Alleviation of osteoarthritis by intra-articular transplantation of circulating mesenchymal stem cells

Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):25-32. doi: 10.1016/j.bbrc.2022.10.064. Epub 2022 Oct 21.

Abstract

This study aimed to evaluate the efficacy of intra-articular delivery of peripheral blood derived mesenchymal stromal cells (PB-MSCs) on the progression of trauma-induced osteoarthritis (OA) in mice. Adult male C57BL/6J mice subjected to destabilization of the medial meniscus surgeries (DMM) were randomly divided into four groups: sham surgery group; vehicle control group (treated with saline), PBMSC-treated group, or adipose tissue derived MSCs (AD-MSC)-treated group (n = 4 per group). PB-MSCs and AD-MSCs were harvested and cultured following previously established protocols, and pre-labeled with BrdU for 48 h before transplantation. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3-5) were intra-articular injected into the right knee joints thrice post-surgery. The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations. PB-MSCs administration significantly reduced subchondral bone volume comparing to the vehicle control group. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which was comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of the PB-MSCs treated group comparing to that of the vehicle control group. Co-expression of BrdU and Sox9 indicated that injected PB-MSCs differentiated in chondrocytes in situ, along with reduced levels of IL-6 within peripheral sera of PB-MSCs- and AD-MSCs-treated mice. Therefore, administration of PB-MSCs or AD-MSCs attenuated trauma-induced OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs are ideal cell source for treating cartilage-associated diseases.

Keywords: Cartilage; Chondrogenesis; Chronic inflammation; Mesenchymal stromal cells; Osteoarthritis; Peripheral blood.

Publication types

  • Randomized Controlled Trial, Veterinary
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine
  • Cartilage, Articular* / metabolism
  • Disease Models, Animal
  • Injections, Intra-Articular
  • Male
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Osteoarthritis* / pathology

Substances

  • Bromodeoxyuridine