MR imaging relaxometry allows noninvasive characterization of in vivo differentiation of muscle precursor cells.

Abstract

To demonstrate the feasibility of in vivo monitoring of the myogenic differentiation process from human muscle precursor cells to mature skeletal muscle tissue by measuring characteristic magnetic resonance (MR) imaging relaxation and diffusion properties as a potential noninvasive diagnostic tool in muscle cell therapy. The study was approved by the ethics committee for studies in humans and the animal care committee. The hypothesis was tested by means of subcutaneous injection of human muscle precursor cells from the rectus abdominis muscle into nude mice (n = 18). Animals injected with human fibroblasts, prostate cancer cells, or collagen served as control animals (four in each group). T1, T2, T2*, and apparent diffusion coefficients (ADCs) were measured at 4.7-T MR imaging. MR imaging parameters were statistically evaluated by using analysis of variance with Bonferroni correction. The engineered muscle was characterized by means of immunofluorescence, Western blot, and contraction assays. Muscle tissue in the early stages of the differentiation process exhibited distinctly higher T1 (mean ± standard deviation, 2242 msec ± 116), T2 (224 msec ± 18), and T2* (33.3 msec ± 3.6) values and ADCs (1.53 × 10(-3) mm(2)/sec ± 0.03) compared with those of skeletal muscle. The muscle precursor cells exhibited a nonspecific pattern compared with that in control animals in the early stages. During differentiation, the relaxation and diffusion parameters decreased and approached the values for mature skeletal muscle tissue: T1, 1386 msec ± 88; T2, 32.0 msec ± 4.3; T2*, 10.8 msec ± 0.8; ADC, 1.39 × 10(-3) mm(2)/sec ± 0.02 (reference erector spinae muscle tissue: T1, 1417 msec ± 106; T2, 31.0 msec ± 2.4; T2*, 11.3 msec ± 1.7; and ADC, 1.40 × 10(-3) mm(2)/sec ± 0.03). MR imaging relaxation and diffusion measurements can be used as potential biomarkers for noninvasive in vivo monitoring of the myogenic differentiation process from muscle precursor cells to mature skeletal muscle tissue in muscle cell therapy.