Table 4.

Experimental variables, results, and conclusions of selected studies.

Study	Variables	Controls	Modified/Unmodified	Effects on Muscle	Conclusions
Siemionow M. et al. (2019) [20]	MBwt + MBmdx	Wild type with no treatment	Modified	Increased ejection fraction and fractional shortening in MBwt/MBmdx and MBwt/MSCmdx compared to saline injected mdx controls	Fused cells are more efficacious in countering the effects of systolic dysfunction due to better engraftment potential and lower levels of rejection.
	MBwt + MSCmdx	Mdx mice with saline injection only		Increased ejection fraction and fractional shortening in MBwt/MBmdx and MBwt/MSCmdx compared to not-fused cells	MSCs are effective at maintaining cardiac function
	MBwt/MBmdx			MBwt/MBmdx and MBwt/MSCmdx mice had ejection values 10% and 20% higher, respectively, compared to vehicle injected controls
	MBwt/MSCmdx
Dai A. et al. (2018) [19]	Human wharton jelly-derived mesenchymal stem cells	None	Unmodified	Increased FVC and FEV1 for all patients	Positive effect for vital functions
				Increased or equal ejection fraction for 8 out of 9 patients	Questionable benefits in terms motility despite drop in CK
				No statistically significant difference between pre and post measure of muscle strength
				Significant difference between pre and posttreatment EMG measurement of amplitude in right and left suralis
Ruehle M. et al. (2018) [28]	Wild-type mice with myotoxic injury injected with single cell MSCs	Wild-type mice with myotoxic injury with saline only injections	Modified	No difference in peak isometric torque of the ankle plantar flexor muscles prior to treatment	Single cell MSCs are not effective at improving muscle function
	Wild-type mice with myotoxic injury injected with aggregated MSC	Mdx mice with no myotoxic injury with saline only injections		Aggregate treated mice had significantly greater torque than saline for both types of mice	Aggregated MSCs are effective at improving muscle function
	Mdx mice with no myotoxic injury injected with single MSCs			Aggregate MSCs had greater peak isometric torque compared to single cell for both types of mice	Aggregated MSCs may have avoided rapid clearance from tissue and remained within muscle longer than single cells, as aggregates could be identified for up to 7 days in the cardiotoxin-injured wild-type mice and for up to 3 days in the dystrophic tissue, whereas single cells could not be reliably identified by histology at any time point
	Mdx mice with no myotoxic injury injected with aggregated MSCs			Single cell MSCs had the same peak isometric torque as saline	Wild-type mice with myotoxic injury and mdx mice do not have a significant impact on the efficacy of stem cells
Geng J et al. (2009) [26]	Rat bone marrow mesenchymal stem cells (transplant)	No transplant	Modified	No difference between the no transplant and transplant group	MSCs alone are ineffective at improving muscle function
	Rat bone marrow mesenchymal stem cells + myostatin antibody (Ab transplant)			Ab transplant group greatly improved motor function compared to no transplant and transplant	Inhibition of myostatin improves the MSC ability to improve muscle function
Li Z. et al. (2011) [27]	MSC transplantation	PBS injection only wild type	Unmodified	Until 15 weeks after transplantation, no abnormalities were observed in either the diet or behavior of transplanted mice	MSCs provide significant improvements in motor function and lifespan, although it is still significantly worse than normal mice
		PBS injection only dko mice		The median lifespan of normal control mice was significantly higher than both other groups, but the median lifespan of the transplantation group (35 wks) was significantly higher than that of the control mice (22 wks)
				All motor function tests showed significant improvement in experimental mice compared to control groups. Normal control mice performed significantly better than experimental mice, though
Pang R. et al. (2014) [21]	ELSC injection	Saline injection only dko mice	Unmodified	ELSC transplanted mice had significantly improved motor function in all tests compared with dko mice transplanted with MSCs or saline	ELSCs were superior to MSCs by every metric, even though MSCs were already significantly better than saline only injections. The increased myogenic differentiation of ELSCs may be responsible for this discrepancy
