eISSN: 1897-4295
ISSN: 1734-9338
Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej
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4/2022
vol. 18
 
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abstract:
Original paper

Intraosseous transplant of dystrophin expressing chimeric (DEC) cells improves skeletal muscle function in mdx mouse model of Duchenne muscular dystrophy

Mohammad Malik
1
,
Maria Siemionow
1
,
Joanna Cwykiel
1
,
Ahlke Heydemann
2
,
Jesus Garcia-Martinez
3
,
Krzysztof Siemionow
1
,
Erzsebet Szilagyi
1

  1. Department of Orthopedics, University of Illinois at Chicago, Chicago, IL, USA
  2. Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA
  3. Department of Clinical Health Sciences, Saint Louis University, Saint Louis, MO, USA
Adv Interv Cardiol 2022; 18, 4 (70): 399–406
DOI: https://doi.org/10.5114/aic.2021.110990
Online publish date: 2021/11/20
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Introduction:
We previously reported that systemic delivery of dystrophin expressing chimeric (DEC) cells of normal (wt) and dystrophin-deficient (mdx) myoblast (MB) or mesenchymal stem cell (MSC) origin restored dystrophin expression and improved cardiac function in the mdx mouse model of Duchenne muscular dystrophy (DMD).

Aim: This study evaluated the effect of intraosseous delivery of murine DEC lines of MB (MBwt/MBmdx) and MSC (MBwt/MSCmdx) origin on function of gastrocnemius muscle (GM).

Material and methods:
DEC lines created by ex vivo fusion were tested in the mdx mouse model of DMD: Group 1 – vehicle (control), Group 2 – non-fused 0.25 × 106 MBwt and 0.25 × 106 MSCmdx (control), Group 3 – fused 0.5 × 106 MBwt/MBmdx DEC and Group 4 – fused 0.5 × 106 MBwt/MSCmdx DEC. In situ and in vitro muscle force tests assessed GM function at 90 days post-transplant.

Results:
Application of MBwt/MSCmdx and MBwt/MBmdx DEC significantly improved the fatigue ratio of GM compared to vehicle-injected controls detected by in vivo muscle force tests (0.567 ±0.116, p = 0.045 and 0.489 ±0.087, p < 0.05, respectively). MBwt/MSCmdx DEC recipients presented enhanced maximum force at tetanus (0.145 ±0.040 g/mg, p < 0.05); furthermore, recipients of MBwt/MBmdx DEC showed a significant increase in the maximum force generation rate compared to vehicle controls (4.447 ±1.090 g/s/mg, p < 0.05). The ex vivo GM force testing in MBwt/MSCmdx DEC recipients detected increased average GM force compared to vehicle and non-fused controls.

Conclusions:
Systemic-intraosseous administration of MBwt/MBmdx and MBwt/MSCmdx DEC therapy combining the myogenic and immunomodulatory properties of MB and MSC significantly improved skeletal muscle (GM) function of force and resistance to fatigue in an mdx mouse model of DMD.

keywords:

dystrophin expressing chimeric cells, DEC therapy, Duchenne muscular dystrophy, cell fusion, mesenchymal stem cells, myoblast
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