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Fabrication of Myogenic Engineered Tissue Constructs
Published on: May 1, 2009
Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy
C Powell1, J Shansky, M Del Tatto
1Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912, USA.
Human Gene Therapy
|March 27, 1999
Summary
Human skeletal muscle stem cells can be genetically modified to create bioartificial muscles (BAMs) for therapeutic protein delivery. This research demonstrates the potential for autologous cell-based therapies using engineered muscle tissue.
Area of Science:
- Biotechnology
- Regenerative Medicine
- Gene Therapy
Background:
- Bioartificial muscles (BAMs) engineered from murine cells can deliver growth factors.
- Developing a human therapeutic cell-based protein delivery system is a key goal.
Purpose of the Study:
- To design genetic tissue-engineering techniques for human skeletal muscle stem cells.
- To evaluate the feasibility of using autologous human myoblasts for therapeutic protein secretion.
Main Methods:
- Isolated, cloned, and expanded human skeletal muscle stem cells from healthy and elderly patients.
- Transduced myoblasts ex vivo with retroviral vectors to secrete recombinant human growth hormone (rhGH).
- Engineered transduced myoblasts into human BAMs with differentiated myofibers.
Main Results:
- Cell yield, myoblast percentage, senescence, and doubling time were similar between healthy and elderly groups.
- Myoblasts from both groups were equally transduced to secrete 0.5-2 microg rhGH/10(6) cells/day.
- Human BAMs were successfully created containing postmitotic myofibers.
Conclusions:
- Autologous human skeletal myoblasts can be isolated and genetically modified.
- Engineered human myoblasts can form implantable living protein secretory devices.
- This approach holds promise for therapeutic protein delivery in humans.
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Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...

