Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis

Abstract

IntroductionMesenchymal stem cells (MSCs) can differentiate into various connective tissue cells. Several techniques have been used for the clinical application of MSCs in articular cartilage repair; however, there are many issues associated with the selection of the scaffold material, including its ability to support cell viability and differentiation and its retention and degradation in situ. The application of MSCs via a scaffold also requires a technically demanding surgical procedure. The aim of this study was to test the outcome of intra-articular transplantation of mesenchymal stem cells suspended in hyaluronic acid (HA) in the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis (OA).MethodsCommercially available human MSCs were cultured, labeled with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE), suspended in either PBS or HA, and injected into the knee joints of 7-month-old animals. The control animals were injected with either PBS or HA alone. The animals were sacrificed at 1, 3, and 5 weeks post transplantation, the knee joints harvested, and fluorescent microscopic analysis was performed. Histological and immunohistochemical analysis were performed at 5 weeks post transplantation.ResultsAt 5 weeks post transplantation, partial cartilage repair was noted in the HA-MSC group but not in the other groups. Examination of CFDA-SE-labeled cells demonstrated migration, differentiation, and proliferation of MSC in the HA-MSC group. There was strong immunostaining for type II collagen around both residual chondrocytes and transplanted MSCs in the OA cartilage.ConclusionThis scaffold-free and technically undemanding technique appears to result in the regeneration of articular cartilage in the spontaneous OA animal model. Although further examination of the long-term effects of transplantation is necessary, the findings suggest that intra-articular injection of HA-MSC mixture is potentially beneficial for OA.

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.…”

Preliminary Clinical Results With Lipoaspirate Stromal Vascular Cell Fraction in Treatment of Patients With Knee Osteoarthritis

“…Доклинические исследования на животных показали безопасность и эффективность кле-ток СВФ в лечении ДОА, хрящевых дефектов или других ортопедических заболеваний [3,23,29]. Немногочисленные пилотные исследования продемонстрировали хорошую переносимость, безопасность, а также клиническую эффектив-ность СВФ у пациентов с ранними стадиями ДОА [6,13,16,25].…”

Treatment of osteoarthritis with mesenchymal stem cells

“…Further investigations have demonstrated that BM-MSCs from Trpv4 −/− mice showed decreased adipogenesis and osteogenesis phenotypes, whereas A-MSCs from Trpv4 −/− mice exhibited increased adipogenesis and osteogenesis and decreased chondrogenesis compared with those in wild type controls, indicating that Trpv4 plays a chondroprotective role during OA progression [96]. Recent investigations found that in OA animal models, intra-articular injection of MSCs decreased articular cartilage erosion, probably by inhibiting MMP-13, TNF-α, and IL-1β expression [75,97]. Because MMP-13, TNF-α, and IL-1β expressions were associated with Wnt/β-catenin, MAPK, and BMP signaling based on the studies mentioned above, we inferred that these signals may also be involved in the effects of MSC treatment on OA (Figure 1).…”

“…Twelve weeks after five million allogeneic Luc/LacZ + synovium-MSCs were injected, LacZ-positive regenerated menisci producing type II collagen were found, and the LacZ gene derived from MSCs was not found in any other organs except in synovium. In a spontaneous OA model in guinea pigs, seven million human commercial MSCs (Lonza, Basel, Switzerland) with hyaluronic acid (HA) were injected into the OA joint [75]. Five weeks after transplantation, partial cartilage regeneration with type II collagen expression was Treatment reduced matrix degrading enzymes and TNF-α in the cartilage matrix and inhibited MMP-1 and TNF-α expression in the synovial membrane and menisci.…”