title: Acute mobilization and migration of bone marrow-derived stem cells following anterior cruciate ligament rupture.
abstract: Little is known regarding acute local and systemic processes following anterior cruciate ligament (ACL) rupture. No study has elucidated whether bone marrow-derived mesenchymal stem cells (MSCs) are mobilized into circulation and recruited to the injured joint.
  
  
  
  In Part 1, Lewis rats were randomized to noninvasive ACL rupture (Rupture) or non-injured (Control) (n = 6/group). After 72 h, whole blood MSC concentration was assessed using flow cytometry. Synovial fluid and serum were assayed for stromal cell-derived factor (SDF)-1α and cartilage degeneration biomarkers, respectively. In Part 2, 12 additional rats were randomized and intravenously-injected with fluorescently-labeled allogenic MSCs. Cell tracking was performed using longitudinal, in vivo and ex vivo near-infrared (NIR) imaging and histology. Synovium SDF-1α and interleukin (IL)-17A immunostaining was performed. Serum was assayed for SDF-1α and 29 other cytokines.
  
  
  
  In Part 1, there was a significant increase in MSC concentration and synovial fluid SDF-1α in Rupture. No differences in cartilage biomarkers were observed. In Part 2, Rupture had significantly higher NIR signal at 24, 48, and 72 h, indicating active recruitment of MSCs to the injured joint. Ex vivo cell tracking demonstrated MSC localization in the synovium and myotendinous junction (MTJ) of the quadriceps. Injured synovia exhibited increased synovitis grade and higher degree of IL-17A and SDF-1α immunostaining.
  
  
  
  ACL rupture induced peripheral blood mobilization of MSCs and migration of intravenously-injected allogenic MSCs to the injured joint, where they localized in the synovium and quadriceps MTJ.
authors.affiliation: Orthopaedic Research Laboratory, Beaumont Health, Royal Oak, MI, USA; Department of Orthopaedic Surgery, Oakland University - William Beaumont School of Medicine, Rochester, MI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Maerz
authors.affiliation: Orthopaedic Research Laboratory, Beaumont Health, Royal Oak, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Fleischer
authors.affiliation: Orthopaedic Research Laboratory, Beaumont Health, Royal Oak, MI, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Newton
authors.affiliation: Orthopaedic Research Laboratory, Beaumont Health, Royal Oak, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Davidson
authors.affiliation: Orthopaedic Research Laboratory, Beaumont Health, Royal Oak, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Salisbury
authors.affiliation: Department of Orthopaedic Surgery, Beaumont Health, Royal Oak, MI, USA.
authors.forename: P
authors.initials: P
authors.lastname: Altman
authors.affiliation: Orthopaedic Research Laboratory, Beaumont Health, Royal Oak, MI, USA; Department of Orthopaedic Surgery, Oakland University - William Beaumont School of Medicine, Rochester, MI, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Kurdziel
authors.affiliation: Department of Orthopaedic Surgery, Oakland University - William Beaumont School of Medicine, Rochester, MI, USA; Department of Orthopaedic Surgery, Beaumont Health, Royal Oak, MI, USA.
authors.forename: K
authors.initials: K
authors.lastname: Anderson
authors.affiliation: MedSport and Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bedi
authors.affiliation: Orthopaedic Research Laboratory, Beaumont Health, Royal Oak, MI, USA; Department of Orthopaedic Surgery, Oakland University - William Beaumont School of Medicine, Rochester, MI, USA. Electronic address: kevin.baker@beaumont.edu.
authors.forename: K C
authors.initials: KC
authors.lastname: Baker
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries / Q000473:pathology / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011897:Random Allocation; D011917:Rats, Inbred Lew; D012421:Rupture / Q000503:physiopathology; D013582:Synovial Fluid / Q000166:cytology
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12
keywords: Anterior cruciate ligament rupture; Cellular recruitment; Mesenchymal stem cells; Migration; Mobilization; Post-traumatic osteoarthritis