Systemic delivery of human bone marrow embryonic-like stem cells improves motor function of severely affected dystrophin/utrophin–deficient mice

The Efficacy of Naïve versus Modified Mesenchymal Stem Cells in Improving Muscle Function in Duchenne Muscular Dystrophy: A Systematic Review

“…Only one was non-comparative and was also the only study done on human patients with Duchenne Muscular Dystrophy (Dai et al [ 19 ]). Nine of the studies experimented on x-linked muscular dystrophy (mdx) mice, which are considered equivalent to Duchenne muscular dystrophy, with six using MSCs from humans (Siemionow M et al (2019) [ 20 ], Pang et al [ 21 ], Valadares et al [ 22 ], Esper et al [ 23 ], Siemionow M et al (2021) [ 24 ], and Nitahara-Kashara et al [ 25 ]), three using cells from Sprague-Dawley rats (Geng et al [ 26 ], Li et al [ 27 ], and Nitahara-Kashara et al [ 25 ]), and three studies using cells from utrophin/dystrophin double knockout (dko) mice. Mdx are the most widely used animal model for DMD research overall.…”

“…Two studies investigated cardiac function using echocardiography and/or electromyography (Dai et al [ 19 ], Siemionov et al (2019) [ 20 ]), and one study investigated respiratory function using spirometry (Dai et al). Four studies investigated muscle function using the rotarod performance test as a method (Pang et al [ 21 ], Valadares et al [ 22 ], Geng et al [ 26 ], Li et al [ 27 ]), three studies used electrodes to measure muscle function (Siemionov et al (2021) [ 24 ], Ruehle et al [ 28 ], Rousseau et al [ 29 ]), and two studies used a wire test to measure motor function (Esper et al [ 23 ], Siemionov et al (2021) [ 24 ]). All of the studies also measured other surrogates in conjunction with immunohistochemical and/or histological analysis to confirm muscle function.…”

“…A volume of 0.5 mL MSCs suspended in PBS was administered via tail vein injection into each experimental utrophin/dystrophin-deficient double knockout mouse, and matched controls were administered equivalent injections of PBS. Pang et al [ 21 ] induced the myogenic differentiation of embryonic-like stem cells (ELSCs) and MSCs by culturing them in myogenic differentiation medium (Lonza Group, Basel, Switzerland) for 10 days. Then, 2 × 10 6 ELSCs or MSCs in 500 μL of saline were injected into each mouse through the tail vein.…”

“…Li et al compared rat MSC transplantation into double knockout (dko) mice to wild type mice with PBS injections and dko mice with only PBS injections (no MSCs). Pang et al [ 21 ] performed embryonic stem cell and MSC injection into dko with saline injection only in dko mice as a control. Valadares et al [ 22 ] injected a variety of cell types (fibroblast, myoblast, endometrial pericyte, fallopian tube pericyte, adipose pericyte, and adipose pericyte) into dko mice and used vehicle (HBSS) injection only in dko mice as a control.…”

“…Siemionow et al’s (2019)* [ 20 ] study was the only one to measure cardiac function using echocardiography, and it found significant improvements in ejection fraction and fractional shortening. The remaining seven studies (Pang et al [ 21 ], Esper et al* [ 23 ], Siemionow et al (2021)* [ 24 ], Nitahara-Kashara et al* [ 25 ], Geng et al* [ 26 ], Ruehle et al* [ 28 ], Rousseau et al [ 29 ]) only measured limb function, and all of them were able to find improvements.…”