title: Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model.
abstract: This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN-LEW) (n = 4) hindlimb transplants were performed and assessed for neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic nerve cut-and-repair and treated with either local or systemic injection of MSCs had significant improvement in the speed of recovery of compound muscle action potential amplitudes and axon counts when compared with negative controls. Similarly, rats undergoing allogeneic hindlimb transplants treated with local injection of MSCs exhibited significantly increased axon counts. Similarly, systemic MSC treatment resulted in improved nerve regeneration following allogeneic hindlimb transplants. Systemic administration had a more pronounced effect on electromotor recovery while local injection was more effective at increasing fiber counts, suggesting different targets of action. Local and systemic MSC injections significantly improve the pace and degree of nerve regeneration after nerve injury and hindlimb transplantation.
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Damon S
authors: DS
authors: Cooney
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Eric G
authors: EG
authors: Wimmers
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Zuhaib
authors: Z
authors: Ibrahim
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Johanna
authors: J
authors: Grahammer
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Joani M
authors: JM
authors: Christensen
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Gabriel A
authors: GA
authors: Brat
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Lehao W
authors: LW
authors: Wu
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Karim A
authors: KA
authors: Sarhane
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Joseph
authors: J
authors: Lopez
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Christoph
authors: C
authors: Wallner
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Georg J
authors: GJ
authors: Furtmüller
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Nance
authors: N
authors: Yuan
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: John
authors: J
authors: Pang
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Kakali
authors: K
authors: Sarkar
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: W P Andrew
authors: WP
authors: Lee
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Gerald
authors: G
authors: Brandacher
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D006614:Hindlimb / Q000637:transplantation*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009416:Nerve Regeneration; D010524:Peripheral Nervous System Neoplasms / Q000628:therapy*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000293:injuries*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014945:Wound Healing