不同劑量的骨髓間充質干細胞移植與改善缺血心臟功能的量效關系_《中國胸心血管外科臨床雜志》

作者：

張雷楊 , 陳鑫 , 徐順霖等

南京醫科大學附屬南京第一醫院南京市心血管病研究所心胸外科, 南京 210006;

關鍵詞：

骨髓間充質干細胞細胞移植心肌缺血細胞劑量

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目的探討不同劑量的骨髓間充質干細胞移植梗死的心肌與改善缺血心臟功能的量效關系。方法結扎F344大鼠的冠狀動脈，制作大鼠心肌梗死模型，于模型建立1周后將32只大鼠采用隨機數字表法分為4組，每組8只。將經5-溴脫氧尿苷（BrdU）標記的不同劑量的骨髓間充質干細胞，分別為1×103個（組1) 、1×105個（組2) 、1×107個（組3）注入心肌缺血區；對照組注射等量的無血清IMDM。于模型建立前、細胞移植前和細胞移植后4周采用超聲心動圖檢測射血分數(EF). 細胞移植后4周行BrdU、閏盤連接蛋白（Connexin43) 、肌球蛋白重鏈β (MHC) 、平滑肌肌動蛋白α (α-SMA）的免疫組織化學染色。計數α-SMA著色的功能小血管數量。結果細胞移植后4周，組1 EF與對照組比較差異無統計學意義(0.34±0.16 vs. 0.36±0.15,P gt;0.05)，組2 EF較組1明顯增高(0.54±0.20 vs. 0.34±016, P＝0.004)，組3 EF較組2明顯增高(0.71±0.24 vs. 0.54±0.20,P＝0.018)。細胞移植后4周，組2 BrdU和MHC雙陽性的細胞個數明顯多于組1 (323.20±91.62個/高倍視野vs. 51.75±27.58個/高倍視野,P＝0049)，組3的細胞個數明顯多于組2(409.75±106.65個/高倍視野vs. 323.20±91.62個/高倍視野,P lt;0.001), 對照組為0±0個/高倍視野。組1、組2和組3大部分移植細胞MHC、Connexin43染色呈陽性，心肌缺血區內可見大量α-SMA抗體,部分形態不規則。對照組和組1梗死區域有新生血管形成，組2較組1增多（28.38±1279個/高倍視野vs. 2275±9.07個/高倍視野,P＝0.015) ，組3較組2增多（35.63±13.27個/高倍視野vs. 28.38±12.79個/高倍視野,P＝0002) . 結論骨髓間充質干細胞移植能明顯改善缺血心臟的功能，且心肌細胞新生和心功能改善的程度均呈現移植細胞劑量依賴性。

引用本文： 張雷楊,陳鑫,徐順霖等. 不同劑量的骨髓間充質干細胞移植與改善缺血心臟功能的量效關系. 中國胸心血管外科臨床雜志, 2007, 14(6): 447-. doi: 復制

