Transplantation of Human Marrow Stromal Cells and Mono-Nuclear Bone Marrow Cells Into the Injured Spinal Cord

Abstract

Two groups of 6 rats received dorsolateral funiculotomies followed by direct injection of bone marrow stromal cells (MSC) or mono-nuclear fraction of bone marrow (mnBM). Animals were killed at 4 or 21 days. Cellular transplantation is a promising treatment strategy for spinal cord injury (SCI); however, most cells need to be cultured before transplantation introducing burdensome steps for clinical application. Cells immediately available for transplantation, like mnBM, would be preferable. Previous studies have shown that MSC transplants promote protection and repair after SCI. MSC are attractive for transplantation because of easy isolation and availability of autologous sources. MSC are derived from whole bone marrow, purified and expanded in culture for a period of at least 2 weeks. Alternatively, mnBM could be used for transplantation. mnBM derived from bone marrow from through simple centrifugation can be reimplantated within hours; however, the presence of immune cells may be problematic. Cultured MSC or mnBM from human donors were acutely transplanted into SCI. After sacrifice, spinal cord sections were histologically analyzed for presence of graft-derived immune cells, host immune response, tissue sparing, glial scar formation, and grafting efficacy. mnBM did not give rise to mature immune cells after transplantation into SCI, or evoke an increased host immune response or tissue loss compared to MSC-transplanted animals. In contrast, host macrophage/microglia response was increased early after MSC transplantation, perhaps due to exposure of cells to serum-containing media. The glial scar was less prominent after mnBM transplantation at day 4. At 21 days, differences had subsided and MSC and mnBM macrophage responses and effects on glial scarring were comparable. MSC and mnBM engraftment efficiencies were also similar. The use of mnBM is a viable alternative to MSC for transplantation into SCI and may dramatically ease clinical translation.