	MSC injection
Valadares M. et al. (2014) [22]	Fibroblast injection	Vehicle (HBSS) injection only in dko mice	Unmodified	Endometrial-derived pericytes showed significant effects related to the age of the onset of injections. The younger the dko mice started being treated, the better the survival. This observation was not seen in any other treated groups	All cells were ineffective at engrafting and providing significant benefits to muscle function
	Myoblast injection			Only adipose derived pericytes increased life expectancy in mdx mice
	Endometrial pericyte injection			Despite improved survival in adipose pericyte injected mice, none of the physical tests revealed differences between the groups
	Fallopian tube pericyte injection			No human cells were found in any analyzed tissues and no difference in the HE stained sections of the gastrocnemius muscle
	Adipose pericyte injection			No in vitro myogenic potential in pericytes derived from any tissue source was found
	Muscle pericyte injection
Esper G. et al. (2015) [23]	False aquapuncture with SHEDs	No aquapuncture	Modified	Strength improvement in mice with SHED/true acupoints and only slight improvement with saline/true acupoints and SHED/false acupoints compared to controls	Acupuncture and MSCs each have a beneficial effect in muscle force that can complement each other
	True aquapuncture with saline			Although creatine kinase decreased in all treatments, only SHED/true acupoint was able to improve force
	True aquapuncture with SHEDs
Rousseau J. et al. (2010) [29]	Mdx mice transplanted with 10 J MPCs	No treatment mdx mice	Unmodified	There was no significant force difference observed between the different groups, even those injected with cardiotoxin	Replacing dystrophin can increase resistance to exercise and contraction-induced injury but not sufficiently enoigh to increase the strength of the muscle
	Mdx mice transplanted with mdx MPCs	Mdx mice injected with cardiotoxin only		Mdx mice with 10 J MPCs transplanted increased muscle protection against eccentric contractions
Siemionow M. et al. (2021) [24]	MB/MSC fused cells	DPBS injection only	Modified	MB/MSC fused cells significantly improved in vivo muscle force and reduced fibrosis compared with vehicle-injected controls and non fused MB and MSC cells	Fused cells were more effective at improving muscle function than unfused cells
	Not-fused MB and MSC
Nitahara-Kashara et al. (2021) [25]	Mice transplanted with IL-10 MSCs	Mice transplanted with GFP-MSCs	Modified	Muscle function was not measured specifically in mice, but IL-10 expressing MSCs had significantly more cell survival and were more effective at enhancing post-transplantation retention. Il-10-Luc-MSCs were retained for more than 67 days after transplantation	Higher retention in early stages exerts a significant effect on long-term engraftment
	Beagles transplanted with cardiotoxin and IL-10-Luc-CD271 + MSCs	Beagles transplanted with cardiotoxin and MyoD-Luc-CD271 + MSCs		Lucisferase activity, which correlates to the number of MSCs, tended to be higher in IL-10-Luc-CD271 + MSCs. IL-10 levels in IL-10-Luc-CD271+ MSC treated tibialis anterior muscles increased, while those in MYoD-Luc-CD271 +MSC-treated muscles did not.	IL-10 expressing CD271+ MSCs could survive long term and engraft after intramuscular regeneration
	CXMDj transplanted with AAV1/IL-10-transduced hDPSCs	CXMDj transplanted with hDPSCs		Significantly higher torque was found in IL-10-hDPSC-treated CXMDj than in control CXMDj, which had similar values to hDPSC-treated CXMDj. hDPSC and IL-10-hDPSC-treated CXMDj maintained a 15-m running speed and were active at 3 to 12 months of age. Only IL-10-hDPSC was effective at reducing CK levels and lactic acid before and after exercise	Only IL-10-hDPSCs exert a protective effect against dystrophic damage caused by exercise
				IL-10-hDPSCs were only detected in the TA muscles and not in other organs. Dystrophin expression was undetectable in the muscle tissues of hDPSC-treated CXMDj
				Il-10-hDPSCs decreased inflammation and necrotic/edematous lesions and increased the weight and area of muscles. hDPSCs significantly limited the infiltration of nuclei, indicating a midler phenotype