Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation

Gussoni, Emanuela; Pavlath, Grace K.; Lanctot, Amy; Sharma, Khema R.; Miller, Robert G.; Steinman, Lawrence; Blau, Helen M.

doi:10.1038/356435a0

Cited by 398 publications

(188 citation statements)

References 25 publications

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“…14,15 Despite positive results in these small rodents, [16][17][18][19][20] clinical trials have presented limited success. [21][22][23][24][25][26][27][28][29] Improvements of injection and immunosuppression parameters have recently been achieved in primates 9,10,30 and translated to the human situation with encouraging, although localized success. 31 Nevertheless, one of the most important problems of heterologous MT remains the immune response raised by the recipient against donor cells.…”

Section: Introductionmentioning

confidence: 99%

Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients

Vilquin

Sacconi

et al. 2005

Gene Ther

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Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by a typical regional distribution, featuring composed patterns of clinically affected and unaffected muscles. No treatment is available for this condition, in which the pathophysiological mechanism is still unknown. Autologous transfer of myoblasts from unaffected to affected territories could be considered as a potential strategy to delay or stop muscle degeneration. To evaluate the feasibility of this concept, we explored and compared the growth and differentiation characteristics of myoblasts prepared from phenotypically unaffected muscles of five FSHD patients and 10 control donors. According to a clinically approved procedure, 10 9 cells of a high degree of purity were obtained within 16-23 days. More than 80% of these cells were myoblasts, as demonstrated by labeling of the muscle markers CD56 and desmin. FSHD myoblasts presented a doubling time equivalent to that of control cells; they kept high proliferation ability and did not show early telomere shortening. In vitro, these cells were able to differentiate and to express muscle-specific antigens. In vivo, they participated to muscle structures when injected into immunodeficient mice. These data suggest that myoblasts expanded from unaffected FSHD muscles may be suitable tools in view of autologous cell transplantation clinical trials.

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Section: Introductionmentioning

confidence: 99%

Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients

Vilquin

Sacconi

et al. 2005

Gene Ther

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“…This treatment regime, referred to as myoblast transfer therapy (MTT), depends upon: (i) the survival of cultured donor myoblasts; (ii) their migration away from the injection site; (iii) their fusion with one another, or host myofibers to form do nor-host hybrid fibers; and (iv) the ability of these hy brid myofibers to express normal dystrophin. MTT has been largely unsuccessful in both experimental and clin ical trials because most cultured donor myoblasts die soon after injection into host muscle (6,14,28,29,(33)(34)(35)37,39,43,44,66). This is the case even when fully histocompatible donor-host combinations are used (14,34).…”

Section: Introductionmentioning

confidence: 99%

Exposure to Tissue Culture Conditions Can Adversely Affect Myoblast Behavior in Vivo in Whole Muscle Grafts: Implications for Myoblast Transfer Therapy

Smythe

Grounds

2000

Cell Transplant

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The effects of tissue culture conditions on the viability of myoblasts in whole muscles transplanted in vivo were investigated. Whole male (SJL/J) donor muscles were exposed to various tissue culture reagents and proteolytic enzymes, and allografted into female (SJL/J) host mice. Desmin immunohistochemistry was used to assess the numbers of myogenic cells (as an index of myoblast viability and the extent of regeneration) in tissue sections of whole-muscle grafts sampled on days 7 and 14. DNA quantitation with a Y-chromosome-specific probe was used to determine the total Y-l sequence DNA (as an index of myoblast survival and proliferation) in whole-muscle grafts sampled on days 1, 3, and 7. In grafts exposed to serum-free medium, there was a delay in myoblast fusion at 7 days that was recovered by 14 days, but exposure to serum (10% or 20%) had a prolonged adverse effect on myotube formation at 14 days. DNA quantitation demonstrated that either serum-free culture medium or 10% serum enhanced the number of male cells within whole-muscle grafts at 7 days. Proteolytic digestion (even for 5 min) of whole muscles prior to grafting was extremely detrimental to myoblast survival and viability at 7 and 14 days. The unexpected finding of adverse effects of tissue culture conditions on the regeneration of whole-muscle grafts in vivo appears to parallel the major problem of the rapid death of isolated cultured donor myoblasts after injection in myoblast transfer therapy. The use of whole-muscle grafts provides an alternative and sensitive model to analyze the crucial effects of various tissue culture components on the subsequent survival and proliferation of myogenic cells in vivo.

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“…The first stem cell transplant into a DMD patient was performed in 1990 using myoblasts and held great promise for this type of treatment due to the apparent safety of the procedure, and the production of dystrophin (the affected protein in DMD) following transplantation [39]. However, in subsequent clinical trials, the results were inconsistent, with some, but not all, reporting dystrophin production and no significant clinical benefits [50,51].…”

Section: Myopathiesmentioning

confidence: 99%

Augmentation of Musculoskeletal Regeneration: Role for Pluripotent Stem Cells

2018

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The rise in the incidence of musculoskeletal diseases is attributed to an increasing ageing population. The debilitating effects of musculoskeletal diseases, coupled with a lack of effective therapies, contribute to huge financial strains on healthcare systems. The focus of regenerative medicine has shifted to pluripotent stem cells (PSCs), namely, human embryonic stem cells and human-induced PSCs, due to the limited success of adult stem cell-based interventions. PSCs constitute a valuable cell source for musculoskeletal regeneration due to their capacity for unlimited self-renewal, ability to differentiate into all cell lineages of the three germ layers and perceived immunoprivileged characteristics. This review summarizes methods for chondrogenic, osteogenic, myogenic and adipogenic differentiation of PSCs and their potential for therapeutic applications.

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Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation

Cited by 398 publications

References 25 publications

Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients

Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients

Exposure to Tissue Culture Conditions Can Adversely Affect Myoblast Behavior in Vivo in Whole Muscle Grafts: Implications for Myoblast Transfer Therapy

Augmentation of Musculoskeletal Regeneration: Role for Pluripotent Stem Cells

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