Bone marrow stromal cell (BMSC) transplantation has shown promise for repair of the spinal cord. We showed earlier that a BMSC transplant limits the loss of spinal nervous tissue after a contusive injury. Here, we addressed the premise that BMSC-mediated tissue sparing underlies functional recovery in adult rats after a contusion of the thoracic spinal cord. Our results reveal that after 2 months BMSCs had elicited a significant increase in spared tissue volumes and in blood vessel density in the contusion epicenter. A strong functional relationship existed between spared tissue volumes and blood vessel density. BMSC-transplanted rats exhibited significant improvements in motor, sensorimotor, and sensory functions, which were strongly correlated with spared tissue volumes. Retrograde tracing revealed that rats with BMSCs had twice as many descending brainstem neurons with an axon projecting beyond the contused spinal cord segment and these correlated strongly with the improved motor/sensorimotor functions but not sensory functions. Together, our data indicate that tissue sparing greatly contributes to BMSC-mediated functional repair after spinal cord contusion. The preservation/formation of blood vessels and sparing/regeneration of descending brainstem axons may be important mediators of the BMSC-mediated anatomical and functional improvements.Key words: Transplantation; Bone marrow stromal cell (BMSC); Neuroprotection; Locomotion; Gridwalk; Allodynia
INTRODUCTIONobtain, which warrants their promise for clinical application (25,45,65). BMSC transplantation into the contused rat spinal Contusion of the adult rat thoracic spinal cord causes immediate locomotor and sensory impairments of the cord improves overground walking (15)(16)(17)29,30,33,40,50,71,72). However, this particular gain in motor funchindlimbs (37,62). Spontaneous recovery in locomotor ability reaches plateau levels a few weeks after a contution was not observed in several other studies (2,58, 61,69). Little is known about the effects of BMSC transsion (6,11,36,53). Sensory function remains impaired (32,68) with only small improvements months after plants on contusion-induced sensory impairments. Himes and colleagues (29) showed that BMSC transtrauma (8).Transplantation of repair-promoting cells into the plantation into the contused adult rat spinal cord does not affect thermal hyperalgesia. contused spinal cord has been explored as an intervention to restore function over what is spontaneouslyThe mechanisms underlying BMSC-mediated repair of the contused spinal cord remain elusive. Cell replaceobserved (22,28,51,52,56,60,62). Bone marrow stromal cells (BMSCs) are among the candidate cell types for ment is doubtful as grafted BMSCs survive poorly (30,46,67) and their differentiation into neural cells is spinal cord repair (56,67). BMSCs are relatively easy to moot (12,41,42,47). Another possible repair mechanism with Betadine and 70% alcohol, and Lacrilube ointment was applied to the eyes. The lower thoracic (T) spinal is neuroprotection resulting...