Human mesenchymal stromal/stem cells recruit resident pericytes and induce blood vessels maturation to repair experimental spinal cord injury in rats

• Published in: Scientific reports Vol. 10; no. 1; p. 19604
• Main Authors: Menezes, Karla, Rosa, Barbara Gomes, Freitas, Catarina, da Cruz, Aline Silva, de Siqueira Santos, Raphael, Nascimento, Marcos Assis, Alves, Daiana Vieira Lopes, Bonamino, Martin, Rossi, Maria Isabel, Borojevic, Radovan, Coelho-Sampaio, Tatiana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-11-2020; Nature Publishing Group
• Subjects: 631/532/2118/2074; 692/617/375/1824; Adipose tissue; Angiogenesis; Animals; Blood vessels; Blood Vessels - drug effects; Blood Vessels - physiology; Blood-Brain Barrier; Cell culture; Cell Movement; Cell therapy; Compression; Culture media; Culture Media, Conditioned - chemistry; Culture Media, Conditioned - pharmacology; Endothelium, Vascular - cytology; Female; Hemorrhage - blood; Hemorrhage - therapy; Humanities and Social Sciences; Humans; Injections, Spinal; Lesions; Locomotion; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - cytology; Mesenchyme; multidisciplinary; Neovascularization, Physiologic - genetics; Nestin; Nestin - metabolism; Pericytes; Pericytes - cytology; Platelet-derived growth factor; Rats, Sprague-Dawley; Science; Science (multidisciplinary); Spinal cord injuries; Spinal Cord Injuries - pathology; Spinal Cord Injuries - therapy; Stem cell transplantation; Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-76290-0

Angiogenesis is considered to mediate the beneficial effects of mesenchymal cell therapy in spinal cord injury. After a moderate balloon-compression injury in rats, injections of either human adipose tissue-derived stromal/stem cells (hADSCs) or their conditioned culture media (CM-hADSC) elicited angiogenesis around the lesion site. Both therapies increased vascular density, but the presence of hADSCs in the tissue was required for the full maturation of new blood vessels. Only animals that received hADSC significantly improved their open field locomotion, assessed by the BBB score. Animals that received CM-hADSC only, presented haemorrhagic areas and lack pericytes. Proteomic analyses of human angiogenesis-related factors produced by hADSCs showed that both pro- and anti-angiogenic factors were produced by hADSCs in vitro, but only those related to vessel maturation were detectable in vivo. hADSCs produced PDGF-AA only after insertion into the injured spinal cord. hADSCs attracted resident pericytes expressing NG2, α-SMA, PDGF-Rβ and nestin to the lesion, potentially contributing to blood vessel maturation. We conclude that the presence of hADSCs in the injured spinal cord is essential for tissue repair.