Background/Purpose: Sporadic inclusion body myositis (sIBM) is clinically characterised by marked progressive muscle weakness and impaired physical function. Physical training has become an area of interest with the aim of mitigating or circumventing the progressive decline in functional capacity, as immunosuppressive medication has shown little effect in sIBM patients. Low-load blood flow restricted (BFR) exercise has been shown to upregulate skeletal muscle stem cells (satellite cells) and evoke gains in myofiber cross sectional area. In addition, satellite cells appear to play an important role supporting myofiber hypertrophy through myonuclei addition and myofiber regeneration.

Consequently, the present study aimed to investigate the effect of BFR strength training on satellite cell content, myofiber hypertrophy and myogenic signalling markers in lower limb skeletal muscle of sIBM patients.

Methods: Muscle biopsies from a previous randomised control trial (NCT02317094) in sIBM patients performing 12-weeks of low-load blood flow restricted exercise were used. 11 patients (age: 67.5 + 6.5, months from diagnosis: 57.8 + 87.7) were included from the exercise group (BFRE) and 10 patients (age: 69.2 + 4.6, months from diagnosis: 46.6 + 27.2) from the control group (CON). Muscle biopsies were obtained from either the m. tibialis anterior or the m. vastus lateralis and were stained for Pax7, CD31, SIX1, KI67 and DAPI, which were visualized by using three-color immunofluorescence microscopy. Visiopharm-based image analysis quantification was used for assessing the amount of Pax7, CD31, SIX1, KI67 and DAPI positive cells. Myofiber cross sectional area was assessed in a separate analysis. A linear mixed model was used for the statistical analysis.

Results: Satellite cells (Pax7⁺) including newly proliferated satellite cells (Ki67⁺/Pax7⁺) remained unaltered following the intervention period in both BFRE and CON. Likewise, total myonuclei content (SIX1⁺DAPI⁺) and capillaries (CD31⁺) did not change in BFRE or CON. A group (intervention) by time interaction was observed in type 2 fibre cross-sectional area (CSA) (p=0.04).  Notably, type 1 fibres demonstrated a larger CSA than type 2 fibres both pre and post intervention and irrespective of group (p≤0.05).

Conclusion: 12 weeks of low-load blood flow restricted exercise training did not upregulate satellite cells, myogenic markers nor increase myofiber area in the present group of sIBM patients. These findings suggest that satellite cell function and myogenic capacity are impaired in long-term sIBM.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-blood-flow-restricted-strength-training-on-myogenic-stem-cells-and-myofiber-hypertrophy-in-sporadic-inclusion-body-myositis-patients/