维进,等剧源干细胞在组织工程和再生医学的应用 Www.crter. org 是否能从人体组织中分离得到具有单一确切标记物[9 Qu-Petersen Z. Deasy B, Jankowski R,etal. Identification of a novel population of muscle stem cells in mice: potential for 的肌源干细胞细胞群,如何调节体内微环境诱导肌源 muscle regeneration. J Cell Biol. 2002: 157(5): 851-864 千细胞定向分化,如何调控肌源干细胞与受区周围细10 Gallacher L, Murdoch B, Wu DM,etal. Isolation and 胞之间的相互作用,如何深入了解肌源干细胞移植后 characterization of human CD34(-)Lin(-)and CD34(+) Lin(-) hematopoietic stem cells using cell surface markers AC 133 与性别相关的差异表现,如何通过更为精准的基因学 and cD7Bood.200095(9)28132820 方法调控肌源干细胞的命运,这些都是肌源干细胞研 Oshima H, Payne TR, Urish KL, et al. Differential myocardial with muscle stem cells c 究必须面临的问题。肌源干细胞诸多的优势已经表现 Mol Ther.2005;12(6):1130-1141 为其在组织工程学和再生医学研究和临床尝试治疗[12] Claros s, Alonso M, Becerra j, et al. Selection and induction 临床应用,有赖于以上问题的解决和肌源干细胞分化13 Musgrave DS, Bosch P, Lee JY, et al0856010 方面的广泛应用,然而,最终将之安全有效的推广到 of rat skeletal muscle-derived cells to the chondro-osteo lineage Cell Mol Biol(Noisy-le-grand). 20 调控机制的深度阐明 produce bone using different cell types. Clin Orthop Relat Res. 2000;(378)290-305. [14] Wright V, Peng H, Usas A, et al. BMP4-expressing 作者贡献:第一、二作者进行实验实施,第三作者进 muscle-derived stem cells differentiate into osteogenic 行实验评估,成文为第一作者,第三作者进行实验设计与 ineage and improve bone healing in immunocompetent mice Mol Ther.20026(2):169-178 审校,第一作者对文章负责。 [15 Corsi KA, Pollett JB, Phillippi JA, et al. Osteogenic potential of 利益冲突:课题未涉及任何厂家及相关雇主或其他经 postnatal skeletal muscle-derived stem cells is influenced by 济组织直接或间接的经济或利益的赞助。 donor sex. J Bone Miner Res 2007: 22(10): 1592-1602 [16] Peng H, Usas A, Gearhart B, et al. Development of a 伦理要求:未涉及伦理问题 elf-inactivating tet-on retroviral vector expressing bone 作者声明:文章为原创作品,内容不涉及泄密,无 morphogenetic protein 4 to achieve regulated bone formation 稿两投,无抄袭,无内容剽窃,无作者署名争议,无与他7Le. Musgrave D, Pelinkovic D. et al. Effect of bone 人课题以及专利技术的争执,内容真实,文责自负。 morphogenetic protein-2-expressing muscle-derived cells Surg Am.2001:83A(7:1032-1039 4参考文献 [18] Adachi N, Sato K, Usas A, et al. Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular [1] Katz B The terminations of the afferent nerve fibre in the cartilage defects. J Rheumatol. 2002: 29(9): 1920-1930 muscle spindles of the frog. Philos Trans R Soc Lond B Biol [19] Kuroda R, Usas A, Kubo S, et al. Cartilage repair using bone sci.1961243:221-240 morphogenetic protein 4 and muscle-derived stem cells [2] Yu M, Zhang C, Zhang Y, et al. BM stem cell transplantation thritis rheum.2006:54(2)433-442 rescues pathophysiologic features of aged dystrophic mdx [20] Lee JY, Cannon TW, Pruchnic R, et al. The effects of muscle Cytotherapy. 2007, 9(1): 44-52 periurethral muscle-derived stem cell injection on leak point [3] Bhagavati S, Xu W. Isolation and enrichment of skeletal pressure in a rat model of stress urinary incontinence. Int muscle progenitor cells from mouse bone marrow. Biochem Urogynecol J Pelvic Floor Dysfunct. 2003; 14(1): 31-37 Biophys Res Commun. 