Clinical Translation of Mesenchymal Stromal Cell Therapies in Nephrology

Abstract

Mesenchymal stromal cells have emerged as potential candidates for cell-based therapies to modulate the immune response in organ transplantation and repair tissues after acute or chronic injury. Preclinical studies have shown convincingly in rodent models that mesenchymal stromal cells can prolong solid organ graft survival and that they can induce immune tolerance, accelerate recovery from AKI, and promote functional improvement in chronic nephropathies. Multiple complex properties of the cells, including immunomodulatory, anti-inflammatory, and proregenerative effects, seem to contribute. The promising preclinical studies have encouraged investigators to explore the safety, tolerability, and efficacy of mesenchymal stromal cell-based therapy in pilot clinical trials, including those for bone marrow and solid organ transplantation, autoimmune diseases, and tissue and organ repair. Here, we review the available data on culture-expanded mesenchymal stromal cells tested in renal transplantation, AKI, and CKD. We also briefly discuss the relevant issues that must be addressed to ensure rigorous assessment of the safety and efficacy of mesenchymal stromal cell therapies to allow the translation of this research into the practice of clinical nephrology.

Paracrine Proangiogenic Function of Human Bone Marrow-Derived Mesenchymal Stem Cells Is Not Affected by Chronic Kidney Disease

“…Bone marrow-(BM-) derived mesenchymal stromal cells (MSCs) have potent antifibrotic, proangiogenic, and immunomodulatory properties, which makes BM MSC-based therapy for CKD a viable option [5]. BM MSCs secrete paracrine factors, such as growth factors and cytokines, that enhance local angiogenesis and tissue repair [6,7].…”

Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells

“…In clinical transplantation, MSC therapy has been used in tolerance induction or immunosuppression minimization strategies. 17 , 19 , 20 , 33 , 34 , 36 , 61 , 62 In the largest clinical trial to date, 156 patients were enrolled in a single-site, prospective, open-label, randomized study in China. 20 Patients received autologous MSC (1-2 M/kg) at reperfusion and 2 weeks later.…”

“…The immunomodulatory properties of bone marrow-derived mesenchymal stromal cells (MSC) have been recognized for a decade. 13 - 21 Mesenchymal stromal cells suppress T-cell proliferation 13 , 14 , 16 , 17 , 19 , 21 - 25 and dendritic cell differentiation, 13 , 15 - 18 , 25 , 26 and modulate B-cell functions. 13 , 17 , 19 , 22 , 27 - 29 In experimental models, MSC can improve skin, 30 heart, 18 , 21 and kidney transplant outcomes.…”

“… 13 - 21 Mesenchymal stromal cells suppress T-cell proliferation 13 , 14 , 16 , 17 , 19 , 21 - 25 and dendritic cell differentiation, 13 , 15 - 18 , 25 , 26 and modulate B-cell functions. 13 , 17 , 19 , 22 , 27 - 29 In experimental models, MSC can improve skin, 30 heart, 18 , 21 and kidney transplant outcomes. 14 , 16 , 31 , 32 Clinical trials of MSC therapy 17 , 19 , 20 , 33 - 36 indicate that therapy can be used safely if administered prior to transplant and/or combined with adequate immunosuppression to avoid allosensitization.…”

“… 13 , 17 , 19 , 22 , 27 - 29 In experimental models, MSC can improve skin, 30 heart, 18 , 21 and kidney transplant outcomes. 14 , 16 , 31 , 32 Clinical trials of MSC therapy 17 , 19 , 20 , 33 - 36 indicate that therapy can be used safely if administered prior to transplant and/or combined with adequate immunosuppression to avoid allosensitization. We hypothesized that the immunomodulatory properties of MSC may be considered for desensitization strategies.…”