Fetal Immunomodulatory Environment Following Cartilage Injury-The Key to CARTILAGE Regeneration?
Int J Mol Sci
; 22(23)2021 Nov 30.
Article
en En
| MEDLINE
| ID: mdl-34884768
ABSTRACT
Fetal cartilage fully regenerates following injury, while in adult mammals cartilage injury leads to osteoarthritis (OA). Thus, in this study, we compared the in vivo injury response of fetal and adult ovine articular cartilage histologically and proteomically to identify key factors of fetal regeneration. In addition, we compared the secretome of fetal ovine mesenchymal stem cells (MSCs) in vitro with injured fetal cartilage to identify potential MSC-derived therapeutic factors. Cartilage injury caused massive cellular changes in the synovial membrane, with macrophages dominating the fetal, and neutrophils the adult, synovial cellular infiltrate. Correspondingly, proteomics revealed differential regulation of pro- and anti-inflammatory mediators and growth-factors between adult and fetal joints. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult compared to fetal cartilage following injury. In contrast, several immunomodulating proteins and growth factors were expressed significantly higher in the fetus than the adult. Comparison of the in vitro MSCs proteome with the in vivo fetal regenerative signature revealed shared upregulation of 17 proteins, suggesting their therapeutic potential. Biomimicry of the fetal paracrine signature to reprogram macrophages and modulate inflammation could be an important future research direction for developing novel therapeutics.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Osteoartritis
/
Regeneración
/
Cartílago Articular
/
Tratamiento Basado en Trasplante de Células y Tejidos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2021
Tipo del documento:
Article
País de afiliación:
Austria