1.	Orlic D, Kajstura J, Chimenti S, et al.Bone marrow cells regenerate infarcted myocardium. Nature, 2001, 410 (6829) :701-705.
2.	朱洪生,黃日太,連鋒,等.骨髓間質干細胞移植對香豬急性心肌梗死后心肌結構和心功能的影響.中國胸心血管外科臨床雜志,2004,11(2):112-115.
3.	連鋒,朱洪生,薛松,等. 自體內皮祖細胞移植對急性心肌梗死近、中期心肌收縮力的影響. 中國胸心血管外科臨床雜志,2006,13(5):326-330.
4.	Agbulut O, Menot ML, Li Z, et al. Temporal patterns of bone marrow cell differentiation following transplantation in doxorubicin-induced cardiomyopathy. Cardiovasc Res,2003, 58(2):451-459.
5.	Behfar A,Terzic A. Derivation of a cardiopoietic population from human mesenchymal stem cells yields cardiac progeny. Nat Clin Pract Cardiovasc Med,2006,3(Suppl 1):S78-S82.
6.	Briguori C, Reimers B, Sarais C, et al. Direct intramyocardial percutaneous delivery of autologous bone marrow in patients with refractory myocardial angina. Am Heart J, 2006,151(3):674-680.
7.	Bittira B, Kuang JQ, Al-Khaldi A, et al. In vitro preprogramming of marrow stromal cells for myocardial regeneration. Ann Thorac Surg, 2002,74(4):1154-1159.
8.	Rangappa S, Entwistle J, Wechsler AS, et al. Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype. J Thorac Cardiovasc Surg,2003, 126(1):124-132.
9.	Shake JG, Gruber PJ, Baumgartner WA, et al. Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg, 2002, 73(6):1919-1925.
10.	Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 2002, 106(15):1913-1918.
11.	Assmus B, Schchinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation, 2002, 106(24):3009-3017.
12.	Wang JS, Shun-Tim D, Galipeau J, et al. Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. J Thorac Cardiovasc Surg, 2000, 120(5):999-1005.
13.	Zhang S, Wang D, Estrov Z, et al. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation, 2004,110(25):3803-3807.
14.	Anderson DJ, Gage FH, Weissman IL.Can stem cells cross lineage boundaries? Nat Med, 2001, 7(4):393-395.
15.	Matsumoto K, Yoshitomi H, Rossant J, et al. Liver organogenesis promoted by endothelial cells prior to vascular function. Science,? 2001,294(5542):559-563.
16.	Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels. Science, 2001,294(5542):564-567.

1. 　Orlic D, Kajstura J, Chimenti S, et al.Bone marrow cells regenerate infarcted myocardium. Nature, 2001, 410 (6829) :701-705.
2. 　朱洪生,黃日太,連鋒,等.骨髓間質干細胞移植對香豬急性心肌梗死后心肌結構和心功能的影響.中國胸心血管外科臨床雜志,2004,11(2):112-115.
3. 　連鋒,朱洪生,薛松,等. 自體內皮祖細胞移植對急性心肌梗死近、中期心肌收縮力的影響. 中國胸心血管外科臨床雜志,2006,13(5):326-330.
4. 　Agbulut O, Menot ML, Li Z, et al. Temporal patterns of bone marrow cell differentiation following transplantation in doxorubicin-induced cardiomyopathy. Cardiovasc Res,2003, 58(2):451-459.
5. 　Behfar A,Terzic A. Derivation of a cardiopoietic population from human mesenchymal stem cells yields cardiac progeny. Nat Clin Pract Cardiovasc Med,2006,3(Suppl 1):S78-S82.
6. 　Briguori C, Reimers B, Sarais C, et al. Direct intramyocardial percutaneous delivery of autologous bone marrow in patients with refractory myocardial angina. Am Heart J, 2006,151(3):674-680.
7. 　Bittira B, Kuang JQ, Al-Khaldi A, et al. In vitro preprogramming of marrow stromal cells for myocardial regeneration. Ann Thorac Surg, 2002,74(4):1154-1159.
8. 　Rangappa S, Entwistle J, Wechsler AS, et al. Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype. J Thorac Cardiovasc Surg,2003, 126(1):124-132.
9. 　Shake JG, Gruber PJ, Baumgartner WA, et al. Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg, 2002, 73(6):1919-1925.
10. 　Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 2002, 106(15):1913-1918.
11. 　Assmus B, Schchinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation, 2002, 106(24):3009-3017.
12. 　Wang JS, Shun-Tim D, Galipeau J, et al. Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. J Thorac Cardiovasc Surg, 2000, 120(5):999-1005.
13. 　Zhang S, Wang D, Estrov Z, et al. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation, 2004,110(25):3803-3807.
14. 　Anderson DJ, Gage FH, Weissman IL.Can stem cells cross lineage boundaries? Nat Med, 2001, 7(4):393-395.
15. 　Matsumoto K, Yoshitomi H, Rossant J, et al. Liver organogenesis promoted by endothelial cells prior to vascular function. Science,? 2001,294(5542):559-563.
16. 　Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels. Science, 2001,294(5542):564-567.

《中國胸心血管外科臨床雜志》

不同劑量的骨髓間充質干細胞移植與改善缺血心臟功能的量效關系

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《中國胸心血管外科臨床雜志》

不同劑量的骨髓間充質干細胞移植與改善缺血心臟功能的量效關系

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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