Mesenchymal Stem Cells Derived from Peripheral Blood Protects against Ischemia

Abstract

Intravenous delivery of mesenchymal stem cells (MSCs) prepared from bone marrow (BMSCs) reduces infarction volume and ameliorates functional deficits in a rat cerebral ischemia model. MSClike multipotent precursor cells (PMSCs) have also been suggested to exist in peripheral blood. To test the hypothesis that treatment with PMSCs may have a therapeutic benefit in stroke, we compared the efficacy of systemic delivery of BMSCs and PMSCs. A permanent middle cerebral artery occlusion (MCAO) in rat was induced by intraluminal vascular occlusion with a microfilament. Rat BMSCs and PMSCs were prepared in culture and intravenously injected into the rats 6 h after MCAO. Lesion size was assessed at 6 h, and 1, 3, and 7 days using MR imaging and histology. The hemodynamic change of cerebral blood perfusion on stroke was assessed the same times using perfusion-weighted image (PWI). Functional outcome was assessed using the treadmill stress test. Both BMSCs and PMSCs treated groups had reduced lesion volume, improved regional cerebral blood flow, and functional improvement compared to the control group. The therapeutic benefits of both MSC-treated groups were similar. These data suggest that PMSCs derived from peripheral blood could be an important cell source of cell therapy for stroke.

Therapeutic Benefits by Human Mesenchymal Stem Cells (hMSCs) and Ang-1 Gene-Modified hMSCs after Cerebral Ischemia

“…Perfusion-weighted imaging was acquired using T 2 *-weighted (TR = 13 ms, TE = 6.0 ms) gradient echo sequence (Ukai et al, 2007). A dynamic image series of 30 measurements resulted in a total scan time of 26 secs, with a fields of view of 30 mm and image acquisition matrix of 128 Â 64, which was interpolated by zero-filling to 512 Â 512.…”

Pulmonary Passage is a Major Obstacle for Intravenous Stem Cell Delivery: The Pulmonary First-Pass Effect

“…Therefore, if stem cell therapy is to be broadly applied as a therapeutic strategy, a simple intravenous (IV) approach would be ideal, given broad biodistribution and easy access. Consequently, intravenous infusion has been used as the route of cell delivery for a large number of preclinical studies [4][5][6] and is the route of delivery for some early clinical trials [7,8]. However, questions have been raised regarding the ability to obtain a critical number of cells to the area of injury with a systemic intravenous approach [9][10][11].…”

Human Stem/Progenitor Cells from Bone Marrow Enhance Glial Differentiation of Rat Neural Stem Cells: A Role for Transforming Growth Factor β and Notch Signaling

“…The nonhematopoietic population of adult stem=progeni-tor cells from bone marrow referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) were shown to produce therapeutic effects in numerous animal models of neurodegenerative diseases, including cerebral ischemia, Parkinson's disease, multiple sclerosis, spinal cord injury, and traumatic brain injury [5][6][7][8][9][10]. Given their ability to home to multiple tissues, including the CNS, MSCs may be a viable means to stimulate the endogenous NSC population to assume a neuroprotective or neuroregenerative role.…”