2004: 318(1): 119-124 [21] Huard J, Yokoyama T, Pruchnic R, et al. Muscle-derived [4] Seale P, Sabourin LA, Girgis-Gabardo A, et al. Pax7 is cell-mediated ex vivo gene therapy for urological dysfunction required for the specification of myogenic satellite cells. Cel Gene Ther.2002;9(23):1617-1626 2000;102(6):777-786 [22] Proano AR, Medrano A, Garrido G, et al. Muscle-derived sten 15] Qu Z, Huard J Matching host muscle and donor myoblasts for cell therapy for stress urinary incontinence. Actas Urol Esp myosin heavy chain improves myoblast transfer therapy 2010:34(1):15-23 [23 Vadala G, Sobajima S, Lee JY, et al. In vitro interaction [6] Arsic N, Mamaeva D, Lamb NJ, et al. Muscle-derived stem between muscle-derived stem cells and nucleus pulposus cells isolated as non-adherent population give rise to cardiac keletal muscle and neural lineages. Exp Cell Res 2008 [24] Schultz SS, Lucas PA Human stem cells isolated from adult 314(6):1266-1280 skeletal muscle differentiate into neural phenotypes. J [7 Seale P, Rudnicki MA. A new look at the origin, function, and Neurosci methods.2006:152(1-2:144-155 stem-cell status of muscle satellite cells. Dev biol. 2000 [25]Tamaki T, Okada Y, Uchiyama Y, et al. Synchronized 218(2):115124 [8] Alessandri G, Pagano S, Bez A, et al. Isolation and culture of vessels by murine skeletal muscle-derived CD34(-)/45(-) human muscle-derived stem cells able to differentiate into cells. Histochem Cell Biol. 2007; 128(4): 349-360. myogenic and neurogenic cell lineages. Lancet. 2004, 364 9448):1872-1883 /SSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH C1994-2013ChinaAcademicJournalElectronicPublishingHouse.Allrightsreservedhttp://www.cnki.net丁维进，等. 肌源干细胞在组织工程和再生医学的应用 ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH 4333 www.CRTER.org 是否能从人体组织中分离得到具有单一确切标记物 的肌源干细胞细胞群，如何调节体内微环境诱导肌源 干细胞定向分化，如何调控肌源干细胞与受区周围细 胞之间的相互作用，如何深入了解肌源干细胞移植后 与性别相关的差异表现，如何通过更为精准的基因学 方法调控肌源干细胞的命运，这些都是肌源干细胞研 究必须面临的问题。肌源干细胞诸多的优势已经表现 为其在组织工程学和再生医学研究和临床尝试治疗 方面的广泛应用，然而，最终将之安全有效的推广到 临床应用，有赖于以上问题的解决和肌源干细胞分化 调控机制的深度阐明。 作者贡献：第一、二作者进行实验实施，第三作者进 行实验评估，成文为第一作者，第三作者进行实验设计与 审校，第一作者对文章负责。 利益冲突：课题未涉及任何厂家及相关雇主或其他经 济组织直接或间接的经济或利益的赞助。 伦理要求：未涉及伦理问题。 作者声明：文章为原创作品，内容不涉及泄密，无一 稿两投，无抄袭，无内容剽窃，无作者署名争议，无与他 人课题以及专利技术的争执，内容真实，文责自负。 4 参考文献 [1] Katz B.The terminations of the afferent nerve fibre in the muscle spindles of the frog. Philos Trans R Soc Lond B Biol Sci. 1961;243:221-240. [2] Yu M, Zhang C, Zhang Y, et al. BM stem cell transplantation rescues pathophysiologic features of aged dystrophic mdx muscle. Cytotherapy. 2007;9(1):44-52. [3] Bhagavati S, Xu W. Isolation and enrichment of skeletal muscle progenitor cells from mouse bone marrow. Biochem Biophys Res Commun. 2004;318(1):119-124. [4] Seale P, Sabourin LA, Girgis-Gabardo A, et al. Pax7 is required for the specification of myogenic satellite cells. Cell. 2000;102(6):777-786. [5] Qu Z, Huard J. Matching host muscle and donor myoblasts for myosin heavy chain improves myoblast transfer therapy. Gene Ther. 2000;7(5):428-437. [6] Arsic N, Mamaeva D, Lamb NJ, et al. Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages. Exp Cell Res. 2008; 314(6):1266-1280. [7] Seale P, Rudnicki MA. A new look at the origin, function, and "stem-cell" status of muscle satellite cells. Dev Biol. 2000; 218(2):115-124. [8] Alessandri G, Pagano S, Bez A, et al. Isolation and culture of human muscle-derived stem cells able to differentiate into myogenic and neurogenic cell lineages. Lancet. 