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J Urol. 2013 Nov;190(5):1938-45. doi: 10.1016/j.juro.2013.04.052. Epub 2013 Apr 22.

Long-term structural and functional effects of autologous muscle precursor cell therapy in a nonhuman primate model of urinary sphincter deficiency.

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1
Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina.

Abstract

PURPOSE:

We measured the long-term efficacy of autologous muscle precursor cell therapy in premenopausal female nonhuman primates with sustained urinary sphincter deficiency.

MATERIALS AND METHODS:

Urinary sphincter deficiency was created in adult premenopausal female cynomolgus monkeys by selectively cauterizing and then transecting the pudendal innervation to the sphincter complex. The monkeys were then treated (18) or not treated (18) with intra-urinary sphincter injections of 5 million autologous green fluorescent protein labeled skeletal muscle precursor cells. Four untreated, uninjured monkeys served as controls. Maximal urethral pressure measurement and corresponding histological analysis of the structural and cellular components of the sphincter complex were performed up to 12 months after injection.

RESULTS:

Cell treatment produced sustained (12 months) increases in resting, somatic nerve stimulated and adrenergic nerve stimulated maximal urethral pressure, and a greater percent of sphincter area occupied by muscle as well as a decrease in the sphincter area occupied by collagen compared to the untreated group (each p>0.05). These results were within control values (each p>0.05). By 3 months after injection green fluorescent protein positive cells were found in the skeletal muscle layer, expressing desmin and connexin-43, and in the smooth muscle layer, expressing α-smooth muscle actin and connexin-43, and they were incorporated into the subendothelial vasculature, expressing Von Willebrand factor. Cell injected sphincter tissue contained a mixture of green fluorescent protein positive cells and predominantly green fluorescent protein negative cells.

CONCLUSIONS:

Injected skeletal muscle progenitor cells incorporated into the injured sphincter complex resulted in long-term structural and functional restoration of the injured sphincter complex in this nonhuman primate model.

KEYWORDS:

DMEM; Dulbecco's modified Eagle's medium; FACS; GFP; MHC; MPC; MUP; Macaca fascicularis; MyoD; PAX7; SUI; fluorescence antibody cell sorting; green fluorescent protein; maximal urethral pressure; muscle progenitor cell; myoblast determination protein; myosin heavy chain; paired box protein-7; pudendal nerve; skMPC; skeletal MPC; stem cells; stress; stress urinary incontinence; urinary bladder; urinary incontinence

PMID:
23618586
DOI:
10.1016/j.juro.2013.04.052
[Indexed for MEDLINE]
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