title: Long-term detection of human adipose-derived mesenchymal stem cells after intraarticular injection in SCID mice.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy for several disorders, among them the osteoarticular diseases. For such clinical applications, intraarticular (IA) injection of MSCs may be favored for higher levels of safety and targeting of specific joints. Although the safety of intravenous (IV) administration of MSCs has been reported in a number of clinical trials, the safety and biodistribution of MSCs after IA injection have not been tested. Our objective was to assess the toxicity of clinical-grade human adipose-derived MSCs (AD-MSCs), as well as their biodistribution, after IA injection into SCID mice.
  
  
  METHODS
  SCID mice received IA or IV administration of 10(6) human AD-MSCs. Several tissues were recovered at different time points and processed for histologic assessment or real-time polymerase chain reaction (PCR) analysis. A highly sensitive assay was used to monitor the distribution of AD-MSCs, based on amplification of human-specific Alu sequences.
  
  
  RESULTS
  Absence of toxicity was observed after AD-MSC infusion. Alu PCR assay revealed a high sensitivity (1 human AD-MSC/10(5) murine cells), with a large linear range (1-5 × 10(4) /10(5) murine cells). Importantly, 15% of the IA-injected AD-MSCs were detectable in the joint for the first month and 1.5% of the AD-MSCs engrafted over the long term, at least 6 months. AD-MSCs were observed in the injected joints and in areas of tissue referred to as stem cell niches, such as the bone marrow, adipose tissue, and muscle.
  
  
  CONCLUSIONS
  These data support the feasibility and safety of using IA delivery of human AD-MSCs in the treatment of rheumatic diseases that affect the joints.
authors.affiliation: INSERM U844, Hôpital St. Eloi, and Université Montpellier 1, Montpellier, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Toupet
authors.forename: Marie
authors.initials: M
authors.lastname: Maumus
authors.forename: Julie-Anne
authors.initials: JA
authors.lastname: Peyrafitte
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourin
authors.forename: Peter L E M
authors.initials: PL
authors.lastname: van Lent
authors.forename: Rosanna
authors.initials: R
authors.lastname: Ferreira
authors.forename: Béatrice
authors.initials: B
authors.lastname: Orsetti
authors.forename: Nelly
authors.initials: N
authors.lastname: Pirot
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Danièle
authors.initials: D
authors.lastname: Noël
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007270:Injections, Intra-Articular; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID