Cell transplantation
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Cell transplantation · Jan 2013
Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice.
Stem cell transplantation therapy has emerged as a potential treatment for ischemic stroke and other neurodegenerative diseases. Effective delivery of exogenous cells and homing of these cells to the lesion region, however, have been challenging issues that hinder the efficacy and efficiency of cell-based therapy. In the present investigation, we tested a delayed treatment of noninvasive and brain-targeted intranasal delivery of bone marrow mesenchymal stem cells (BMSCs) in a mouse focal cerebral ischemia model. ⋯ Three days after transplantation and 4 days after stroke, both N-BMSCs and HP-BMSCs decreased cell death in the peri-infarct region; significant neuroprotection of reduced infarct volume was seen in mice that received HP-BMSCs. In adhesive removal test of sensorimotor functional assay performed 3 days after transplantation, HP-BMSC-treated mice performed significantly better than N-BMSC- and vehicle-treated animals. These data suggest that delayed intranasal administration of stem cells is feasible in the treatment of stroke and hypoxic preconditioning of transplanted cells, significantly enhances cell's homing to the ischemic region, and optimizes the therapeutic efficacy.
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Cell transplantation · Jan 2013
Human mesenchymal precursor cells (Stro-1⁺) from spinal cord injury patients improve functional recovery and tissue sparing in an acute spinal cord injury rat model.
This study aimed to determine the potential of purified (Stro-1(+)) human mesenchymal precursor cells (hMPCs) to repair the injured spinal cord (SC) after transplantation into T-cell-deficient athymic RNU nude rats following acute moderate contusive spinal cord injury (SCI). hMPCs were isolated from the bone marrow (BM) stroma of SCI patients and transplanted as a suspension graft in medium [with or without immunosuppression using cyclosporin A (CsA)]. Extensive anatomical analysis shows statistically significant improvement in functional recovery, tissue sparing, and cyst reduction. We provide quantitative assessment of supraspinal projections in combination with functional outcomes. hMPC-transplanted animals consistently achieved mean BBB scores of 15 at 8 weeks post injury. ⋯ Additional immunosuppression with CsA did not improve hMPC survival or their ability to promote tissue sparing or functional recovery. We propose Stro-1(+)-selected hMPCs provide (i) a reproducible source for stem cell transplantation for SC therapy and (ii) a positive host microenvironment resulting in the promotion of tissue sparing/repair that subsequently improves behavioral outcomes after SCI. Our results provide a new candidate for consideration as a stem cell therapy for the repair of traumatic CNS injury.
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Cell transplantation · Jan 2013
ABCG2 protects kidney side population cells from hypoxia/reoxygenation injury through activation of the MEK/ERK pathway.
Breast cancer resistance protein 1 (BCRP1/ABCG2) is used to identify the side population (SP) within a population of cells, which is enriched for stem and progenitor cells in different tissues. Here, we investigated the role of extracellular signal-regulated kinase (ERK) 1/2 in the signaling mechanisms underlying ischemic/hypoxic conditions in kidney SP cells. Kidney SP cells were isolated using Hoechst 33342 dye-mediated fluorescein-activated cell sorting and then incubated under hypoxia/reoxygenation (H/R) with or without verapamil, a selective BCRP1/ABCG2 inhibitor. ⋯ When administered systemically into animals with renal ischemia/reperfusion injury, the SP cells significantly improved renal function, accelerated mitogenic response, and reduced cell apoptosis. However, this improved therapeutic potential of SP cells was significantly reduced by pretreatment with verapamil. Collectively, these findings provide evidence for a crucial role for the MEK/ERK-ABCG2 pathway in protecting kidney SP cells from ischemic/hypoxic injury.
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Cell transplantation · Jan 2013
Electroacupuncture promotes the differentiation of transplanted bone marrow mesenchymal stem cells overexpressing TrkC into neuron-like cells in transected spinal cord of rats.
Our previous study indicated that electroacupuncture (EA) could increase neurotrophin-3 (NT-3) levels in the injured spinal cord, stimulate the differentiation of transplanted bone marrow mesenchymal stem cells (MSCs), and improve functional recovery in the injured spinal cord of rats. However, the number of neuron-like cells derived from the MSCs is limited. It is known that NT-3 promotes the survival and differentiation of neurons by preferentially binding to its receptor TrkC. ⋯ In addition, the conduction of cortical motor-evoked potentials (MEPs) and hindlimb locomotor function increased as compared to controls (treated with the LacZ-MSCs, TrkC-MSCs, and LacZ-MSCs + EA groups). In the TrkC-MSCs + EA group, the injured spinal cord also showed upregulated expression of the proneurogenic factors laminin and GAP-43 and downregulated GFAP and chondroitin sulfate proteoglycans (CSPGs), major inhibitors of axonal growth. Together, our data suggest that TrkC-MSC transplantation combined with EA treatment spinal cord injury not only increased MSC survival and differentiation into neuron-like cells but also promoted CST regeneration across injured sites to the caudal cord and functional improvement, perhaps due to increase of NT-3 levels, upregulation of laminin and GAP-43, and downregulation of GFAP and CSPG proteins.