title: Human mesenchymal precursor cells (Stro-1⁺) from spinal cord injury patients improve functional recovery and tissue sparing in an acute spinal cord injury rat model.
abstract: This study aimed to determine the potential of purified (Stro-1(+)) human mesenchymal precursor cells (hMPCs) to repair the injured spinal cord (SC) after transplantation into T-cell-deficient athymic RNU nude rats following acute moderate contusive spinal cord injury (SCI). hMPCs were isolated from the bone marrow (BM) stroma of SCI patients and transplanted as a suspension graft in medium [with or without immunosuppression using cyclosporin A (CsA)]. Extensive anatomical analysis shows statistically significant improvement in functional recovery, tissue sparing, and cyst reduction. We provide quantitative assessment of supraspinal projections in combination with functional outcomes. hMPC-transplanted animals consistently achieved mean BBB scores of 15 at 8 weeks post injury. Quantitative histological staining revealed that graft-recipient animals possessed more intact spinal tissue and reduced cyst formation than controls. Fluorogold (FG) retrograde tracing revealed sparing/regeneration of supraspinal and local propriospinal axonal pathways, but no statistical differences were observed compared to controls. Immunohistochemical analysis revealed increased serotonergic (5-HT) and sensory (CGRP) axonal growth within and surrounding transplanted donor hMPCs 2 weeks posttransplantation, but no evidence of hMPC transdifferentiation was seen. Although hMPCs initially survive at 2 weeks posttransplantation, their numbers were dramatically reduced and no cells were detected at 8 weeks posttransplantation using retroviral/lentiviral GFP labeling and a human nuclear antigen (HNA) antibody. Additional immunosuppression with CsA did not improve hMPC survival or their ability to promote tissue sparing or functional recovery. We propose Stro-1(+)-selected hMPCs provide (i) a reproducible source for stem cell transplantation for SC therapy and (ii) a positive host microenvironment resulting in the promotion of tissue sparing/repair that subsequently improves behavioral outcomes after SCI. Our results provide a new candidate for consideration as a stem cell therapy for the repair of traumatic CNS injury.
authors.affiliation: Eileen Bond Spinal Cord Research Laboratory, School of Anatomy and Human Biology, University of Western Australia, Perth, Western Australia.
authors.forename: Stuart I
authors.initials: SI
authors.lastname: Hodgetts
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Simmons
authors.forename: Giles W
authors.initials: GW
authors.lastname: Plant
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D011923:Rats, Nude; D020127:Recovery of Function; D011984:Sensory Receptor Cells / Q000502:physiology; D059326:Serotonergic Neurons / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine