk,Patricia Campbell,Marilia Cascalho,A. B. Collins,Anthony J. Demetris,Cinthia B. Drachenberg,Ian W. Gibson,Paul C. Grimm,Mark Haas,Evelyne Lerut,Helen Liapis,Roslyn B. Mannon,P. B. Marcus,Michael Mengel,Michael J. Mihatsch,Brian J. Nankivell,Volker Nickeleit,John C. Papadimitriou,Jeffrey L. Platt,Parmjeet Randhawa,Ian Roberts,L. Salinas-Madriga,Daniel R. Salomon,Daniel Serón,M. Sheaff,Jan J. Weening +30 more
TL;DR: The 8th Banff Conference on Allograft Pathology was held in Edmonton, Canada, 15–21 July 2005, and major outcomes included the elimination of the non‐specific term ‘chronic allograft nephropathy’ (CAN) and the recognition of the entity of chronic antibody‐mediated rejection.
Journal ArticleDOI
Mesenchymal Stromal Cells: Current Understanding and Clinical Status†
TL;DR: This review highlights the current understanding into the biology of MSCs with particular emphasis on the cardiovascular and renal applications, and provides a brief update on the clinical status of M SC‐based therapy.
Journal ArticleDOI
Strategies to improve long-term outcomes after renal transplantation.
TL;DR: Current antirejection therapy, including calcineurin blockers such as cyclosporine and tacrolimus, the interleukin-2 signal-transduction inhibitor sirolimus and the purine-synthesis inhibitor mycophenolate mofetil are discussed, which inhibits the proliferation of T cells and B cells.
Journal ArticleDOI
Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study
Marjolijn Duijvestein,Anne Christine W. Vos,Helene Roelofs,Manon E. Wildenberg,Barbara B. Wendrich,H. W. Verspaget,Engelina Maria Christina Kooy-Winkelaar,Frits Koning,Jaap Jan Zwaginga,Herma H. Fidder,Auke P. Verhaar,Willem E. Fibbe,Gijs R. van den Brink,Daniel W. Hommes +13 more
TL;DR: Administration of autologous bone marrow derived MSCs appears safe and feasible in the treatment of refractory Crohn's disease.
Journal ArticleDOI
Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial.
Jianming Tan,Weizhen Wu,Xiumin Xu,Lianming Liao,Feng Zheng,Shari Messinger,Xinhui Sun,Jin Chen,Shunliang Yang,Jinquan Cai,Xia Gao,Antonello Pileggi,Camillo Ricordi +12 more
TL;DR: Among patients undergoing renal transplant, the use of autologous MSCs compared with anti-IL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function at 1 year.