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DOI: 10.1055/s-2000-10168
Georg Thieme Verlag Stuttgart · New York
Tissue Engineering und Gentherapie des Bewegungsapparates mit Muskelzellen
Muscle-Base Tissue Engineering and Gene Therapy of the Musculoskeletal System.Publikationsverlauf
Publikationsdatum:
31. Dezember 2000 (online)
![](https://www.thieme-connect.de/media/zfo/200005/lookinside/thumbnails/10.1055-s-2000-10168-1.jpg)
Zusammenfassung.
Ziel: Der Einsatz von Muskelgewebe in der somatischen Gentherapie ermöglicht den Transfer von Genen in betimmte Gewebe mit einer biochemischen Funktionsstörung. Methode: Muskelgewebe ist im Einsatz der Gentherapie und im Tissue Engineering vielversprechend. Viele Muskelgruppen sind per injectionem direkt erreichbar und können wiederholt biopsiert und in relativ großen Mengen gewonnen werden, ohne die Gesundheit des Patienten zu beeinträchtigen. Muskelgewebe besteht aus vielkernigen, postmitotischen Muskelfasern, welche eine hohe und langfristige transgene Expression ermöglichen. Letztendlich ist Muskelgewebe gut vaskularisiert, was über die Blutbahn eine systemische Wirksamkeit erzielen lässt. Ergebnisse: Zellen muskulären Ursprungs können die Muskelheilung und Knochenheilung fördern. Transplantierte Zellen muskulären Ursprungs ermöglichen eine lang anhaltende Expression von therapeutischen Proteinen. Die aus der Muskulatur isolierten Stammzellen sind pluripotent und können u. a. in Osteoblasten differenzieren. Schlussfolgerung: Diese Charakeristika voraussetzend sind im Folgenden vier Anwendungsmöglichkeiten des Tissue Engineerings und der Gentherapie mit Muskelgewebe beschrieben: Erbliche Muskelerkrankungen, Muskelverletzungen und Rekonstruktion, Knochenheilung und intraartikuläre Läsionen.
Aim: Muscle-based somatic gene therapy is a novel way to alleviate a biochemical deficiency. Method: Muscle-derived cells are very promising in the field of gene therapy and tissue engineering. First, most muscle tissue is accessible by injection. Second, muscle tissue consists of multinucleated, postmitotic myofibers, which enable a long-term expression of the transduced gene. Third, muscle tissue can be biopsied easily. It is available in abundance and the biopsy does not compromise the health and function of the patient. Finally, muscle tissue is highly vascularized, which makes systemic delivery feasible. Results: Muscle-derived cells can promote muscle healing and bone healing. Implanted cells maintain a long-term transgene expression of therapeutic proteins. Isolated, muscle-derived stem cells can differentiate in osteoblasts. Conclusion: Based on these characteristics, we present four possible applications: inherited muscular diseases, muscle injury, bone healing, and intraarticular disorders.
Schlüsselwörter:
Gentherapie - Stammzellen - Muskelverletzung - Knochenheilung - Arthrose
Key words:
Gene therapy - stem cell - muscle injury - bone healing - arthritis
Literatur
- 01 Arahata K, Ishiura S, Ishiguro T, Tsukahara T, Suhara Y, Eguchi C, Ishihara T, Nonaka I, Ozawa E, Sugita H. Immunostaining of skeletal and cardiac muscle surface membrane with antibody against Duchenne muscular dystrophy peptide. Nature. 1988; 333 861-863
- 02 Arnoczky S P, Tarvin G B, Marshall J L. Anterior cruciate ligament replacement using patellar tendon. An evaluation of graft revascularization in the dog. J Bone Joint Surg [Am]. 1982; 64 217-224
- 03 Bandara G, Mueller G M, Galea-Lauri J, Tindal M H, Georgescu H I, Suchanek M K, Hung G L, Glorioso J C, Robbins P D, Evans C H. Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer. Proc Natl Acad Sci USA. 1993; 90 10764-10768
- 04 Bonilla E, Samitt C E, Miranda A F, Hays A P, Salviati G, DiMauro S, Kunkel L M, Hoffman E P, Rowland L P. Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell. 1988; 54 447-452
- 05 Bosch P, Musgrave D S, Shuler F, Ghivizzani S C, Evans C, Robbins P D, Huard J. Bone formation by muscle derived stem cells. Nat Biotech 1999 (GENERIC) Ref Type: Generic
- 06 Caplan A I. Mesenchymal stem cells. J Orthop Res. 1991; 9 641-650
- 07 Conti N A, Dai Y. The effects of exogenous growth factors on the healing of ligaments. Transplant Proc 18, 60. 1993. (GENERIC) Ref Type: Generic.
