Bone Marrow Stromal Cells Elicit Tissue Sparing after Acute but Not Delayed Transplantation into the Contused Adult Rat Thoracic Spinal Cord

Abstract

Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue sparing and BMSC survival up to 4 weeks post-transplantation. BMSC survival within the contusion at 7 days post-transplantation was significantly higher with an acute injection (32%) and 3-day delayed injection (52%) than with a 7- or 21-day delayed injection (9% both; p < 0.01). BMSC survival at 28 days post-transplantation was close to 0 in all paradigms, indicating rejection. In contused rats without a BMSC transplant (controls), the volume of spared tissue gradually decreased until 46% (p < 0.001) of the volume of a comparable uninjured spinal cord segment at 49 days post-injury. In rats with BMSC, injected at 15 min, 3, or 7 days post-injury, spared tissue volume was significantly higher in grafted rats than in control rats at the respective endpoints (i.e., 28, 31, and 35 days post-injury). Acute and 3-day delayed but not 7- and 21-day delayed injection of BMSC significantly improved tissue sparing, which was strongly correlated (r = 0.79-1.0) to BMSC survival in the first week after injection into the contusion. Our data showed that neuroprotective effects of BMSC transplanted into a moderate rat spinal cord contusion depend strongly on their survival during the first week post-injection. Acutely injected BMSC elicit more tissue sparing than delayed injected BMSC.