Intracranial transplantation of monocyte‐derived multipotential cells enhances recovery after ischemic stroke in rats

Abstract

Cell transplantation has emerged as a potential therapy to reduce the neurological deficits caused by ischemic stroke. We previously reported a primitive cell population, monocyte-derived multipotential cells (MOMCs), which can differentiate into mesenchymal, neuronal, and endothelial lineages. In this study, MOMCs and macrophages were prepared from rat peripheral blood and transplanted intracranially into the ischemic core of syngeneic rats that had undergone a left middle cerebral artery occlusion procedure. Neurological deficits, as evaluated by the corner test, were less severe in the MOMC-transplanted rats than in macrophage-transplanted or mock-treated rats. Histological evaluations revealed that the number of microvessels that had formed in the ischemic boundary area by 4 weeks after transplantation was significantly greater in the MOMC-transplanted rats than in the control groups. The blood vessel formation was preceded by the appearance of round CD31(+) cells, which we confirmed were derived from the transplanted MOMCs. Small numbers of bloodvessels incorporating MOMC-derived endothelial cells expressing a mature endothelial marker RECA-1 were detected at 4 weeks after transplantation. In addition, MOMCs expressed a series of angiogenic factors, including vascular endothelial growth factor, angiopoetin-1, and placenta growth factor (PlGF). These findings provide evidence that the intracranial delivery of MOMCs enhances functional recovery by promoting neovascularization in a rat model for ischemic stroke.

Platelet-Derived Stromal Cell-Derived Factor-1 Is Required for the Transformation of Circulating Monocytes into Multipotential Cells

“…This population originates from circulating CD14 + monocytes, and contains primitive cells that can differentiate into cells with the typical phenotypes and functions of mesenchymal cells, neurons, and endothelium in vitro [8]–[12]. We recently showed that the intracranial delivery of MOMCs enhances functional recovery in a rat model for ischemic stroke [13]. On the other hand, MOMCs derived from patients with systemic sclerosis were functionally altered and deficient in their ability to differentiate into endothelial cells, either in vitro or in vivo [14].…”

A new biomarker candidate for spinal muscular atrophy: Identification of a peripheral blood cell population capable of monitoring the level of survival motor neuron protein

“…In recent years, several cultured human-cell populations originating from circulating monocytes have been reported. Those cultured monocytes have the capacity to differentiate into non-phagocytic pluripotent stem cell-like phenotypes and are named “pluripotent stem cells (PSCs)” [ 44 ], “monocyte-derived multipotential cells (MOMCs)” [ 45 – 47 ], or “programmable cells of monocytic origin (PCMOs)” [ 48 , 49 ]. As proof of pluripotency, cultured monocytes are reported to differentiate into epithelial-, endothelial-, hepatocytic-, pancreatic islet-, and neuronal-phenotype cells.…”

Stem Cell Therapy for Ischemic Stroke: From Bench to Bedside

“…14 of the included studies delivered stem cells at 1 week or later after MCAo. 13 of these studies, including some in which stem cells were only administered 4 weeks after MCAo, reported an improvement in behavioral and/or histologic outcome [45,49,55,63,68,[70][71][72][73][74][75][76][77][78]. The other study did not report significant improvement in histologic outcome and even worsening of behavior was noted [62].…”