RESUMEN
Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing.
Asunto(s)
Encéfalo/fisiopatología , Sangre Fetal/citología , Leucocitos Mononucleares/trasplante , Recuperación de la Función/fisiología , Accidente Cerebrovascular/terapia , Animales , Encéfalo/patología , Criopreservación , Modelos Animales de Enfermedad , Humanos , Leucocitos Mononucleares/citología , Imagen por Resonancia Magnética , Ratas , Ratas Endogámicas SHR , Accidente Cerebrovascular/fisiopatología , Resultado del TratamientoRESUMEN
Ectomycorrhiza (EM) formation improves tree growth and nutrient acquisition, particularly that of nitrogen (N). Few studies have coupled the effects of naturally occurring EM morphotypes to the nutrition of host trees. To investigate this, pine seedlings were grown on raw humus substrates collected at two forest sites, R2 and R3. Ectomycorrhiza morphotypes were identified, and their respective N uptake rates from organic (2-(13)C, (15)N-glycine) and inorganic ((15)NH(4)Cl, Na(15)NO(3), (15)NH(4)NO(3), NH(4)(15)NO(3)) sources as well as their phosphate uptake rates were determined. Subsequently, the growth and nutritional status of the seedlings were analyzed. Two dominant EM morphotypes displayed significantly different mycorrhization rates in the two substrates. Rhizopogon luteolus Fr. (RL) was dominant in R2 and Suillus bovinus (Pers.) Kuntze (SB) was dominant in R3. (15)N uptake of RL EM was at all times higher than that of SB EM. Phosphate uptake rates by the EM morphotypes did not differ significantly. The number of RL EM correlated negatively and the number of SB EM correlated positively with pine growth rate. Increased arginine concentrations and critical P/N ratios in needles indicated nutrient imbalances of pine seedlings from humus R2, predominantly mycorrhizal with RL. We conclude that different N supply in raw humus under Scots pine stands can induce shifts in the EM frequency of pine seedlings, and this may lead to EM formation by fungal strains with different ability to support tree growth.