Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats—similarities to astrocyte grafts

Abstract

Neurotransplantation has been used to explore the development of the central nervous system and for repair of diseased tissue in conditions such as Parkinson's disease. Here, we examine the effects of direct injection into rat brain of human marrow stromal cells (MSCs), a subset of cells from bone marrow that include stem-like precursors for nonhematopoietic tissues. Human MSCs isolated by their adherence to plastic were infused into the corpus striatum. Five to 72 days later, brain sections were examined for the presence of the donor cells. About 20% of the infused cells had engrafted. There was no evidence of an inflammatory response or rejection. The cells had migrated from the injection site along known pathways for migration of neural stem cells to successive layers of the brain. After infusion into the brain, the human MSCs lost their immunoreactivity to antibodies for collagen I. Initially, the human cells continued to stain with antibodies to fibronectin but the region of staining with fibronectin was significantly decreased at 30 and 72 days. The results suggest that MSCs may be useful vehicles for autotransplantation in both cell and gene therapy for a variety of diseases of the central nervous system.

Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis

“…rMSCs were isolated from the femurs of adult rats as previously described (Azizi et al, 1998) and maintained in Dulbecco's modified Eagle's medium (DMEM; Life Technologies, Bethesd, MD) supplemented with 20% Fetal Bovine Serum (FBS, Atlanta Biologicals, Atlanta, GA). Early-passage MSCs were subjected to flow cytometry to determine purity as described by Woodbury et al (2000).…”

Engineering mesenchymal stem cells for immunotherapy

“…Following intracerebral implantation, MSCs were able to proliferate, differentiate and appeared to migrate along the well-defined neural migration pathways. 21,22 Moreover, intracerebral injection of marrow MSCs in a mouse model of types A and B Niemann-Pick disease (NPD) revealed that transplanted cells survived at least 6 months after transplant and significantly delayed the Purkinje cell loss characteristic of NPD. 23 In another study, patients with osteogenesis imperfecta (a genetic disorder caused by a mutation in the type I collagen gene and characterized by generalized osteopenia) have been treated by systemic injection of allogeneic bone marrow.…”

Remyelination of the spinal cord following intravenous delivery of bone marrow cells

“…Bone marrow stromal cells can differentiate into astrocytes when transplanted into rodent brain (Azizi et al, 1998;Kopen et al, 1999), into neurons in vitro under appropriate cell culture conditions (Woodbury et al, 2000), and myocytes when injected into the heart following acute infarction (Orlic et al, 2001a). Systemic injection of bone marrow cells into lethally Xirradiated mice leads to differentiation of neuronal cells in brain (Brazelton et al, 2000;Mezey et al, 2000).…”