Functional recovery of chronic paraplegic pigs after autologous transplantation of bone marrow stromal cells.

BACKGROUND: Bone marrow stromal cells (BMSC) transplantation offers promise in the treatment of chronic paraplegia in rodents. Here, we report the effect of this cell therapy in adult pigs suffering chronic paraplegia. METHODS: Three months after spinal cord injury, autologous BMSC in autologous plasma was injected into lesion zone and adjacent subarachnoid space in seven paraplegic pigs. On the contrary, three paraplegic pigs only received autologous plasma. Functional outcome was measured weekly until the end of the follow-up, 3 months later. RESULTS: Our present study showed progressive functional recovery in transplanted pigs. At this time, intramedullary posttraumatic cavities were filled by a neoformed tissue containing several axons, together with BMSC that expressed neuronal or glial markers. Furthermore, in the treated animals, electrophysiological studies showed recovery of the previously abolished somatosensory-evoked potentials. CONCLUSIONS: These findings confirm previous observations in rodents and support the possible utility of BMSC transplantation in humans suffering chronic paraplegia.

Neurotrophic Schwann-cell factors induce neural differentiation of bone marrow stromal cells.

Neural transdifferentiation of bone marrow stromal cells has been questioned, because cell fusion could explain the development of new cell types, misinterpreted as transdifferentiated cells. We performed here cocultures of bone marrow stromal cells and Schwann cells, without possibility that both cell types can establish contact. In these conditions, bone marrow stromal cells expressed nestin 4 h after beginning cocultures, and strong expression of neuronal markers was disclosed at 72 h, increasing at 1 and 2 weeks. Our results support that neural transdifferentiation of bone marrow stromal cells is induced by soluble factors provided by glial cells, and suggest that cell fusion should not be significant when local bone marrow stromal cells administration for neural repair is considered.

Cell therapy using bone marrow stromal cells in chronic paraplegic rats: systemic or local administration?

Recent studies showed the therapeutic effect of bone marrow stromal cells (BMSC) after spinal cord injury (SCI). In the present study, we compared the effect of systemic and local administration of BMSC in adult Wistar rats suffering chronic paraplegia as consequence of severe SCI. Adult Wistar rats were subjected to a weight-drop impact causing complete paraplegia, and 3 months later, all the animals remained without signs of functional recovery. At this moment, 3 x 10(6) BMSC were injected intravenously (n: 20) or into traumatic spinal cord cavity (n: 20). Outcome was evaluated until sacrifice of the animals, 6 months later, using the Basso-Beattie-Bresnehan (BBB) score, the cold spray test, and measuring the thigh perimeter. After sacrifice, samples of spinal cord tissue were studied histologically. The results showed that intravenous administration of BMSC achieves some degree of functional recovery when compared to controls. Nevertheless, administration of BMSC into postraumatic spinal cord cavity promotes a clear and progressive functional recovery, significantly superior to the recovery obtained by means of the intravenous administration. This effect is associated to long-term presence of BMSC in the injured spinal cord tissue, with images suggesting neuronal differentiation and spinal cord reconstruction.

Schwann cells induce neuronal differentiation of bone marrow stromal cells.

Bone marrow stromal cells are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. Recently, bone marrow stromal cells have been shown to have the capacity to differentiate into neurons under specific experimental conditions, using chemical factors. We now describe how bone marrow stromal cells can be induced to differentiate into neuron-like cells when they are co-cultured with Schwann cells. When compared with chemical differentiation, expression of neuronal differentiation markers begins later, but one week after beginning co-culture, most bone marrow stromal cells showed a typical neuronal morphology. Our present findings support the transdifferentiation of bone marrow stromal cells, and the potential utility of these cells for the treatment of degenerative and acquired disorders of the nervous system.

Effects of dexamethasone on apoptosis-related cell death after spinal cord injury.

OBJECT: The purpose of this study was to analyze the expression of F7-26 (Apostain) in injured spinal cord tissue, and the modifying effects of dexamethasone administration. METHODS: A total of 56 adult female Wistar rats were subjected to traumatic spinal cord injury (SCI) to induce complete paraplegia. These rats were divided into two groups according to whether they received dexamethasone (doses of 1 mg/kg daily) post-SCI. Injured spinal cord tissue was studied by means of conventional histological techniques, and Apostain expression was determined by immunohistochemical analysis at 1, 4, 8, 24, and 72 hours, and at 1 and 2 weeks after SCI in all the animals. Apostain-positive cells, mainly neurons and glial cells, were detected 1 hour after injury, peaking at 8 hours, after which the number decreased. One week after injury, apoptosis was limited to a few glial cells, mainly oligodendrocytes, and 2 weeks after injury there was no evidence of Apostain-positive cells. In the group of paraplegic rats receiving post-SCI intraperitoneal dexamethasone, there was a significant decrease in the number of Apostain-positive cells. CONCLUSIONS: Analysis of the results indicated that apoptosis plays a role in the early period after SCI and that administration of dexamethasone decreases apoptosis-related cell death in the injured spinal cord tissue.