Activation of Notch signaling during ex vivo expansion maintains donor muscle cell engraftment.
Activation of Notch signaling during ex vivo expansion maintains donor muscle cell engraftment.
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DOI：
10.1002/stem.1181
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发表时间：
2012-10
期刊：
影响因子：
5.2
通讯作者：
Tapscott, Stephen J.
中科院分区：
文献类型：
--
作者：
Parker, Maura H.;Loretz, Carol;Tyler, Ashlee E.;Duddy, William J.;Hall, John K.;Olwin, Bradley B.;Bernstein, Irwin D.;Storb, Rainer;Tapscott, Stephen J.
肌源性干细胞移植对营养不良肌肉的长期修复具有巨大的潜力。然而，单一的供体肌肉活检不太可能提供足够的细胞来有效地移植肌肉萎缩症患者的肌肉。使用传统的体外培养技术进行细胞扩增，显著降低了移植的潜力。我们假设在体外扩增过程中Notch信号的激活将维持供体细胞的植入潜力。在这项研究中，我们将新分离的犬肌肉来源细胞扩展到包被Delta - 1ext - IgG的组织培养板上，以激活Notch信号，或者用人IgG作为对照。采用犬-鼠异种移植模型定量比较犬肌肉细胞移植，并确定移植的供体细胞是否能在体内作为卫星细胞发挥作用。我们发现，δ - 1ext - IgG抑制犬肌源性细胞的分化，并增加了在肌源性前体中正常表达的基因水平。此外，与在人IgG上扩增的细胞相比，在δ - 1ext - IgG上扩增的细胞导致供体来源纤维的数量显著增加，达到与新分离细胞相似的移植水平。重要的是，细胞在移植到受体卫星细胞壁龛上的δ - 1ext - IgG上扩增，并有助于进一步再生。在Notch配体上扩展人类肌肉来源细胞的类似策略可能有助于肌肉萎缩症患者的植入和肌肉再生。干细胞2012；30:2212 - 2220
Transplantation of myogenic stem cells possesses great potential for long‐term repair of dystrophic muscle. However, a single donor muscle biopsy is unlikely to provide enough cells to effectively transplant the muscle mass of a patient affected by muscular dystrophy. Expansion of cells ex vivo using traditional culture techniques significantly reduces engraftment potential. We hypothesized that activation of Notch signaling during ex vivo expansion would maintain donor cell engraftment potential. In this study, we expanded freshly isolated canine muscle‐derived cells on tissue culture plates coated with Delta‐1ext‐IgG to activate Notch signaling or with human IgG as a control. A model of canine‐to‐murine xenotransplantation was used to quantitatively compare canine muscle cell engraftment and determine whether engrafted donor cells could function as satellite cells in vivo. We show that Delta‐1ext‐IgG inhibited differentiation of canine muscle‐derived cells and increased the level of genes normally expressed in myogenic precursors. Moreover, cells expanded on Delta‐1ext‐IgG resulted in a significant increase in the number of donor‐derived fibers, as compared to cells expanded on human IgG, reaching engraftment levels similar to freshly isolated cells. Importantly, cells expanded on Delta‐1ext‐IgG engrafted to the recipient satellite cell niche and contributed to further regeneration. A similar strategy of expanding human muscle‐derived cells on Notch ligand might facilitate engraftment and muscle regeneration for patients affected with muscular dystrophy. Stem Cells 2012;30:2212–2220
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影响因子：
11.8
作者：
Conboy, IM;Rando, TA
通讯作者：
Rando, TA
影响因子：
7.8
作者：
Lindon, C;Montarras, D;Pinset, C
通讯作者：
Pinset, C
DOI：
10.1083/jcb.200405004
发表时间：
2004-09-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Engler AJ;Griffin MA;Sen S;Bönnemann CG;Sweeney HL;Discher DE
通讯作者：
Discher DE
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM
影响因子：
20.3
作者：
Varnum-Finney, B;Brashem-Stein, C;Bernstein, ID
通讯作者：
Bernstein, ID