The role of placental-derived adherent stromal cell (PLX-PAD) in the treatment of critical limb ischemia.

Background Aims: Mesenchymal stromal cells (MSC) are spindle-shaped plastic-adherent cells isolated from bone marrow (BM), adipose tissue and other organs, including the placenta. Autologous BM-derived MSC have been studied in animals with experimentally induced critical limb ischemia (CLI) as a model of end-stage peripheral vascular disease. While demonstrating therapeutic benefit, the use of these cells is limited by the need to surgically extract BM and the fear of thrombosis secondary to the use of granulocyte-colony-stimulating factor (G-CSF) to mobilize the cells.

Safety and biodistribution profile of placental-derived mesenchymal stromal cells (PLX-PAD) following intramuscular delivery.

The administration of mesenchymal stromal cells (MSCs) provides an exciting emerging therapeutic modality for the treatment of peripheral arterial disease, a condition that is associated with critical limb ischemia as its end stage. Placental-derived MSCs, termed PLX-PAD cells, are stable adhesive stromal cells isolated from full-term human placentae, cultured on carriers, and expanded in a bioreactor called the PluriX. These cells can be expanded in vitro without phenotypic or karyotypic changes.

Spontaneous aortitis in the Balb/c mouse.

We examined whether high incidence rates (18%-56%) of inflammation in the root of the aorta detected in a Balb/c mouse model for hind limb ischemia were related to the surgical procedure. Twenty mice underwent ligation of the femoral artery; incidences of aortic root inflammation were compared to those observed in controls. We used a multiple-section sampling method to increase the sensitivity of the diagnostic rates.

CXCL12 (SDF-1alpha) suppresses ongoing experimental autoimmune encephalomyelitis by selecting antigen-specific regulatory T cells.

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the central nervous system induced by antigen-specific effector Th17 and Th1 cells. We show that a key chemokine, CXCL12 (stromal cell-derived factor 1alpha), redirects the polarization of effector Th1 cells into CD4(+)CD25(-)Foxp3(-)interleukin (IL) 10(high) antigen-specific regulatory T cells in a CXCR4-dependent manner, and by doing so acts as a regulatory mediator restraining the autoimmune inflammatory process. In an attempt to explore the therapeutic implication of these findings, we have generated a CXCL12-immunoglobulin (Ig) fusion protein that, when administered during ongoing EAE, rapidly suppresses the disease in wild-type but not IL-10-deficient mice.

Placental-derived and expanded mesenchymal stromal cells (PLX-I) to enhance the engraftment of hematopoietic stem cells derived from umbilical cord blood.

For the past 40 years, bone marrow transplantation (BMT) has become standard therapy to re-establish marrow function in patients with damaged or defective bone marrow. A human leukocyte antigen-matched sibling is the donor of choice for patients needing transplantation of allogeneic hematopoietic stem cells (HSCs). As most patients do not have an acceptable matched, related donor, the National Marrow Donor Program has been established to match volunteer bone marrow donors with potential recipients who require BMT.

Targeted overexpression of IL-18 binding protein at the central nervous system overrides flexibility in functional polarization of antigen-specific Th2 cells.

The current study shows that functional polarization of Ag-specific CD4(+) Th2 cells entering the CNS during the accelerating phase of experimental autoimmune encephalomyelitis is flexible and dependent on the cytokine milieu there. Thus, targeted cell/gene therapy by Ag-specific T cells overexpressing IL-18 binding protein overrides this flexibility and induces infectious spread of T cell tolerance. Using a congenic system, we demonstrated that at this time, Ag-specific Th2 cells accumulate at the CNS but then arrest of IL-4 production.