کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2101897 1546276 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel Strategy for Successful Long-Term Hematopoietic Recovery after Transplanting a Limited Number of Hematopoietic Stem/Progenitor Cells
ترجمه فارسی عنوان
استراتژی نوین برای بازیابی هماتوپوئیت بلند مدت پس از پیوند یک تعداد محدودی از سلول های بنیادی / پیش ساز هماتوپوئیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی

Various investigators have attempted to overcome the shortage of available hematopoietic stem/progenitor cells (HSPCs) by facilitating their engraftment after transplantation. Preconditioning of HSPCs with the granulocyte-derived cationic peptide LL-37 has been suggested as a useful strategy to facilitate engraftment of transplanted cells by enhancing their responsiveness to CXCL12. In this study, we evaluated whether LL-37 preconditioning is acceptable for clinical application. We found that the effect of LL-37 preconditioning was specific to clonogenic cells and was mediated specifically by increased calcium influx with the activation of downstream signaling through mammalian target of rapamycin complex 1 (mTORC1). Because hyperactivation of mTORC1 and the disruption of 5′ adenosine monophosphate-activated protein kinase (AMPK) are known to deplete HSPC pools, we compared the repopulation capacity of HSPCs preconditioned with LL-37 and those preconditioned with AMPK activator (AICAR). In vivo competitive repopulation experiments revealed that LL-37 preconditioning impairs long-term repopulation of transplanted HSPCs, suggesting that this strategy might not acceptable for clinical applications in which long-term repopulation capacity is a prerequisite. AICAR preconditioning dramatically enhanced the long-term repopulation of transplanted HSPCs, however. Taken together, these results suggest that future strategies to ensure successful transplantation outcomes should focus on protecting HSPCs from various stimuli during their homing to the bone marrow niches rather than activating them before transplantation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 20, Issue 9, September 2014, Pages 1282–1289
نویسندگان
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