Implantation of Autologous Selected Renal Cells in Diabetic Chronic Kidney Disease Stages 3 and 4—Clinical Experience of a “First in Human” Study

Abstract

IntroductionAnimal models of chronic kidney disease demonstrate that a redundant population of therapeutically bioactive selected renal cells (SRCs) can be delivered to the kidney through intraparenchymal injection and arrest disease progression. Direct injection of SRCs has been shown to attenuate nuclear factor−κB, which is known to drive tissue inflammation, as well as the transforming growth factor−β−mediated plasminogen activator inhibitor−1 response that drives tissue fibrosis.MethodsWe present experience from the first-in-human clinical study with SRCs. Seven male type 2 diabetic patients (63 ± 2 years of age) with chronic kidney disease stage 3 to 4 (estimated glomerular filtration rate 25 ± 2 ml/min) were recruited. After blood and urine sampling, iohexol clearance, magnetic resonance imaging, and renal scintigraphy, patients underwent ultrasound-guided renal biopsy. Two cores of renal tissue were shipped to the manufacturing plant for cell isolation, culture, and product preparation. Formulated SRCs were transported back to study sites (range 59–87 days after biopsy) for intracortical injection using a retroperitoneoscopic technique.ResultsLaparoscopically assisted implantation of SRCs was uneventful in all patients. However, postoperative complications were common and suggest that other techniques of SRC delivery should be used. Kidney volume, split function, and glomerular filtration rate did not change during 12 months of follow-up. An extended 24-month follow-up in 5 of the patients showed a decline in estimated glomerular filtration rate (cystatin C).DiscussionPostoperative complications following retroperitoneoscopic implantation of SRC in the kidney cortex seem to be related to the surgical procedure rather than to injection of the cell product. No changes in renal function were observed during the original 12-month protocol. Beyond the first 12 months after cell implantation, individual renal function began to deteriorate during further follow-up.

Renal volumetry with magnetic resonance imaging

“…This transplantation had been carried out within the framework of a larger study on the potentially beneficial effects of autologous stem cell transplantation in kidneys in patients with type 2 diabetic chronic kidney disease stage III-IV, where renal volume change was one of the outcomes. The overall outcome of the autologous transplantation study has been published elsewhere ( 7 ). A total of 200 kidney image stacks were thus processed.…”

Cell-derived Secretome for the Treatment of Renal Disease

“…While most of the secretome studies have focused on MSC as a source of secretome, several studies have reported that different types of therapeutic cells could be used as secretome sources. As noted above, primary renal cells demonstrated therapeutic effects on the improvement of renal functions 4,5,52) . Dominguez et al showed the therapeutic effects of primary renal cell-derived secretome on kidney improvement 53) .…”

“…A commonly used approach in cell-based therapy is cell transplantation, where therapeutic cells are exogenously administered to achieve the repair. The cell transplantation approach using various cell types have resulted in reno-therapeutic outcomes in many pre-clinical [1][2][3] and clinical studies 4) . For example, primary renal cells isolated from kidney tissues were introduced to improve renal functions from kidney diseases in a pre-clinical 5) and clinical study 4) .…”

“…The cell transplantation approach using various cell types have resulted in reno-therapeutic outcomes in many pre-clinical [1][2][3] and clinical studies 4) . For example, primary renal cells isolated from kidney tissues were introduced to improve renal functions from kidney diseases in a pre-clinical 5) and clinical study 4) . Similarly, various stem cells, including adult, fetal, embryonic, and induced pluripotent stem cells also have been extensively studied as therapeutic cell sources and demonstrated the beneficial therapeutic effects in renal failure 6) .…”

Protocol and Baseline Data on Renal Autologous Cell Therapy Injection in Adults with Chronic Kidney Disease Secondary to Congenital Anomalies of the Kidney and Urinary Tract

“…This current trial uses a percutaneous, image-guided techniques with conscious sedation. The phase I trial of high-risk CKD diabetics who were injected with RE-ACT used a laparoscopically assisted surgical approach and general anesthesia [18]. Furthermore, the cellbased therapeutic could be administered (mean eGFR <30 mL/min) safely in a small cohort [17].…”