Long-Term Clinical and Immunological Profile of Kidney Transplant Patients Given Mesenchymal Stromal Cell...

Area of Science:

• Immunology
• Regenerative Medicine
• Transplantation

Background:

• Living-donor kidney transplantation requires long-term immunosuppression to prevent rejection.
• Mesenchymal stromal cells (MSCs) are being investigated for their immunomodulatory properties in transplantation.
• Phase 1 studies assess the safety and feasibility of novel cell therapies.

Purpose of the Study:

• To evaluate the long-term clinical and immunological outcomes of kidney transplant recipients treated with autologous bone marrow-derived MSCs.
• To assess the safety and feasibility of MSC therapy in the context of kidney transplantation.
• To explore the potential of MSCs to induce immune tolerance and enable immunosuppression withdrawal.

Main Methods:

• A phase 1 clinical study involving four living-donor kidney transplant patients receiving autologous MSCs.
• Patients received MSCs at different time points (day 7 posttransplant or day -1 pretransplant).
• Immunological monitoring included assessment of T cell populations, B cell levels, and ex vivo cytotoxicity.

Main Results:

• All MSC-treated patients demonstrated stable graft function over 5-7 years with no increased risk of infections or neoplasms.
• MSC recipients showed reduced circulating memory CD8+ T cells and donor-specific cytotoxicity compared to controls.
• Two patients exhibited increased regulatory T cell/CD8+ T cell ratios and higher levels of naive and transitional B cells, with one patient successfully withdrawing ciclosporin.

Conclusions:

• Autologous MSC therapy is safe and well-tolerated long-term in kidney transplant recipients.
• MSC treatment may induce a pro-tolerogenic immune environment, potentially facilitating immunosuppressive drug withdrawal.
• Extensive immunomonitoring is crucial for selecting kidney transplant recipients who may benefit from MSC therapy and subsequent immunosuppression reduction.