Paracrine Potential of the Human Adipose Tissue-Derived Stem Cells to Modulate Balance between Matrix Metalloproteinases and Their Inhibitors in the Osteoarthritic Cartilage In Vitro

Abstract

Adipose tissue represents an abundant source of stem cells. Along with anti-inflammatory effects, ASC secrete various factors that may modulate metabolism of extracellular matrix in osteoarthritic (OA) cartilage, suggesting that the presence of ASC could be advantageous for OA cartilage due to the recovery of homeostasis between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs). To evaluate these effects, cartilage explants (CE) were cocultured with ASC for 3 and 7 days under stimulation with or without IL-1β. The pattern of gene expression in CE was modified by ASC, including the upregulation of COL1A1 and COL3A1 and the downregulation of MMP13 and COL10A1. The production of MMP-1, MMP-3, and MMP-13 by ASC was not significant; moreover, cocultures with ASC reduced MMP-13 production in CE. In conclusion, active production of TIMP-1, TIMP-2, TIMP-3, IL-6, IL-8, and gelatinases MMP-2 and MMP-9 by ASC may be involved in the extracellular matrix remodelling, as indicated by the altered expression of collagens, the downregulated production of MMP-13, and the reduced chondrocyte apoptosis in the cocultured CE. These data suggest that ASC modulated homeostasis of MMPs/TIMPs in degenerated OA cartilage in vitro and might be favourable in case of the intra-articular application of ASC therapy for the treatment of OA.

Osteogenic Differentiation Modulates the Cytokine, Chemokine, and Growth Factor Profile of ASCs and SHED

“…The secretion of paracrine factors has been pointed out as a major way to enhance the healing process in numerous approaches based on ASCs [ 46 , 47 ] and SHED [ 48 , 49 ]. Based on these forms of evidence, the effect elicited by osteoinduction on the biomolecular profile of ASCs and SHED becomes of great interest.…”

The Potential of Menstrual Blood-Derived Mesenchymal Stem Cells for Cartilage Repair and Regeneration: Novel Aspects

“…MSCs are beneficial for OA repair techniques due to their anti-inflammatory and chondroprotective properties. They are known to secrete a broad range of various paracrine factors and bioactive molecules that can modulate metabolism of extracellular matrix in OA cartilage [7]. Cytokines are major factors that regulate cell differentiation capabilities.…”

“…The cartilage is populated exclusively by chondrocytes; however, its regenerative capacities are limited due to a complicated extracellular matrix (ECM) structure and difficulties associated with repopulating the cells within the tissue after trauma and inflammation [5]. Currently, there is no efficient therapeutic approach for cartilage lesions, and cell-based therapies such as multipotent MSCs from different sources seem promising candidates for cartilage tissue engineering and stimulation of cartilage regeneration [6, 7]. Although the majority of therapeutic techniques using MSCs produce poor outcomes with limited success rates, these cells remain a key focus on studies aimed at differentiating them into a robust chondrogenic lineage and establishing novel protocols for clinical studies.…”

Low‐level laser and adipose‐derived stem cells altered remodelling genes expression and improved collagen reorganization during tendon repair

“…No differences were observed in the expression of Tgfb1 among groups, but the higher concentration of IL-10 in the SC group corroborates the Our results do not demonstrate differences in the amount of TNF-α in the different groups, although the literature describes the anti-inflammatory role of LLL 38 and ASCs. 7,30,44 Low-level laser-treated group presented a larger organization of the fibres, followed by the SCL, SC and T groups. Significant differences between groups marked with the same letter (P < 0.05).…”