Abstract
BackgroundHuman Placenta-Derived Adherent Cells (PDAC®) are a novel mesenchymal-like cell population derived from normal human placental tissue. PDA-001 is a clinical formulation of PDAC® developed for intravenous administration. In this study, we investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo) in young adult (2–3 month old) and older rats (10–12 months old).MethodsTo evaluate efficacy and determine the optimal number of transplanted cells, young adult Wistar rats were subjected to MCAo and treated 1 day post MCAo with 1×106, 4×106 or 8×106 PDA-001 cells (i.v.), vehicle or cell control. 4×106 or 8×106 PDA-001 cells were also tested in older rats after MCAo. Treatment response was evaluated using a battery of functional outcome tests, consisting of adhesive-removal test, modified Neurological Severity Score (mNSS) and foot-fault test. Young adult rats were sacrificed 56 days after MCAo, older rats were sacrificed 29 days after MCAo, and lesion volumes were measured using H&E. Immunohistochemical stainings for bromodeoxyuridine (BrdU) and von Willebrand Factor (vWF), and synaptophysin were performed.ResultsIn young adult rats, treatment with 4×106 PDA-001 cells significantly improved functional outcome after stroke (p<0.05). In older rats, significant functional improvement was observed with PDA-001 cell therapy in both of the 4×106 and 8×106 treatment groups. Functional benefits in young adult and older rats were associated with significant increases in the number of BrdU immunoreactive endothelial cells, vascular density and perimeter in the ischemic brain, as well as significantly increased synaptophysin expression in the ischemic border zone (p<0.05).ConclusionPDA-001 treatment significantly improved functional outcome after stroke in both young adult and older rats. The neurorestorative effects induced by PDA-001 treatment may be related to increased vascular density and synaptic plasticity.
Highlights
Cell-based therapies currently being evaluated for stroke treatment include neural stem and progenitor cells, cord blood, and bone marrow-derived mesenchymal stromal cells (MSCs) [1,2,3,4]
Bone marrow-derived MSCs (BMSCs) must be obtained through an invasive procedure, are rare in the adult human bone marrow [11], and their number significantly decreases with the age of the individual [12]
Placenta-derived adherent stromal cells have multi-lineage differentiation potential similar to BMSCs in terms of morphology, cell-surface antigen expression, and gene expression patterns, are able to differentiate into many types of cells, are easy to isolate, and large amounts of MSCs can be obtained in culture [8,9,10]
Summary
Cell-based therapies currently being evaluated for stroke treatment include neural stem and progenitor cells, cord blood, and bone marrow-derived mesenchymal stromal cells (MSCs) [1,2,3,4]. Placenta-derived adherent stromal cells have multi-lineage differentiation potential similar to BMSCs in terms of morphology, cell-surface antigen expression, and gene expression patterns, are able to differentiate into many types of cells, are easy to isolate, and large amounts of MSCs can be obtained in culture [8,9,10]. Placenta-Derived Adherent Cells (PDACH) are mesenchymal stromal-like cells isolated from human placental tissue and cultureexpanded [13,14,15]. Like MSCs derived from bone marrow and other sources, PDACH demonstrate immunomodulatory properties in vitro and in animal models. Human Placenta-Derived Adherent Cells (PDACH) are a novel mesenchymal-like cell population derived from normal human placental tissue. We investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo) in young adult (2–3 month old) and older rats (10–12 months old)
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