title: The effect of a polyurethane-based reverse thermal gel on bone marrow stromal cell transplant survival and spinal cord repair.
abstract: Cell therapy for nervous tissue repair is limited by low transplant survival. We investigated the effects of a polyurethane-based reverse thermal gel, poly(ethylene glycol)-poly(serinol hexamethylene urethane) (ESHU) on bone marrow stromal cell (BMSC) transplant survival and repair using a rat model of spinal cord contusion. Transplantation of BMSCs in ESHU at three days post-contusion resulted in a 3.5-fold increase in BMSC survival at one week post-injury and a 66% increase in spared nervous tissue volume at four weeks post-injury. These improvements were accompanied by enhanced hindlimb motor and sensorimotor recovery. In vitro, we found that ESHU protected BMSCs from hydrogen peroxide-mediated death, resulting in a four-fold increase in BMSC survival with two-fold fewer BMSCs expressing the apoptosis marker, caspase 3 and the DNA oxidation marker, 8-oxo-deoxyguanosine. We argue that ESHU protected BMSCs transplanted is a spinal cord contusion from death thereby augmenting their effects on neuroprotection leading to improved behavioral restoration. The data show that the repair effects of intraneural BMSC transplants depend on the degree of their survival and may have a widespread impact on cell-based regenerative medicine.
authors: Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Gaby J
authors: GJ
authors: Ritfeld
authors: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Britta M
authors: BM
authors: Rauck
authors: Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Tabitha L
authors: TL
authors: Novosat
authors: Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Colorado Denver, Aurora, CO, USA.
authors: Daewon
authors: D
authors: Park
authors: Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Pavan
authors: P
authors: Patel
authors: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Raymund A C
authors: RA
authors: Roos
authors: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA; The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: yaw20@pitt.edu.
authors: Yadong
authors: Y
authors: Wang
authors: Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: moudega@pitt.edu.
authors: Martin
authors: M
authors: Oudega
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D005260:Female; D005782:Gels / Q000494:pharmacology; D007150:Immunohistochemistry; D011140:Polyurethanes / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000628:therapy*; D058630:Spinal Cord Regeneration / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D005782:Gels; D011140:Polyurethanes
keywords: Antioxidant; Cell therapy; ESHU; Neuroprotection; Repair; Spinal cord injury