Safety and Efficacy of MCA-derived Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients: The Nereid Study*

General Information

Summary Background summary Kidney transplantation has improved survival and quality of life for patients with end-stage renal disease. However, despite advances in immunosuppressive therapy, long- term allograft survival outcomes have not improved over the last decade. There is a clear need for therapeutic alternatives because 1) patients may not respond to existing therapeutic choices, 2) they do not show an improvement of the fibrosis reaction 3) they do not show an effect on long term survival, 4) they may develop immunosuppression induced serious (sometimes fatal) side effects and toxicities. LUMC has conducted 3 trials using bone-marrow derived mesenchymal stromal cells (BM-MSC) showing both safety and efficacy of their use in the setting of kidney transplantation. MSC isolation and culture from both autologous and allogeneic sources is being hampered by cellular heterogeneity and replicative senescence. Generation of MSC from induced pluripotent stem cells (iPSC) so called MCA-derived MSC may circumvent these limitations. MCA-derived MSC have recently been tested in clinical trials and found to be safe and more cost effective than traditional MSC. Given the benefits of MCA-erived MSC we propose to test whether MCA-derived MSC are safe in the setting of kidney transplantation in a clinical study. The TRITON study in which MSC therapy was shown to allow withdrawal of the nephrotoxic calcineurin inhibitor tacrolimus, will form the backbone for this clinical trial in which 16 patients will receive MCA-derived MSC combined with tacrolimus reduction to study safety and immunological efficacy of MCA-derived MSC therapy.
Clinical trials phase Phases 1/2
Start date (estimated) 2023-07-01
Clinical feature
Label kidney disease
Link http://purl.obolibrary.org/obo/DOID_557
Description A urinary system disease that is located_in the kidney.

Administrative Information

ICTRP weblink https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON53310
EudraCT number 2022-004168-11-NL
Other study identifiers
Name NL83484.000.22
Description CCMO (Centrale Commissie Mensgebonden Onderzoek, CCMO)
Source weblink https://onderzoekmetmensen.nl/en/trial/53310
Public contact
Email info@lumc.nl
Public email info@lumc.nl
First name N. N.
Last name N. N.
Country
Netherlands
Address freetext Albinusdreef 2 2333ZA Leiden NL

Cells

Which differentiated cell type is used
Label mesenchymal stem cell
Link http://purl.obolibrary.org/obo/CL_0000134
Description A connective tissue cell that normally gives rise to other cells that are organized as three-dimensional masses. In humans, this cell type is CD73-positive, CD90-positive, CD105-positive, CD45-negative, CD34-negative, and MHCII-negative. They may further differentiate into osteoblasts, adipocytes, myocytes, neurons, or chondroblasts in vitro. Originally described as residing in the bone marrow, this cell type is now known to reside in many, if not all, adult organs.; Many but not all mesenchymal cells derive from the mesoderm. MSCs are reportedly CD3-negative, CD4-negative, CD5-negative, CD8-negative, CD11a-negative, CD11b-negative, CD14-negative, CD19-negative, CD29-positive, CD31-negative, CD34-negative, CD38-negative, CD40-negative, CD44-positive, CD45-negative, CD49-positive, CD54-positive, CD66b-negative, CD79a-negative, CD80-negative, CD102-positive, CD106-positive, CD117-positive, CD121a-positive, CD121b-positive, CD123-positive, CD124-positive, CD133-negative, CD146-positive, CD166-positive, CD271-positive, B220-negative, Gr1-negative, MHCI-positive, MHCII-negative, SSEA4-negative, sca1-positive, Ter119-negative, and glycophorin A-negative. Cultured MSCs are capable of producing stem cell factor, IL7, IL8, IL11, TGF-beta, cofilin, galectin-1, laminin-receptor 1, cyclophilin A, and MMP-2.

Recruitment

Recruitment Status Not yet recruiting
Comment recruitment status Recruitment Status: Pending
Estimated number of participants 16