人间充质干细胞横向分化为造血干细胞的分子机制和临床应用

摘要

There is little evidence that mesenchymal stem cells (MSCs) can transdifferentiate into hematopoietic stem cells (HSCs). Herein we demonstrate that transfection of two smlall RNAs (sRNA) for two days is sufficient to trigger adipose-derived mesenchymal stem cells (AD-MSCs) to transdifferentiate into hematopoietic stem cells (HSCs) on a large-scale. These adipose-derived HSCs (AD-HSCs) are capable of efficient expansion ex vivo by approximately 100 fold for CD34+/CD133+ cells in the presence of specific cytokines. Furthermore, AD-HSCs could exhibit hematopoietic precursor cell phenotypes and genotypes, and in vitro or in vivo potential for differentiation into multi-lineages of blood cells including lymphocytes, granulocytes, erythrocytes, megakaryocytes, and monocytes, as did naturally-occurring HSCs. Moreover, analysis of global gene expression profiling and PCR results demonstrated that EID1 knockdown resulted in activation of adult hematopoietic programs. The concept of AD-HSCs could aid development of therapies for blood diseases and the fabrication of MSC-based blood.

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