Long-term bone marrow culture and its clinical potential in chronic wound healing
Long-term bone marrow culture and its clinical potential in chronic wound healing
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DOI：
10.1111/j.1524-475x.2007.00305.x
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发表时间：
2007-11-01
影响因子：
2.9
通讯作者：
Maizel, Abby
中科院分区：
文献类型：
--
作者：
Badiavas, Evangelos V.;Ford, Dwayne;Maizel, Abby
长期以来，人们一直认为骨髓来源的细胞在皮肤的稳态中起着至关重要的作用。我们之前已经描述了直接应用自体骨髓抽吸和培养骨髓细胞治疗顽固性慢性皮肤伤口的临床益处。对治疗的最初反应似乎是血管性质的，形成了新的血管。然而，持续培养足够数量的细胞以输送给患者的困难是一个限制因素。在这里，在随后的方案中，我们描述了一种改进的骨髓培养系统，产生可靠的骨髓细胞生长，并导致更大的临床反应。表达内皮祖细胞标志物（包括CD133、CD146，特别是CD14）的细胞在这些培养中增强。cd14分离的细胞在内皮细胞实验中产生集落，在基质实验中发芽。血管生成细胞因子，包括血管生成素、上皮中性粒细胞活化蛋白-78、生长调节癌基因、生长调节癌基因- α、白细胞介素-8、CXC16和单核细胞趋化蛋白-1，在这些培养物中被发现升高。改良培养细胞用于慢性伤口患者，治疗时间长达10 ~ 10年，可提高临床疗效。
Bone marrow-derived cells have long been regarded to play a crucial role in the homeostasis of skin. We have previously described the clinical benefit of directly applying autologous bone marrow aspirate and cultured bone marrow cells to recalcitrant chronic skin wounds. The initial response to treatment appears to be vascular in nature with the formation of new blood vessels. The difficulty in consistently growing adequate numbers of cells for delivery to patients was, however, a limiting factor. Here, in a subsequent protocol, we describe an improved bone marrow culture system yielding a reliable growth of bone marrow cells and leading to a greater clinical response. Cells expressing markers of endothelial progenitors including CD133, CD146, and particularly CD14 are enhanced in these cultures. CD14-isolated cells produced colonies in endothelial cell assays and sprouting in matrigel assays. Angiogenic cytokines, including angiogenin, epithelial neutrophil-activating protein-78, growth-regulated oncogene, growth-regulated oncogene-alpha, Interleukin-8, CXC16, and monocyte chemoattractant protein-1, were found to be elevated in these cultures. Administration of improved culture cells to patients with chronic wounds present for > 1 year lead to an enhanced clinical response.