title: Bone marrow-derived mesenchymal stem cells obtained during arthroscopic rotator cuff repair surgery show potential for tendon cell differentiation after treatment with insulin.
abstract: OBJECTIVE
  The purpose of this study was to determine whether a one-time physiologic dose of insulin when compared with the growth factors insulin-like growth factor 1, β-fibroblastic growth factor, and growth differentiation factor 5 is capable of differentiating bone marrow-derived mesenchymal stem cells (MSCs) into tendon.
  
  
  METHODS
  Eleven patients undergoing arthroscopic rotator cuff repair consented to undergo aspiration of bone marrow. A dose-response curve was calculated to determine the optimal dose of insulin needed to differentiate MSCs into tendon. After purification of bone marrow in the operating room, MSCs were exposed to either insulin or tendon-inducing growth factors or were left untreated to serve as a control. The potential for MSCs in each of these groups to differentiate into tendon was evaluated with a multistep process that included determination of the genetic upregulation for tendon-specific proteins, confirmation that the levels of these proteins were actually increased, staining of the MSCs with antibodies for these proteins to ensure that they were expressed on the cell surface, and finally, evaluation of cell morphology to verify the MSCs' tendon-like appearance.
  
  
  RESULTS
  MSCs treated with insulin showed increased gene expression of tendon-specific markers (P < .05), increased content of tendon-specific proteins (P < .05), and increased receptors on the cell surface (P < .05) compared with control cells. Histologic analysis showed a tendon-like appearance compared with the control cells.
  
  
  CONCLUSIONS
  Bone marrow-derived MSCs treated with a single physiologic dose of insulin differentiated into cells with characteristics consistent with tendon.
  
  
  CONCLUSIONS
  The potential for MSCs to differentiate into tendon after a 1-time dose of insulin may assist in developing practical biologic options for augmentation of rotator cuff repairs.
authors: Department of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut 06034, USA. mazzocca@uchc.edu
authors: Augustus D
authors: AD
authors: Mazzocca
authors: Mary Beth R
authors: MB
authors: McCarthy
authors: David
authors: D
authors: Chowaniec
authors: Mark P
authors: MP
authors: Cote
authors: Christopher H
authors: CH
authors: Judson
authors: John
authors: J
authors: Apostolakos
authors: Olga
authors: O
authors: Solovyova
authors: Knut
authors: K
authors: Beitzel
authors: Robert A
authors: RA
authors: Arciero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001182:Arthroscopy; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D058575:Decorin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000494:pharmacology; D055428:Growth Differentiation Factor 5 / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017006:Rotator Cuff / Q000601:surgery*; D000070636:Rotator Cuff Injuries; D019063:Tenascin / Q000378:metabolism; D013710:Tendons / Q000166:cytology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024042:Collagen Type I; D024061:Collagen Type III; D058575:Decorin; D005346:Fibroblast Growth Factors; D055428:Growth Differentiation Factor 5; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D047908:Intracellular Signaling Peptides and Proteins; D019063:Tenascin; C525893:GDF5 protein, human; C093504:SCX protein, human