Human mesenchymal stromal/stem cells recruit resident pericytes and induce blood vessels maturation to repair experimental spinal cord injury in rats
- PMID: 33177535
- PMCID: PMC7658254
- DOI: 10.1038/s41598-020-76290-0
Human mesenchymal stromal/stem cells recruit resident pericytes and induce blood vessels maturation to repair experimental spinal cord injury in rats
Abstract
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.
Conflict of interest statement
All authors declare no potential competing interest, financial or non-financial interests in relation to the work described. KM is a faculty at Petropolis Medical School and declares no potential conflict of interest. ASC declares no potential conflict of interest. MAN declares no potential conflict of interest. RSS, DVLA, CF declare no potential conflict of interest. MB is part of the Molecular Carcinogenesis Program—Coordination of Research—National Cancer Institute (INCA), and is Vice President of Research and Biological Collections (VPPCB), Oswaldo Cruz Institute Foundation (FIOCRUZ) and declares no potential conflict of interest. MIR declares no potential conflict of interest. RB is a scientific consultant at the Petropolis Medical School and president of the Rio de Janeiro Cell Bank and of APABCAM—Scientific Technical Association Paul Ehrlich, and declares no potential conflict of interest. TCS declares no potential conflict of interest.
Figures










References
-
- Beggs JL, Waggener JD. Microvascular regeneration following spinal cord injury: the growth sequence and permeability properties of new vessels. Adv. Neurol. 1979;22:191–206. - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources