Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Preliminary evidence of renal function improvement in chronic progressive kidney disease using autologous CD34+ cell therapy: A clinical trial
Takayasu Ohtake, Tsutomu Sato, Toshitaka Tsukiyama, Suguru Muraoka, Ayaka Mitomo, Haruka Maruyama, Mizuki Yamano, Yasuhiro Mochida, Kunihiro Ishioka, Machiko Oka, Hidekazu Moriya, Sumi Hidaka, Haruchika Masuda, Takayuki Asahara, Shuzo Kobayashi
Takayasu Ohtake, Regenerative Medicine, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan
Takayasu Ohtake, Suguru Muraoka, Ayaka Mitomo, Haruka Maruyama, Mizuki Yamano, Yasuhiro Mochida, Kunihiro Ishioka, Machiko Oka, Hidekazu Moriya, Sumi Hidaka, Shuzo Kobayashi, Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan
Takayasu Ohtake, Haruchika Masuda, Takayuki Asahara, Shuzo Kobayashi, Regenerative Medicine, Shonan Research Institute of Innovative Medicine, Kamakura 247-8533, Kanagawa, Japan
Tsutomu Sato, Clinical Laboratory, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan
Toshitaka Tsukiyama, Department of Radiology and Interventional Radiology, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
Author contributions: Ohtake T contributed as principal investigator and doctor in charge; Ohtake T and Kobayashi S designed the research study; Sato T contributed to cell preparation and cell population analysis; Tsukiyama T contributed to cell administration into renal arteries as director of IVR center; Muraoka S, Mitomo A, Maruyama H, Yamano M, Mochida Y, Ishioka K, Oka M, Moriya H, and Hidaka S contributed to clinical support as attending physicians; Mochida Y contributed statistical analyses; Masuda H and Asahara T gave comments for safety profile and advised for content of the manuscript; Ohtake T wrote the manuscript. All authors have read and approved the final manuscript.
Institutional review board statement: The study protocol conformed to the Declaration of Helsinki and was approved by the Special Committee for Class II Regenerative Medicine and certified by the Ministry of Health, Labor, and Welfare in Japan (SKRM-2-020).
Clinical trial registration statement: This study was registered at the official clinical trial registration site (jRCTb030210237).
Informed consent statement: Written informed consent was obtained from all patients.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data can be supplied for reasonable requests.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Takayasu Ohtake, MD, PhD, Director, Doctor, Regenerative Medicine, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura 247-8533, Kanagawa, Japan.
ohtake@shonankamakura.or.jp
Received: May 5, 2024
Revised: October 8, 2024
Accepted: November 12, 2024
Published online: December 26, 2024
Processing time: 221 Days and 18 Hours
BACKGROUND
To date, no specific treatment has been established to reverse progressive chronic kidney disease (CKD).
AIM
To evaluate the safety and efficacy of autologous CD34+ cell transplantation in CKD patients who exhibited a progressive decline in renal function.
METHODS
The estimated glomerular filtration rate (eGFR) at the beginning of the study was 15.0-28.0 mL/minute/1.73 m2. After five days of treatment with the granulocyte colony-stimulating factor, mononuclear cells were harvested and CD34+ cells were magnetically collected. CD34+ cells were directly injected into the bilateral renal arteries twice (at 0 and 3 months), and their safety and efficacy were evaluated for 6 months.
RESULTS
Four patients were enrolled and completed the study. Three of four patients showed improvement in eGFR slope (eGFR slope > 0 mL/minute/1.73 m2), with the monthly slope of eGFR (delta eGFR) changing from -1.36 ± 1.1 (pretreatment) to +0.22 ± 0.71 (at 6 months) mL/minute/1.73 m2/month (P = 0.135) after cell therapy. Additionally, intrarenal resistive index (P = 0.004) and shear wave velocity (P = 0.04) were significantly improved after cell therapy. One patient experienced transient fever after cell therapy, and experienced bone pain during granulocyte colony-stimulating factor administration. However, no severe adverse events were reported.
CONCLUSION
In conclusion, our findings suggest that repetitive peripheral blood-derived autologous CD34+ cell transplantation into the renal arteries is safe, feasible, and may be effective for patients with progressive CKD. However, a large-scale clinical trial is warranted to validate the efficacy of repetitive regenerative cell therapy using autologous CD34+ cells in patients with progressive CKD.
Core Tip: Chronic kidney disease (CKD) progresses to end-stage renal disease, and it is often very difficult to retard its progression. Therefore, new and effective therapies for CKD are urgently needed. We administered granulocyte colony-stimulating factor-mobilized autologous CD34 positive cells directly into renal arteries. The progressive decline in the estimated glomerular filtration rate improved after 1st cell therapy in three of four patients and was almost preserved after 2nd cell therapy. Although this was an exploratory small clinical trial, the results provide new insights in the field of regenerative medicine for progressive CKD.
