Table 3.
Author | Journal | Year | Compartive/Non-Comparative | Cell Source | Subject Type; aGe at Treatment | Modified/Unmodified | Cell Harvesting and Processing | Injection Method | Number of Independent Measurements | Measurement Methodology * | Reference |
---|---|---|---|---|---|---|---|---|---|---|---|
Dai A. et al. (2018) [19] | Degenerative Neurological and Neuromuscular Disease | 2018 | Non-comparative | Human | Human; 7 to 14 years old | Unmodified | Umbilical cords were obtained from consenting patients delivering full-term infants by Caesarian section | 2 × 106 cells/kg/dose injections every 2 weeks for 4 months, alternating between systemic intra-arterial administration and local intramuscular injections | 5 | Electromyography; Spirometry; Echocardiography; Immunohistochemical analysis; Fluorescent in situ hybridization | [19] |
Siemionow M. et al. (2019) [20] | Stem Cell Reviews and Reports | 2019 | Comparative | mdx mice; snj (wild type) mice | Mdx mice; 8 weeks old | Modified | Myoblasts were harvested from the hind limb muscles of both wild type and mdx mice. MSCs were harvested from the femur and tibia of mdx mice only. The fusion cells MBwt/MBmdx and MBwt/MSCmdx were created. Some MBwt, MBmdx, and MSCmdx were saved | 60 μL systemic-intraosseous saline injections to femoral bone | 3 | Histological and immunofluorescence of cardiac muscle cross sections; Echocardiography Assessment | [20] |
Pang R. et al. (2014) [21] | Cytotherapy | 2014 | Comparative | Human | Mdx mice; 6 weeks old | Unmodified | To induce myogenic differentiation, cells were cultured in myogenic differentiation medium (Lonza, Basel, Switzerland) for 10 days. | Two million ELSCs or MSCs in 500 μL of saline were injected into each mouse through the tail vein. For control, 500 μL of saline was injected through the tail vein. | 9 | Analysis of motor function via traction, rotating rod, and running wheel tests; CK activity via NADPH fluorescence kit followed by spectrophotometry; Immunohistochemistry; Western blotting; RT-PCR; Histological analysis | [21] |
Valadares M. et al. (2014) [22] | Stem Cell Reviews and Reports | 2014 | Comparative | Human | Mdx mice; 7 weeks old | Unmodified | Four tissue specimens from a 46-year-old healthy female donor, namely: adipose tissue, muscle, fallopian tubes and endometrium were obtained from total hysterectomy procedures. All pericyte populations were confirmed to have at least 75 % purity after sorting. | Injected intraperitonially with 1 million viable cells (or vehicle), once a week, for a total of 8 weeks, without any immunosuppression. These seven groups were comprised by animals receiving either: vehicle, fibroblasts, myoblasts, pericytes (endometrium), pericytes (fallopian tubes), pericytes (adipose tissue) and pericytes (muscle). | 9 | Analysis of motor function via ambulation test, grip test, and rotarod; Myogenic differentiation; qPCR; PCR; Western blot; Immunohistochemistry; Histological analysis | [22] |
Esper G. et al. (2015) [23] | Evidence-Based Complementary and Alternative Medicine | 2015 | Comparative | Human | Mdx mice; 4 to 6 weeks old | Modified | MSCs derived from deciduous teeth were obtained using a modified Miura’s protocol with collagenase type I for pulp digestion | 1 × 104 cells suspended in 20 microliters saline injected every three weeks, totaling three injections via acupoint at Bladder 47, 49, and 52. | 3 | Analysis of motor function via wire test; CK-NAC; Histological analysis | [23] |
Siemionow M. et al. (2021) [24] | Stem Cells and Development | 2021 | Comparative | Human | Mdx mice; 6 to 8 weeks old | Modified | Allogenic human myoblasts and normal human bone marrow-derived MSCs underwent fusion exvivo using polyethylene. Cells presenting double PKH26/PKH67 staining were sorted through fluoresence-activated cell sorting and used for in vitro and invivo analysis | 0.25 × 106 fused cells or 0.5 × 106 of unfused cells were suspended in 60 microliters of Dulbecco’s phosphate-buffered saline. This volume was delivered into the left gastrocnemius of each mouse through six injections | 6 | Analysis of motor function via wire hanging and grip strength test, in situ muscle force test, and ex vivo muscle force test; Histological analysis; Immunofluoresence analysis | [24] |
