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Recovery of Function Following Grafting of Human Bone Marrow-Derived Stromal Cells into the Injured Spinal Cord

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, Department of Veterans Affairs Hospital, Philadelphia, PA

Birgit Neuhuber, PhD

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA

Carl Coleman

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA

Robert Kushner

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA

Sharon A. Swanger

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA

Gene C. Kopen, PhD

Neuronyx Inc., Malvern, PA

Joseph Wagner, PhD

Neuronyx Inc., Malvern, PA

Jed S. Shumsky, PhD

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA

Itzhak Fischer, PhD

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, itzhak.fischer{at}drexelmed.edu

This study evaluates functional recovery after transplanting human bone marrow-derived stromal cells (BMSCs) into contusion models of spinal cord injury (SCI). The authors used a high-throughput process to expand BMSCs and characterized them by flow cytometry, ELISA, and gene expression. They found that BMSCs secrete neurotrophic factors and cytokines with therapeutic potential for cell survival and axon growth. In adult immune-suppressed rats, mild, moderate, or severe contusions were generated using the MASCIS impactor. One week following injury, 0.5 to 1 x 106 BMSCs were injected into the lesioned spinal cord; control animals received vehicle injection. Biweekly behavioral tests included the Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB), exploratory rearing, grid walking, and thermal sensitivity. Animals receiving moderate contusions followed by BMSC grafts showed significant behavioral recovery in BBB and rearing tests when compared to controls. Animals receiving BMSC grafts after mild or severe contusion showed trends toward improved recovery. Immunocytochemistry identified numerous axons passing through the injury in animals with BMSC grafts but few in controls. BMSCS were detected at 2 weeks after transplantation; however, at 11 weeks very few grafted cells remained. The authors conclude that BMSCs show potential for repairing SCI. However, the use of carefully characterized BMSCs improved transplantation protocols ensuring BMSC, survival, and systematic motor and sensory behavioral testing to identify robust recovery is imperative for further improvement.

Key Words: Bone marrow stromal cells • Contusion injury • Functional recovery • Regeneration • Spinal cord injury • Xenografts

Neurorehabilitation and Neural Repair, Vol. 20, No. 2, 278-296 (2006)
DOI: 10.1177/1545968306286976


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