Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats

Abstract

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>The results of the present study indicate that an ascorbic acid–induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.</jats:p></jats:sec>

Polypyrrole/polylactic acid nanofibrous scaffold cotransplanted with bone marrow stromal cells promotes the functional recovery of spinal cord injury in rats

“…In our study, implantation of PPy/PLA nanofibrous scaffold resulted in downregulation of the chondroitin sulfate proteoglycan, which is a strong axon regeneration inhibitor molecule in the extracellular matrix in the injured area . Moreover, transplantation of BMSCs has shown to suppress glial scar formation in rat spinal cord injury . In the present study, BMSCs transplantation caused the significant downregulation of this inhibitory molecule.…”

Annulus fibrosus cell sheets limit disc degeneration in a rat annulus fibrosus injury model

“…A promising new technology in which cell sheets are produced has been used for regenerating various organs . Instead of obtaining single or aggregated cells in suspension, cell sheet products are comprised of a layer of monolayer cultured cells .…”

“…12 A promising new technology in which cell sheets are produced has been used for regenerating various organs. [17][18][19][20][21] Instead of obtaining single or aggregated cells in suspension, cell sheet products are comprised of a layer of monolayer cultured cells. 19,22 The cell sheets can be obtained by, for example, culturing specific cell populations on a thermoresponsive polymer, which can thereafter be detached from the culture plate by altering the environmental temperature, giving rise to a dissociated but intact sheet of the cultured cells.…”

Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury

“…BMSCs support axonal regrowth in both acute (18,19) and chronic (20) cord transection. BMSCs are capable of building a niche inside the host from which diverse growth factors and molecules for axonal guidance and extension are secreted, promoting an enabling environment for axonal regrowth (21)(22)(23).…”