Nitahara-Kashara et al. (2021) [25] | Stem Cell Research & Therapy | 2021 | Comparative | Sprague-Dawley rats, Human, Beagle dogs | NOD/SCID mice, Beagle dogs, Canine X-linked muscular dystrophy model (CXMDj); 3 to 52 months old | Modified | MSCs isolated from Sprague-Dalwey rat bone marrow were transduced with a luciferase-expressing retroviral vector. Canine CD271 + MSCs were also transduced with a luciferase-expressing retroviral vector as well as an enhnaced green fluorescent protein (eGFP) or MyoD-expressing adenoviral vector. MSCs or human dental pulp stem cells (hDPSCs) were transduced with adeno-associated virus (AAV)/eGFP or control AAV1/IL-10 vectors | 5.0–10.0 × 106 luciferase-expressing rat MSCs were injected intramuscularly into the right or lift hindlimb muscle of NOD/SCID mice pretreated with cardiotoxin 1 day before treatment. 1.0 × 107 of both eGFP-MSCs and IL-10-MSCs were injected into the right and left hindlimb, respectively. AAV1/IL-10 transduced Luc-CD271 + MSCs (2.4–2.7 × 107 cells/2 mL) were injected into the muscles of healthy beagles on days 0 and 50 without immunosupressants. The tibialis anterior muscles were pretreated by injecting 10 nmol/kg of cardiotoxin. hDPSCs or AAV1/IL-10 transduced hDPSCs (4.0 × 106 cells/mL/kg body weight at a rate of 1 mL/min) was adminstered intravenously into CXMDj using nine injections at two week intervals. | 13 | Analysis of motor function via 15-m running time and counts of spontaneous locomotor activity; Creatinine kinase; Alanine aminotransferase; Aspartate aminotransferase; blood urea nitrogen; Histological analysis; Immunohistochemical analysis; ELISA; Luciferase reporter assays; Biodistribution of MSCs; Cytokine/cytokine array; MRI | [25] |
Geng J et al. (2009) [26] | Cytotherapy | 2009 | Comparative | Sprague-Dawley rats | Mdx mice; 7 to 9 weeks old | Modified | Femur and tibia bone marrow mesenchymal stem cells were incubated in complete medium containing 10 μM 5-AzaC for 24 h to induce differentiation, and incubated with or without 10–100 μg/mL polyclonal anti-myostatin Ab in differentiation medium | 1.2 × 107 MSC of the mixture were infused per mouse through the tail vein. One day before transplantation, mdx mice in the Ab transplantation group were injected intraperitoneally with anti-myostatin antibody (6 mg/kg/week). | 5 | Immunofluorescence analysis; RT-PCR; Motor function via Rota-rod; CK-NAC; Western blot | [26] |
Li Z. et al. (2011) [27] | Cytotherapy | 2011 | Comparative | Sprague-Dawley rats | Mdx mice; 6 weeks old | Unmodified | Bone marrow MSCs were extracted from the femurs and tibias of male rats. | Cell density was adjusted to 1 × 107/mL. A volume of 0.5 mL MSC suspended in PBS was administered via tail vein injection into each experimental dko mouse, and matched controls were administered equivalent injections of PBS. | 5 | Analysis of motor function via traction, rotating rod, and running wheel tests; Histological analysis; Detection of grafted cells | [27] |
Ruehle M. et al. (2018) [28] | Journal of Tissue Engineering and Regenerative Medicine | 2018 | Comparative | Wild type C57BL/6 mice | Mdx mice; 12 weeks old | Modified | Mesenchymal stem cells were lentivirally GFP-labelled to confirm multipotency and proliferative capacity. Some cells were formed into aggregates by centrifuging and incubating overnight to form spheroidal aggregates | Mice received local 100 μL injections containing MSC aggregates, MSC single cells, or saline. 5 × 105 MSCs were in each injection except for saline | 4 | Peak isometric torque via servomotor and Pt-Ir needle electrodes; Histological analysis; Cell immunomodulatory factor quantification | [28] |
Rousseau J. et al. (2010) [29] | Cell Transplantation | 2010 | Comparative | Normal C57BL/10 J and C57BL/10 J mdx/mdx mice | Mdx mice; 12 month old | Unmodified | Muscles dissected from arms and legs were cut into small fragments and digested with collagenase and dispase. After 48 hrs in culture, Muscle precursor cells were frozen in nitrogen until transplantation. | A total of 1.5 million cells were injected in several sites throughout each of the left and right extensor digitorum longus | 2 | Analysis of motor function via electrode stimulation in organ bath; Immunohistochemistry | [29] |
* Measurement methodologies considered to directly measure muscle function are bolded.