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Preclinical safety evaluation and tracing of human mesenchymal stromal cell spheroids following intravenous injection into cynomolgus monkeys
Cheung KwanYeung; Yaping Yan; Li Yan; Yanchao Duan; Enqin Li; Borong Huang; Ke Lu; Koukou Li; Muya Zhou; Lei Zhang; Yaojiong Wu; Kathy Qian Luo; Weizhi Ji; Ren-He Xu; Wei Si
2022-07
Source PublicationBiomaterials
ISSN0142-9612
Volume289
Abstract

We have previously demonstrated that mesenchymal stromal/stem cells (MSCs) in spheroids (MSCsp) tolerate ambient and hypoxic conditions for a prolonged time. Local administration of MSCsp, but not dissociated MSCs (MSCdiss), promotes wound healing and relieves multiple sclerosis and osteoarthritis in mice and monkeys. These findings indicate an advantage of MSCsp over MSCdiss in sustaining cell viability and efficacy following transplantation, which, however, does not appear to apply to intravenous (i.v.) injection for the principal concern that MSCsp might cause embolism in small blood vessels of the host, leading to sudden death. Here, we addressed this concern by injecting human MSCsp (∼450 μm) or MSCdiss i.v. into cynomolgus monkeys. Surprisingly, no deaths occurred until sacrifice at day 21 or 60 post injection, and no remarkable physiological changes were found in the animals following the i.v. injection. The big diameters of large blood vessels in monkeys, compared to small animals like mice, may allow sufficient time for MSCsp to dissociate into single cells so they can pass through small vessels without causing embolism. Retention of MSCsp was lower in the lungs but higher in the blood than retention of MSCdiss at 1 h post injection and both disappeared at day 21. In vitro, MSCsp tolerated fluidic shear stress with higher survival than MSCdiss. Thus, i.v. injection of MSCsp into nonhuman primates is feasible, safe, and probably associated with better survival, less lung entrapment and higher efficacy than administration of MSCdiss.

DOI10.1016/j.biomaterials.2022.121759
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaEngineering ; Materials Science
WOS SubjectEngineering, Biomedical ; Materials Science, bioMaterials
WOS IDWOS:000858432900002
Scopus ID2-s2.0-85137155265
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Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorCheung KwanYeung; Ren-He Xu
AffiliationFHS, University of Macau
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Cheung KwanYeung,Yaping Yan,Li Yan,et al. Preclinical safety evaluation and tracing of human mesenchymal stromal cell spheroids following intravenous injection into cynomolgus monkeys[J]. Biomaterials,2022,289.
APA Cheung KwanYeung,Yaping Yan,Li Yan,Yanchao Duan,Enqin Li,Borong Huang,Ke Lu,Koukou Li,Muya Zhou,Lei Zhang,Yaojiong Wu,Kathy Qian Luo,Weizhi Ji,Ren-He Xu,&Wei Si.(2022).Preclinical safety evaluation and tracing of human mesenchymal stromal cell spheroids following intravenous injection into cynomolgus monkeys.Biomaterials,289.
MLA Cheung KwanYeung,et al."Preclinical safety evaluation and tracing of human mesenchymal stromal cell spheroids following intravenous injection into cynomolgus monkeys".Biomaterials 289(2022).
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