Long-Term Detection of Human Adipose Derived Mesenchymal Stem Cells After Intra-Articular Injection
OBJECTIVE: Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy of several disorders among which osteo-articular diseases. For such clinical applications, intra-articular (IA) injection of MSCs may be favored for higher safety and specific joint targeting. Although safety of intravenous administration of MSCs has been reported in a number of clinical trials, safety and biodistribution of MSCs after IA injection has not been tested. Our objective was to assess the toxicity of clinical grade human adipose-derived stem cells (hASCs) as well as their biodistribution after IA injection in SCID mice.
METHODS: SCID mice received IA or IV administration of 106 hASC. Several tissues were recovered at different time points and processed for histology or real-time PCR. We used a highly sensitive assay for monitoring hASC distribution, based on amplification of human-specific alu sequences.
RESULTS: Absence of toxicity was observed after ASC infusion. Alu PCR assay exhibits a high sensitivity (1 hASC/105 murine cells) with a large linear range (1-5×104 /105 murine cells). Importantly, 15% of the IA injected hASCs were detectable in the joint for the first month and 1.5% of hASCs engrafted on the long-term, at least 6 months. They were observed in the injected joints and tissues referred as the stem cell niches namely, the bone marrow, the adipose tissue or the muscle.
CONCLUSION: These data argue for the feasibility and safety of using IA delivery of hASC for the treatment of rheumatic diseases affecting the joints.
