Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2023; 15(4): 268-280
Published online Apr 26, 2023. doi: 10.4252/wjsc.v15.i4.268
Repetitive administration of cultured human CD34+ cells improve adenine-induced kidney injury in mice
Takayasu Ohtake, Shoichi Itaba, Amankeldi A Salybekov, Yin Sheng, Tsutomu Sato, Mitsuru Yanai, Makoto Imagawa, Shigeo Fujii, Hiroki Kumagai, Masamitsu Harata, 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, Kidney Disease and Transplant center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan
Takayasu Ohtake, Amankeldi A Salybekov, Tsutomu Sato, Takayuki Asahara, Shuzo Kobayashi, Regenerative Medicine, Shonan Research Institute of Innovative Medicine, Kamakura 247-8533, Kanagawa, Japan
Shoichi Itaba, Shigeo Fujii, Hiroki Kumagai, Kamakura Techno-science Inc., Kamakura 248-0036, Japan
Yin Sheng, Advanced Medicine Science, Tokai University School of Medicine, Isehara 259-1193, Japan
Mitsuru Yanai, Department of Pathology, Sapporo Tokushukai Hospital, Sapporo 004-0041, Japan
Makoto Imagawa, Department of Pathology, Sapporo Medical Center, Sapporo 004-0041, Japan
Masamitsu Harata, Human Life CORD Japan Inc, Chuo-ku 103-0012, Tokyo, Japan
Takayuki Asahara, Cell Processing and Cell/Genome Analysis Center, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan
Shuzo Kobayashi, Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanazawa, Japan
Author contributions: Ohtake T contributed to principal investigator, conception and design, provision of study material, collection and assembly of data, data analysis, data interpretation, and manuscript writing; Itaba S, Fujii S, and Kumagai H contributed to animal experiment and data analysis; Salybekov AA and Sheng Y contributed to cell culture and cell population analysis; Sato T contributed to cell preparation and cell population analysis; Yanai M and Imagawa M contributed to immunohistochemical analysis; Harata M contributed to cell preparation; Asahara T contributed to advisor of cell culture, conception and design, confirmation of analytical methods and results, data interpretation, advisor for content of manuscript, and final approval of manuscript; Kobayashi S contributed to conception and design, data interpretation, advisor for content of manuscript, and final approval of manuscript.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Administration Committee of Experimental Animals (No. 20-034 and 20-079).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
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: December 13, 2022
Peer-review started: December 13, 2022
First decision: February 11, 2023
Revised: February 24, 2023
Accepted: March 21, 2023
Article in press: March 21, 2023
Published online: April 26, 2023
Processing time: 134 Days and 5.2 Hours
ARTICLE HIGHLIGHTS
Research background

Chronic kidney Disease (CKD) constitutes a serious public health burden worldwide, and there is no established treatment to impede the progression or restore kidney function in human CKD.

Research motivation

To discover and establish a new effective treatment for CKD is urgently needed. Cell-based therapy has a potential as a new effective treatment for progressive CKD.

Research objectives

To evaluate the efficacy of cultured human cord-blood-derived CD34+ cells.

Research methods

Progressive tubulointerstitial injury with kidney dysfunction was made in mice. Human umbilical cord blood (UCB)-derived CD34+ cells were incubated in vasculogenic conditioned medium for 1 wk to increase the number of CD34+ cells and ability to form endothelial progenitor cell (EPC)-colony-forming units. These cultured human CD34+ cells were administered on days 7, 14, and 21 after the start of adenine diet.

Research results

Cell therapy significantly improved the time-course of progressive kidney dysfunction. Pathological injuries including tubular injury and interstitial fibrosis were significantly reduced in the cell therapy group compared with those in the control group. Preserved microvasculature integrity and decreased macrophage infiltration were shown in the cell therapy group.

Research conclusions

Early intervention using human cultured CD34+ cells significantly improved the progression of tubulointerstitial kidney injury.

Research perspectives

In future research, the efficacy of cultured human CD34+ cells for more advanced CKD such as end-stage renal disease (ESRD), cell behavior (homing and staying in injured kidney) after cell administration, differences in extracellular vesicles from pre- and post-incubated UCB-derived CD34+ cells, should be evaluated for further analysis of the efficacy of cell therapy. A future clinical trial of cell therapy for progressive CKD might be expected.