title: Customized platelet-rich plasma with transforming growth factor β1 neutralization antibody to reduce fibrosis in skeletal muscle.
abstract: The formation of fibrous tissue during the healing of skeletal muscle injuries leads to incomplete recovery of the injured muscle. Platelet-rich-plasma (PRP) contains beneficial growth factors for skeletal muscle repair; however, it also contains deleterious cytokines and growth factors, such as TGF-β1, that can cause fibrosis and inhibit optimal muscle healing.
  
  
  OBJECTIVE
  To test if neutralizing TGF-β1's action within PRP, through neutralization antibodies, could improve PRP's beneficial effect on skeletal muscle repair.
  
  
  METHODS
  PRP was isolated from in-bred Fisher rats. TGF-β1 neutralization antibody (Ab) was used to block the TGF-β1 within the PRP prior to injection. The effects of customized PRP (TGF-β1 neutralized PRP) on muscle healing was tested on a cardiotoxin (CTX) induced muscle injury model.
  
  
  RESULTS
  A significant increase in the numbers of regenerative myofibers was observed in the PRP and customized PRP groups compared to the untreated control. A significant decrease in collagen deposition was observed in customized PRP groups when compared to the control and PRP groups. Significantly enhanced angiogenesis and more Pax-7 positive satellite cells were found in the PRP and customized PRP groups compared to the control group. Macrophage infiltration was increased in the customized PRP groups when compared with the PRP group. More M2 macrophages were recruited to the injury site in the customized PRP groups when compared with the PRP and control groups.
  
  
  CONCLUSIONS
  Neutralizing TGF-β1 within PRP significantly promotes muscle regeneration while significantly reducing fibrosis. Not only did the neutralization reduce fibrosis, it enhanced angiogenesis, prolonged satellite cell activation, and recruited a greater number of M2 macrophages to the injury site which also contributed to the efficacy that the customized PRP had on muscle healing.
authors.affiliation: Musculoskeletal Growth & Regeneration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: hongshuai.li@pitt.edu.
authors.forename: Hongshuai
authors.initials: H
authors.lastname: Li
authors.affiliation: Musculoskeletal Growth & Regeneration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: juhicks@wakehealth.edu.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Hicks
authors.affiliation: Vascular Medicine Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: lingwang@pitt.edu.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Musculoskeletal Growth & Regeneration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: nickmoyster@gmail.com.
authors.forename: Nick
authors.initials: N
authors.lastname: Oyster
authors.affiliation: Steadman Philippon Research Institute, Vail, CO 81657, USA. Electronic address: drphilippon@sprivail.org.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Philippon
authors.affiliation: Department of Orthopaedic Surgery, University of North Carolina in Chapel Hill, Chapel Hill, NC 27514, USA. Electronic address: shurwitz@abos.org.
authors.forename: Shepard
authors.initials: S
authors.lastname: Hurwitz
authors.affiliation: Musculoskeletal Growth & Regeneration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: hoganmv@upmc.edu.
authors.forename: MaCalus V
authors.initials: MV
authors.lastname: Hogan
authors.affiliation: Steadman Philippon Research Institute, Vail, CO 81657, USA; Department of Orthopaedic Surgery, University of Texas Health Science Center at Houston, TX 77054, USA. Electronic address: johnny.huard@uth.tmc.edu.
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D005355:Fibrosis; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology / Q000293:injuries* / Q000473:pathology*; D009135:Muscular Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D053657:Platelet-Rich Plasma / Q000276:immunology; D011916:Rats, Inbred F344; D012038:Regeneration; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D053773:Transforming Growth Factor beta1
keywords: Fibrosis; Muscle injury; Neutralization; Platelet-rich plasma; TGF-Beta 1