Intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis

Abstract

BackgroundRheumatoid arthritis (RA) is a debilitating and painful disease leading to increased morbidity and mortality and novel therapeutic approaches are needed. The purpose of this study was to elucidate if mesenchymal stem cells (MSCs) injected in the joints of mice with arthritis are therapeutic, reducing joint swelling and cartilage destruction.MethodsMurine mesenchymal stem cells (mMSCs) were isolated from bone marrow of C57Bl/6 mice and expanded in culture. Cells were tested for immunophenotype and their ability to form colonies and to differentiate into chondrocytes, osteocytes and adipocytes. Antigen-induced arthritis (AIA) was induced by intra-articular injection of methylated bovine serum albumin into the knee joints of preimmunized C57Bl/6 mice. After one day, when peak swelling occurs, 500,000 mMSCs labelled with red fluorescent cell tracker CM-DiI were injected intra-articularly in the right knee joint. Left knee joints were treated as controls by receiving PBS injections. Differences between groups were calculated by Mann Whitney U test or unpaired t tests using GraphPad Prism software version 5.ResultsKnee joint diameter (swelling) was measured as a clinical indication of joint inflammation and this parameter was significantly less in MSC-treated mice compared to control-treated animals 48 hours after arthritis induction. This difference continued for ~7 days. CM-DiI-labelled MSCs were clearly visualised in the lining and sublining layers of synovium, in the region of the patella and femoral and tibial surfaces. By day 3, parameters indicative of disease severity, including cartilage depletion, inflammatory exudate and arthritic index were shown to be significantly reduced in MSC-treated animals. This difference continued for 7 days and was further confirmed by histological analysis. The serum concentration of tumour necrosis factor α was significantly decreased following MSC administration.ConclusionsOur results reveal that MSCs injected in the joints of mice with AIA are therapeutic, reducing inflammation, joint swelling and cartilage destruction. These cells also integrate into the synovium in AIA.

Canine adipose tissue-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating T cells in rats

“…Previous studies have shown that injected MSCs can migrate to injured lungs, livers, kidneys, and colons [1115182934]. In the present study, the use of CM-DiI facilitated tracking of injected MSCs [2338]. A large number of systemically administered CM-DiI-labeled cAT-MSCs were detected in the injured pancreas, which was confirmed by PCR amplification of cRPS5, the canine-specific reference gene [5].…”

The effect of intra‐articular injection of autologous bone marrow stem cells on pain and knee function in patients with osteoarthritis

“…3 To our knowledge this is the first clinical controlled trial with autologous BM-SC stimulated in vivo with a single intra-articular injection for the treatment of knee OA. Our study differs from other research developed in [24][25][26][27][28][29] In humans, other studies have been performed using stem cells from different collection sites such as adipose tissue [30][31][32][33] or peripheral blood through apheresis. 34,35 Some studies include case series and clinical trials with BM mesenchymal cells; some of them administered the cells by means of surgical intervention 13,[36][37][38] and others with intra-articular injection.…”

Intra-Articular Injection of Human Synovial Membrane-Derived Mesenchymal Stem Cells in Murine Collagen-Induced Arthritis: Assessment of Immunomodulatory Capacity In Vivo

“…Previous studies have shown that MSCs injected intra-articularly are retained at the injection site for 1–4 weeks, without migration to distant organs such as the lungs, spleen, and liver [30, 31]. …”