Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials.
Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials.
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DOI：
10.1016/j.actbio.2011.11.031
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发表时间：
2012-03
影响因子：
9.7
通讯作者：
Badylak, Stephen F.
中科院分区：
文献类型：
--
作者：
Brown, Bryan N.;Londono, Ricardo;Tottey, Stephen;Zhang, Li;Kukla, Kathryn A.;Wolf, Matthew T.;Daly, Kerry A.;Reing, Janet E.;Badylak, Stephen F.
巨噬细胞已被分类为具有可塑性表型，其存在于M1（经典活化;促炎）和M2（交替活化;调节，稳态）之间的谱内。迄今为止，主要在对病原体或癌症的反应的背景下研究了朝向M1或M2表型的极化的影响。最近，M1和M2巨噬细胞已被证明在损伤后的组织重塑中发挥不同的作用。在本研究中，利用M1/M2范例检查了巨噬细胞在大鼠腹壁植入14种生物衍生外科补片材料后重塑过程中的作用。检查了对材料响应的巨噬细胞的原位极化，并将其与所观察到的组织重塑响应的定量测量相关联，以确定巨噬细胞极化是否是生物支架促进建设性组织重塑的能力的准确预测因子。此外，M1和M2巨噬细胞在体外差异性募集祖细胞样细胞的能力（通常观察到参与具有积极临床结果的ECM支架的重塑）作为观察到的重塑反应差异的潜在可能机制进行了检查。本研究的结果表明，早期巨噬细胞对植入材料的反应与组织重塑的结果之间存在很强的相关性。第14天重塑部位内M2巨噬细胞数量增加和M2：M1巨噬细胞比率较高与更积极的重塑结果相关（r2=0.525-0.686，p<0.05）。此外，本研究的结果表明，建设性重塑的结果可能是由于不同的细胞群的招聘和生存与材料相关的重塑引起M1与M2的反应。M2和M0巨噬细胞条件培养基均显示出比M1巨噬细胞条件培养基更高的趋化活性（p<0.05）。对这些问题的更透彻的理解将在逻辑上影响下一代生物材料的设计和功能宿主组织形成的再生医学策略的发展。
Macrophages have been classified as having plastic phenotypes which exist within a spectrum between M1 (classically activated; pro-inflammatory) and M2 (alternatively activated; regulatory, homeostatic). To date, the effects of polarization towards a predominantly M1 or M2 phenotype have been studied largely in the context of response to pathogen or cancer. Recently, M1 and M2 macrophages have been shown to play distinct roles in tissue remodeling following injury. In the present study, the M1/M2 paradigm was utilized to examine the role of macrophages in the remodeling process following implantation of 14 biologically derived surgical mesh materials in the rat abdominal wall. In situ polarization of macrophages responding to the materials was examined and correlated to a quantitative measure of the observed tissue remodeling response to determine whether macrophage polarization is an accurate predictor of the ability of a biologic scaffold to promote constructive tissue remodeling. Additionally the ability of M1 and M2 macrophages to differentially recruit progenitor-like cells in vitro, which are commonly observed to participate in the remodeling of those ECM scaffolds which have a positive clinical outcome, was examined as a possible mechanism underlying the differences in the observed remodeling responses. The results of the present study show that there is a strong correlation between the early macrophage response to implanted materials and the outcome of tissue remodeling. Increased numbers of M2 macrophages and higher ratios of M2:M1 macrophages within the site of remodeling at 14 days were associated with more positive remodeling outcomes (r2=0.525–0.686, p<0.05). Further, the results of the present study suggest that the constructive remodeling outcome may be due to the recruitment and survival of different cell populations to the sites of remodeling associated with materials that elicit an M1 versus M2 response. Both M2 and M0 macrophage conditioned medias were shown to have higher chemotactic activities than media conditioned by M1 macrophages (p<0.05). A more thorough understanding of these issues will logically influence the design of next generation biomaterials and the development of regenerative medicine strategies for the formation of functional host tissues.
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影响因子：
14
作者：
Brown, Bryan N.;Barnes, Christopher A.;Kasick, Rena T.;Michel, Roger;Gilbert, Thomas W.;Beer-Stolz, Donna;Castner, David G.;Ratner, BuddyD.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
DOI：
10.1073/pnas.0905851106
发表时间：
2010-02-23
影响因子：
11.1
作者：
Agrawal, Vineet;Johnson, Scott A.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
14
作者：
Brown, Bryan N.;Valentin, Jolene E.;Stewart-Akers, Ann M.;McCabe, George P.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
14
作者：
Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
7.4
作者：
Deonarine K;Panelli MC;Stashower ME;Jin P;Smith K;Slade HB;Norwood C;Wang E;Marincola FM;Stroncek DF
通讯作者：
Stroncek DF