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

Abstract

Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC-and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome.

Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction

“…These observations are consistent with previous studies in which angiogenesis and neurogenesis were accelerated along with neurologic recovery in animal models of stroke after cell transplantation with MSCs [62] and HSCs [33]. In addition, we found that an increase in CBF correlated with reduction in locomotion during the light phase.…”

Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury

“…In our study, transplanted MSC migrated to the neighborhood of the injured spinal cord, but did not differentiate into glial or neuronal elements. Current thinking is that the potential beneficial effects of MSC in SCI are not related to neuronal or glial differentiation of MSC, but rather from their secretion of growth factors and/or cytokines (Sasaki et al, 2009), which can provide neuroprotection (Chen et al, 2002;Parr et al, 2007), induction of axonal sprouting (Shen et al, 2006), neovascularization (Onda et al, 2008), and immunomodulation (Ohtaki et al, 2008;Bai et al, 2009). MSC may also promote axonal regeneration or encourage functional plasticity by establishing an environment that supports axonal growth, for example, by abrogating the inhibitory influence of the chondroitin sulfated proteoglycans (CSPG), and/or myelin debris present in the injury site and glial scar (Wright et al, 2011).…”

The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

“…Recent data show that administration of MSC after a HI insult significantly reduces lesion volume, improves behavioral performance, and promotes neurogenesis. 35,[125][126][127] Furthermore, studies show that MSCs migrate to the ischemic boundary zone where they induce changes in brain environment that promote and support neurogenesis. [128][129][130] A study from our group showed that intracranial MSC treatment at 3 and 10 days after HI-induced injury changes the expression of genes involved in regenerative processes.…”