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Effects of amyloid precursor protein peptide APP96-110,alone or with human mesenchymal stromal cells,on recovery after spinal cord injury

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Neural Regeneration Research 2022年第6期17卷 1376-1386页

作者： Stuart I.Hodgetts Sarah J.Lovett D.Baron-Heeris a.fogliani Marian Sturm C.Van den Heuvel Alan R.Harvey School of Human Sciences The University of Western Australia(UWA)PerthWAAustralia Perron Institute for Neurological and Translational Science PerthWAAustralia Cell and Tissue Therapies WA(CTTWA) Royal Perth HospitalPerthWAAustralia Adelaide Medical School Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSAAustralia

Delivery of a peptide(APP96-110),derived from amyloid precursor protein(APP),has been shown to elicit neuroprotective effects following cerebral stroke and traumatic brain *** this study,the effect of APP96-110 or a mutant version of this peptide(mAPP96-110)was assessed following moderate(200 kdyn,(2 N))thoracic contusive spinal cord injury(SCI)in adult Nude *** received a single tail vein injection of APP96-110 or mAPP96-110 at 30 minutes post-SCI and were then assessed for functional improvements over the next 8 weeks.A cohort of animals also received transplants of either viable or non-viable human mesenchymal stromal cells(hMSCs)into the SC lesion site at one week post-injury to assess the effect of combining intravenous APP96-110 delivery with hMSC *** were perfused 8 weeks post-SCI and longitudinal sections of spinal cord analyzed for a number of factors including hMSC viability,cyst size,axonal regrowth,glial reactivity and macrophage *** of sensorimotor function revealed occasional significant differences between groups using Ladderwalk or Ratwalk tests,however there were no consistent improvements in functional outcome after any of the ***96-110 alone,and APP96-110 in combination with both viable and non-viable hMSCs significantly reduced cyst size compared to SCI *** treatments with donor hMSCs also significantly increased βIII tubulin^(+),glial fibrillary acidic protein(GFAP^(+))and laminin+expression,and decreased ED1^(+)expression in *** preliminary study demonstrates that intravenous delivery of APP96-110 peptide has selective,modest neuroprotective effects following SCI,which may be enhanced when combined with hMSC ***,the effects are less pronounced and less consistent compared to the protective morphological and cognitive impact that this same peptide has on neuronal survival and behaviour after stroke and traumatic brain *** while the efficacy of a

关键词： amyloid precursor protein cell transplantation combination contusion functional recovery mesenchymal stromal cells neuroprotection regeneration spinal cord injury tissue sparing

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