Preclinical assessments of safety and tumorigenicity of very high doses of allogeneic human umbilical cord mesenchymal stem cells.

Autor: Chin SP; Cytopeutics Sdn Bhd, Bio-X Centre, Persiaran Cyberpoint Selatan, Suite 2-3, 2nd Floor, Cyber 8, 63000, Cyberjaya, Selangor, Malaysia. chin.sze.piaw@gmail.com.; CMH Specialist Hospital, Jalan Tun Dr. Ismail, 70200, Seremban, Negeri Sembilan, Malaysia. chin.sze.piaw@gmail.com.; M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman (UTAR), Bandar Sungai Long, 43000, Kajang, Selangor, Malaysia. chin.sze.piaw@gmail.com., Saffery NS; Cytopeutics Sdn Bhd, Bio-X Centre, Persiaran Cyberpoint Selatan, Suite 2-3, 2nd Floor, Cyber 8, 63000, Cyberjaya, Selangor, Malaysia., Then KY; Cytopeutics Sdn Bhd, Bio-X Centre, Persiaran Cyberpoint Selatan, Suite 2-3, 2nd Floor, Cyber 8, 63000, Cyberjaya, Selangor, Malaysia.; Cryocord Sdn Bhd, Cyber 8, 63000, Cyberjaya, Selangor, Malaysia., Cheong SK; M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman (UTAR), Bandar Sungai Long, 43000, Kajang, Selangor, Malaysia.
Jazyk: angličtina
Zdroj: In vitro cellular & developmental biology. Animal [In Vitro Cell Dev Biol Anim] 2024 Mar; Vol. 60 (3), pp. 307-319. Date of Electronic Publication: 2024 Feb 29.
DOI: 10.1007/s11626-024-00852-z
Abstrakt: Human umbilical cord-mesenchymal stem cells (hUC-MSCs) have been widely investigated as a new therapeutic agent to treat injuries and inflammatory-mediated and autoimmune diseases. Previous studies have reported on the safety of low-dose infusion of hUC-MSCs, but information on the cell behaviour at higher doses and frequency of injection of the cells remains uncertain. The aim of the present study was to demonstrate the safety and efficacy of hUC-MSCs by Cytopeutics® (Selangor, Malaysia) from low to an extremely high dose in different monitoring periods in healthy BALB/c mice as well as assessing the tumorigenicity of the cells in B-NDG SCID immunocompromised mice. Umbilical cord from two healthy human newborns was obtained and the isolation of the hUC-MSCs was performed based on previous established method. Assessment of the cells at different doses of single or multiple administrations was performed on healthy BALB/c mice in dose range finding, sub-acute (7 d and 28 d) and sub-chronic periods (90 d). Tumorigenicity potential of Cytopeutics® hUC-MSCs was also evaluated on B-NDG immunocompromised mice for 26 wk. Single or multiple administrations of Cytopeutics® hUC-MSCs up to 40 × 10 6 cells per kilogramme of body weight (kg BW) were found to have no adverse effect in terms of clinical symptoms, haematology and other laboratory parameters, and histology examination in healthy BALB/c mice. hUC-MSCs were also found to reduce pro-inflammatory cytokines (IL-6 and TNF-α) in a dose-dependent manner. No sign of tumor formation was observed in B-NDG mice in the 26-wk tumorigenicity assessment. Single or multiple administration of allogenic Cytopeutics® hUC-MSCs was safe even at very high doses, is non-tumorigenic and did not cause adverse effects in mice throughout the evaluation periods. In addition, Cytopeutics® hUC-MSCs exhibited immunomodulatory effect in a dose-dependent manner.
(© 2024. The Author(s).)
Databáze: MEDLINE
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