- 08 Day C S, Kasemkijwattana C, Menetrey J, Floyd S SJ, Booth D, Moreland M S, Fu F H, Huard J. Myoblast-mediated gene transfer to the joint. J Orthop Res. 1997; 15 894-903
- 09 Dhawan J, Pan L C, Pavlath G K, Travis M A, Lanctot A M, Blau H M. Systemic delivery of human growth hormone by injection of genetically engineered myoblasts [see comments]. Science. 1991; 254 1509-1512
- 10 Garrett W EJ, Safran M R, Seaber A V, Glisson R R, Ribbeck B M. Biomechanical comparison of stimulated and nonstimulated skeletal muscle pulled to failure. Am J Sports Med. 1987; 15 448-454
- 11 Hildebrand K A, Woo S L, Smith D W, Allen C R, Deie M, Taylor B J, Schmidt C C. The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament. An in vivo study. Am J Sports Med. 1998; 26 549-554
- 12 Huard J, Roy R, Guerette B, Verreault S, Tremblay G, Tremblay J P. Human myoblast transplantation in immunodeficient and immunosuppressed mice: evidence of rejection. Muscle Nerve. 1994; 17 224-234
- 13 Hurme T, Kalimo H. Activation of myogenic precursor cells after muscle injury. Med Sci Sports Exerc. 1992; 24 197-205
- 14 Jarvinen M. Healing of a crush injury in rat striated muscle. 4. Effect of early mobilization and immobilization on the tensile properties of gastrocnemius muscle. Acta Chir Scand. 1976; 142 47-56
- 15 Jiao S, Gurevich V, Wolff J A. Long-term correction of rat model of Parkinson's disease by gene therapy [retraction of Jiao S, Gurevich V, Wolff JA. In: Nature 1993 Apr 1; 362 (6419): 450 - 3]. Nature. 1996; 380 734
- 16 Kasemkijwattana C, Menetrey J, Somogyl G, Moreland M S, Fu F H, Buranapanitkit B, Watkins S C, Huard J. Development of approaches to improve the healing following muscle contusion. Cell Transplant. 1998; 7 585-598
- 17 Kawasaki K, Aihara M, Honmo J, Sakurai S, Fujimaki Y, Sakamoto K, Fujimaki E, Wozney J M, Yamaguchi A. Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin. Bone. 1998; 23 223-231
- 18 Lau H T, Yu M, Fontana A, Stoeckert C JJ. Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice [see comments]. Science. 1996; 273 109-112
- 19 Lynch C M, Clowes M M, Osborne W R, Clowes A W, Miller A D. Long-term expression of human adenosine deaminase in vascular smooth muscle cells of rats: a model for gene therapy. Proc Natl Acad Sci USA. 1992; 89 1138-1142
- 20 Menetrey J, Kasemkijwattana C, Fu F H, Moreland M S, Huard J. Suturing versus immobilization of a muscle laceration. A morphological and functional study in a mouse model. Am J Sports Med. 1999; 27 222-229
- 21 Pruchnic R, Cao B H, Qu Z, Xiao X, Li J, Samulski R J, Epperly M, Huard J. The use of adeno-associated virus to circumvent the maturation dependent viral transduction of muscle fibers. accepted in Hum Gen Th. 1999. (GENERIC) Ref Type: Generic.
- 22 Qu Z, Balkir L, van Deutekom J C, Robbins P D, Pruchnic R, Huard J. Development of approaches to improve cell survival in myoblast transfer therapy. J Cell Biol. 1998; 142 1257-1267
- 23 Robbins P D, Evans C H, Chernajovsky Y. Gene therapy for rheumatoid arthritis. Springer Semin Immunopathol. 1998; 20 197-209
- 24 Schultz E. Satellite cell behavior during skeletal muscle growth and regeneration. Med Sci Sports Exerc. 1989; 21 S181-S186
- 25 Schultz E, Jaryszak D L, Valliere C R. Response of satellite cells to focal skeletal muscle injury. Muscle Nerve. 1985; 8 217-222
- 26 Seale P, Rudnicki M A. A new look at the origin, function, and „Stem-Cell” status of muscle satellite cells [In Process Citation]. Dev Biol. 2000; 218 115-124
- 27 Simonson G D, Groskreutz D J, Gorman C M, MacDonald M J. Synthesis and processing of genetically modified human proinsulin by rat myoblast primary cultures. Hum Gene Ther. 1996; 7 71-78
- 28 Urist M R. Bone: formation by autoinduction. Science. 1965; 150 893-899
- 29 Young H E, Mancini M L, Wright R P, Smith J C, Black A CJ, Reagan C R, Lucas P A. Mesenchymal stem cells reside within the connective tissues of many organs. Dev Dyn. 1995; 202 137-144
- 30 Zubrzycka-Gaarn E E, Bulman D E, Karpati G, Burghes A H, Belfall B, Klamut H J, Talbot J, Hodges R S, Ray P N, Worton R G. The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle. Nature. 1988; 333 466-469
Professor J. HuardPh. D. Assistant Professor
Growth and Development LaboratoryDepartment of Orthopaedic Surgery and Molecular Genetics and BiochemistryChildren's Hospital of Pittsburgh and University of Pittsburgh
Pittsburgh, PA 15213
USA
Telefon: Tel. (4 12) 6 92-78 07
Fax: Fax (4 12) 6 92-70 95
eMail: E-mail: jhuard+@pitt.edu