Optimal Preclinical Conditions for Using Adult Human Multipotent Neural Cells in the Treatment of Spinal Cord Injury.

Autor: Won JS; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea., Yeon JY; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea.; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea., Pyeon HJ; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea., Noh YJ; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea., Hwang JY; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea., Kim CK; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea.; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Korea., Nam H; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea.; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea., Lee KH; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Korea., Lee SH; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea.; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea., Joo KM; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea.; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea.; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.; Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea.; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Korea.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Mar 04; Vol. 22 (5). Date of Electronic Publication: 2021 Mar 04.
DOI: 10.3390/ijms22052579
Abstrakt: Stem cell-based therapeutics are amongst the most promising next-generation therapeutic approaches for the treatment of spinal cord injury (SCI), as they may promote the repair or regeneration of damaged spinal cord tissues. However, preclinical optimization should be performed before clinical application to guarantee safety and therapeutic effect. Here, we investigated the optimal injection route and dose for adult human multipotent neural cells (ahMNCs) from patients with hemorrhagic stroke using an SCI animal model. ahMNCs demonstrate several characteristics associated with neural stem cells (NSCs), including the expression of NSC-specific markers, self-renewal, and multi neural cell lineage differentiation potential. When ahMNCs were transplanted into the lateral ventricle of the SCI animal model, they specifically migrated within 24 h of injection to the damaged spinal cord, where they survived for at least 5 weeks after injection. Although ahMNC transplantation promoted significant locomotor recovery, the injection dose was shown to influence treatment outcomes, with a 1 × 10 6 (medium) dose of ahMNCs producing significantly better functional recovery than a 3 × 10 5 (low) dose. There was no significant gain in effect with the 3 × 10 6 ahMNCs dose. Histological analysis suggested that ahMNCs exert their effects by modulating glial scar formation, neuroprotection, and/or angiogenesis. These data indicate that ahMNCs from patients with hemorrhagic stroke could be used to develop stem cell therapies for SCI and that the indirect injection route could be clinically relevant. Moreover, the optimal transplantation dose of ahMNCs defined in this preclinical study might be helpful in calculating its optimal injection dose for patients with SCI in the future.
Databáze: MEDLINE