2004;364 (9448):1872-1883. [9] Qu-Petersen Z, Deasy B, Jankowski R, et al. Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. J Cell Biol. 2002;157(5):851-864. [10] Gallacher L, Murdoch B, Wu DM, et al. Isolation and characterization of human CD34(-)Lin(-) and CD34(+)Lin(-) hematopoietic stem cells using cell surface markers AC133 and CD7. Blood. 2000;95(9):2813-2820. [11] Oshima H, Payne TR, Urish KL, et al. Differential myocardial infarct repair with muscle stem cells compared to myoblasts. Mol Ther. 2005;12(6):1130-1141. [12] Claros S, Alonso M, Becerra J, et al. Selection and induction of rat skeletal muscle-derived cells to the chondro-osteogenic lineage. Cell Mol Biol (Noisy-le-grand). 2008;54(1):1-10. [13] Musgrave DS, Bosch P, Lee JY, et al. Ex vivo gene therapy to produce bone using different cell types. Clin Orthop Relat Res. 2000;(378):290-305. [14] Wright V, Peng H, Usas A, et al. BMP4-expressing muscle-derived stem cells differentiate into osteogenic lineage and improve bone healing in immunocompetent mice. Mol Ther. 2002;6(2):169-178. [15] Corsi KA, Pollett JB, Phillippi JA, et al. Osteogenic potential of postnatal skeletal muscle-derived stem cells is influenced by donor sex. J Bone Miner Res. 2007;22(10):1592-1602. [16] Peng H, Usas A, Gearhart B, et al. Development of a self-inactivating tet-on retroviral vector expressing bone morphogenetic protein 4 to achieve regulated bone formation. Mol Ther. 2004;9(6):885-894. [17] Lee JY, Musgrave D, Pelinkovic D, et al. Effect of bone morphogenetic protein-2-expressing muscle-derived cells on healing of critical-sized bone defects in mice. J Bone Joint Surg Am. 2001;83-A(7):1032-1039. [18] Adachi N, Sato K, Usas A, et al. Muscle derived, cell based ex vivo gene therapy for treatment of full thickness articular cartilage defects. J Rheumatol. 2002;29(9):1920-1930. [19] Kuroda R, Usas A, Kubo S, et al. Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells. Arthritis Rheum. 2006;54(2):433-442. [20] Lee JY, Cannon TW, Pruchnic R, et al. The effects of periurethral muscle-derived stem cell injection on leak point pressure in a rat model of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2003;14(1):31-37. [21] Huard J, Yokoyama T, Pruchnic R, et al. Muscle-derived cell-mediated ex vivo gene therapy for urological dysfunction. Gene Ther. 2002;9(23):1617-1626. [22] Proaño AR, Medrano A, Garrido G, et al. Muscle-derived stem cell therapy for stress urinary incontinence. Actas Urol Esp. 2010;34(1):15-23. [23] Vadalà G, Sobajima S, Lee JY, et al. In vitro interaction between muscle-derived stem cells and nucleus pulposus cells. Spine J. 2008;8(5):804-809. [24] Schultz SS, Lucas PA. Human stem cells isolated from adult skeletal muscle differentiate into neural phenotypes. J Neurosci Methods. 2006;152(1-2):144-155. [25] Tamaki T, Okada Y, Uchiyama Y, et al. Synchronized reconstitution of muscle fibers, peripheral nerves and blood vessels by murine skeletal muscle-derived CD34(-)/45 (-) cells. Histochem Cell Biol. 2007;128(4):349-360