Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis.
Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis.
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DOI：
10.1016/j.yexcr.2011.01.018
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发表时间：
2011-04-01
影响因子：
3.7
通讯作者：
McLoon LK
中科院分区：
文献类型：
--
作者：
Kallestad KM;Hebert SL;McDonald AA;Daniel ML;Cu SR;McLoon LK
眼外肌(EOM)在衰老和多种形式的肌营养不良症中免受病理影响。尽管有许多研究，但这种节制仍然是一个谜。与体节来源的肌肉相比，EOM具有明显的胚胎谱系，我们已经证明，它们在一生中不断重塑，即使在衰老过程中也保持着激活的卫星细胞的数量。这一数据表明，EOM中存在与肢体不同的成肌前体细胞(MPC)群体，与肢体MPC相比，EOM中的干细胞和/或具有更强增殖能力的MPC数量增加。用流式细胞术比较了EOM和四肢肌肉单个核细胞，发现了一些差异。使用两种不同的细胞分离方法，EOM每毫克肌肉的MPC明显多于四肢骨骼肌。CD34表达阳性，SCA-1、M-钙粘蛋白、CD31和CD45表达阴性。我们将其命名为EOMCD34细胞。EOMCD34细胞在新生儿EOM和四肢肌肉中的比例相似。此外，它们在老年EOM中被保留，而在成人四肢肌肉中数量显著减少，在老年四肢肌肉中极其稀少。最重要的是，在dmdx和mdx/utroin−/−(Dko)模型鼠的EOM中，EOMCD34细胞的百分比都升高，而这些小鼠的四肢肌肉中的EOMCD34细胞极其稀少。在体外，EOMCD34细胞具有肌细胞分化潜能，在分化介质中形成肌管。在确定了能够更好地诱导这些细胞增殖的培养基后，计算了融合指数。从EOM分离的细胞与从四肢肌肉分离的细胞相比，融合指数高40%。EOMCD34细胞对氧化应激和机械损伤均具有抵抗能力。这些数据支持我们的假设，即EOM可能在衰老和肌肉营养不良中幸免于难，这是由于MPC的亚群，EOMCD34细胞在正常、MDX和DKO小鼠EOM中保留的百分比明显更高，似乎对高水平的氧化应激和毒素具有抵抗力，并在整个生命过程中活跃地增殖。目前的研究集中在进一步从分子上定义EOMCD34细胞亚型，希望这可能有助于揭示一种具有潜在治疗作用的细胞类型，用于治疗石棺减少症、恶病质或肌营养不良患者。
The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a population of activated satellite cells even in aging. This data suggested the hypothesis that there is a population of myogenic precursor cells (mpcs) in EOM that is different from those in limb, with either elevated numbers of stem cells and/or mpcs with superior proliferative capacity compared to mpcs in limb. Using flow cytometry, EOM and limb muscle mononuclear cells were compared, and a number of differences were seen. Using two different cell isolation methods, EOM have significantly more mpcs per mg muscle than limb skeletal muscle. One specific subpopulation significantly increased in EOM compared to limb was positive for CD34 and negative for Sca-1, M-cadherin, CD31, and CD45. We named these the EOMCD34 cells. Similar percentages of EOMCD34 cells were present in both newborn EOM and limb muscle. In addition, they were retained in aged EOM, whereas the population decreased significantly in adult limb muscle and were extremely scarce in aged limb muscle. Most importantly, the percentage of EOMCD34 cells were elevated in the EOM from both the mdx and the mdx/utrophin−/− (DKO) mouse models of DMD and extremely scarce in the limb muscles of these mice. In vitro, the EOMCD34 cells had myogenic potential, forming myotubes in differentiation media. After determining a media better able to induce proliferation in these cells, a fusion index was calculated. The cells isolated from EOM had a 40% higher fusion index compared to the same cells isolated from limb muscle. The EOMCD34 cells were resistant to both oxidative stress and mechanical injury. These data support our hypothesis that the EOM may be spared in aging and in muscular dystrophies due to a subpopulation of mpcs, the EOMCD34 cells, that are retained in significantly higher percentages in normal, mdx and DKO mice EOM, appear to be resistant to elevated levels of oxidative stress and toxins, and actively proliferate throughout life. Current studies are focused on further defining the EOMCD34 cell subtype molecularly, with the hopes that this may shed light on a cell type with potential therapeutic use in patients with sarcopenia, cachexia, or muscular dystrophy.
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影响因子：
5.6
作者：
Kallestad, Kristen M.;McLoon, Linda K.
通讯作者：
McLoon, Linda K.
影响因子：
2.8
作者：
Decary, S;Ben Hamida, C;Butler-Browne, GS
通讯作者：
Butler-Browne, GS
影响因子：
64.5
作者：
Grady, RM;Teng, HB;Sanes, JR
通讯作者：
Sanes, JR
影响因子：
9.9
作者：
Chen, YW;Nagaraju, K;Hoffman, EP
通讯作者：
Hoffman, EP
影响因子：
9.9
作者：
HORTON, RM;MANFREDI, AA;CONTITRONCONI, BM
通讯作者：
CONTITRONCONI, BM