We previously described stem/progenitor cells with neural differentiation potential in leptomeninges of postnatal day 15 (P15) rats. Leptomeninges, which include arachnoid and pia mater, cover the entire central nervous system (CNS) and are filled with cerebrospinal fluid (CSF) produced by choroid plexi. Long-term maintenance of stem cells requires their migration and homing within supportive stem cell niches. These processes are mediated by recognition processes with extravascular tissue-specific structures and interaction with chemotactic factors. We found that leptomeninges of adult rats express important chemotactic factors, such as SDF-1, as well as several extracellular matrix components endowed of trophic functions, including laminin, fibronectin and agrin. Moreover, we found that nestin-positive cells in leptomeninges express CXCR4, the chemokine receptor specific for SDF-1. To further characterize leptomeninges as a stem cell niche, we analysed the homing and the distribution in the brain of adult rats of transplanted and in vitro-expanded leptomeningeal stem/progenitor cells (LeSC). Expanded leptomeningeal nestin-positive cells, derived from P15 EGFP-transgenic rats, were stereotaxically injected (3x103 EGFP+cells in 1µl) into the third ventriculus of adult rats (n=4) and observed by immunofluorescence confocal microscopy 4 weeks after transplantation. We found injected EGFP+/nestin+ cells in leptomeninges intermingled with resident nestin-positive cells. EGFP+ cells were also observed in the cortex parenchima. Most of these cells were negative for both nestin and the neural markers MAP2, GFAP and NG2; some EGFP+/MAP2-positive cells were found. Interestingly, some of the EGFP+ cells were found along blood vessels, located in the perivascular space,in close contact with astrocytes, and the lumen of vessels. At difference with intraventricular injection, in vitro-expanded EGFP+LeSC cells injected into the hippocampus expressed several neuronal markers including neurofilament, doublecortin, NeuN and Gad-67. Thus, adult neurogenic niches play a role in directing neuronal production. In conclusion, in vitro expanded leptomeninges-derived nestin-positive cells injected in adult brain retained stem cell features when located in the leptomeninges and differentiated into neurons when located in the brain parenchyma, further supporting the LeSC plasticity. These data suggest leptomeninges are a favourable microenvironment, or niche, capable of hosting stem/precursor cells.
Homing and migration of transplanted leptomeningeal stem/progenitor cells in adult rat brain
FUMAGALLI, Guido Francesco;DECIMO, Ilaria;BIFARI, Francesco;KRAMPERA, Mauro
2010-01-01
Abstract
We previously described stem/progenitor cells with neural differentiation potential in leptomeninges of postnatal day 15 (P15) rats. Leptomeninges, which include arachnoid and pia mater, cover the entire central nervous system (CNS) and are filled with cerebrospinal fluid (CSF) produced by choroid plexi. Long-term maintenance of stem cells requires their migration and homing within supportive stem cell niches. These processes are mediated by recognition processes with extravascular tissue-specific structures and interaction with chemotactic factors. We found that leptomeninges of adult rats express important chemotactic factors, such as SDF-1, as well as several extracellular matrix components endowed of trophic functions, including laminin, fibronectin and agrin. Moreover, we found that nestin-positive cells in leptomeninges express CXCR4, the chemokine receptor specific for SDF-1. To further characterize leptomeninges as a stem cell niche, we analysed the homing and the distribution in the brain of adult rats of transplanted and in vitro-expanded leptomeningeal stem/progenitor cells (LeSC). Expanded leptomeningeal nestin-positive cells, derived from P15 EGFP-transgenic rats, were stereotaxically injected (3x103 EGFP+cells in 1µl) into the third ventriculus of adult rats (n=4) and observed by immunofluorescence confocal microscopy 4 weeks after transplantation. We found injected EGFP+/nestin+ cells in leptomeninges intermingled with resident nestin-positive cells. EGFP+ cells were also observed in the cortex parenchima. Most of these cells were negative for both nestin and the neural markers MAP2, GFAP and NG2; some EGFP+/MAP2-positive cells were found. Interestingly, some of the EGFP+ cells were found along blood vessels, located in the perivascular space,in close contact with astrocytes, and the lumen of vessels. At difference with intraventricular injection, in vitro-expanded EGFP+LeSC cells injected into the hippocampus expressed several neuronal markers including neurofilament, doublecortin, NeuN and Gad-67. Thus, adult neurogenic niches play a role in directing neuronal production. In conclusion, in vitro expanded leptomeninges-derived nestin-positive cells injected in adult brain retained stem cell features when located in the leptomeninges and differentiated into neurons when located in the brain parenchyma, further supporting the LeSC plasticity. These data suggest leptomeninges are a favourable microenvironment, or niche, capable of hosting stem/precursor cells.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
