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

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.; Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts, chondrocytes, myocytes, and adipocytes. These cells originate mainly from the mesoderm of the embryo, which forms connective tissues, muscle, and the circulatory and urinary systems. However, in adults, MSCs are found in multiple tissues, including bone marrow, adipose tissue, the umbilical cord, and dental tissues. The primary function of MSCs is to maintain and repair the tissues in which they are found. When damage occurs, the MSCs are able to migrate to the site of injury, where they aid in regenerating the damaged tissue by differentiating into the required cell type and by secreting growth factors that enhance tissue repair and reduce inflammation. Furthermore, MSCs can also act as immunomodulators, suppressing immune reactions and reducing inflammation, both locally and systemically. Apart from their role in tissue maintenance and repair, MSCs are integral to the field of regenerative medicine and are being investigated for their therapeutic potential in various clinical settings. Owing to their multipotent nature, immunomodulatory activity, and the relative ease of isolation, these cells can be engineered and translated into therapies to treat a variety of diseases, including bone and cartilage defects, liver diseases, heart disorders, and autoimmune diseases, amongst others. They have also been used as vectors for anticancer agents and in cell and gene therapy applications. (This extended description was generated by ChatGPT and reviewed by the CellGuide team, who added references, and by the CL editors, who approved it for inclusion in CL. It may contain information that applies only to some subtypes and species, and so should not be considered definitional.); 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