Adipose Tissue-Derived Mesenchymal Stem Cells Facilitate Hematopoiesis in Vitro and in Vivo Advantages Over Bone Marrow-Derived Mesenchymal Stem Cells
Adipose Tissue-Derived Mesenchymal Stem Cells Facilitate Hematopoiesis in Vitro and in Vivo Advantages Over Bone Marrow-Derived Mesenchymal Stem Cells
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DOI：
10.2353/ajpath.2010.091042
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发表时间：
2010-08-01
影响因子：
6
通讯作者：
Naoe, Tomoki
中科院分区：
文献类型：
--
作者：
Nakao, Norihiko;Nakayama, Takayuki;Naoe, Tomoki
间充质干细胞（MSCs）已成为一种新的治疗方式，通过改善干细胞移植的植入来重建造血微环境。然而，传统骨髓来源的间充质干细胞（BMSCs）的可用性是有限的。最近的研究表明，可以很容易地从脂肪组织中分离出大量的间充质干细胞（adipose tissue-derived MSCs [ADSCs]）。在这项研究中，我们广泛评估了ADSCs的造血支持特性，这在很大程度上是未知的。体外共培养和祖细胞实验表明，ADSCs比BMSCs产生更多的人造血干细胞（hsc）的粒细胞和祖细胞。我们发现，ADSCs表达趋化因子CXCL12，这是造血的关键调节因子，其水平比BMSCs高3倍。添加CXCL12受体拮抗剂导致ADSC层的粒细胞产量降低，而在BMSC共培养中添加重组CXCL12促进了粒细胞的生长。体内细胞归巢实验表明，ADSCs比BMSCs更能促进小鼠造血干细胞向基底细胞的归巢。将ADSCs注射到致死性辐照小鼠的骨髓腔中，比BMSCs更快地重建了造血功能，并随后挽救了接受少量hsc的小鼠。二次移植实验表明，ADSCs对长期造血干细胞有良好的作用。这些结果表明，ADSCs可以作为骨髓间充质干细胞的一种有前景的治疗替代品。（美国病理学杂志，2010,177:547-554;DOI: 10.2353/ajpath.2010.091042）
Mesenchymal stem cells (MSCs) have emerged as a new therapeutic modality for reconstituting the hematopoietic microenvironment by improving engraftment in stem cell transplantation. However, the availability of conventional bone marrow (BM)-derived MSCs (BMSCs) is limited. Recent studies showed that a large number of MSCs can be easily isolated from fat tissue (adipose tissue-derived MSCs [ADSCs]). In this study, we extensively evaluated the hematopoiesis-supporting properties of ADSCs, which are largely unknown. In vitro coculture and progenitor assays showed that ADSCs generated significantly more granulocytes and progenitor cells from human hematopoietic stem cells (HSCs) than BMSCs. We found that ADSCs express the chemokine CXCL12, a critical regulator of hematopoiesis, at levels that are three fold higher than those with BMSCs. The addition of a CXCL12 receptor antagonist resulted in a lower yield of granulocytes from ADSC layers, whereas the addition of recombinant CXCL12 to BMSC cocultures promoted the growth of granulocytes. vivo cell homing assays showed that ADSCs facilitated the homing of mouse HSCs to the BM better than BMSCs. ADSCs injected into the BM cavity of fatally irradiated mice reconstituted hematopoiesis more promptly than BMSCs and subsequently rescued mice that had received a low number of HSCs. Secondary transplantation experiments showed that ADSCs exerted favorable effects on long-term HSCs. These results suggest that ADSCs can be a promising therapeutic alternative to BMSCs. (Am J Pathol 2010, 177:547-554; DOI: 10.2353/ajpath.2010.091042)