Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes

Table 1

Summary of preclinical studies using MSCs to treat animals with diabetes mellitus.

Model/year	MSC sources	MSC dosage (cells)	Interventions	Effectiveness	References
HFD mice 2011	mBM-MSCs		Intravenous, single injection	Prevented the onset of nonalcoholic steatohepatitis in obese mice with metabolic syndromes	Ezquer et al. [18]
HFD mice 2014	rBM-MSCs	/g of body weight	Intravenous, single injection	Ameliorated diabetic hepatocyte damage by inhibiting infiltration of bone marrow-derived cells	Nagaishi et al. [25]
Fat-fed/STZ rat 2015	rBM-MSCs		Intravenous, single injection	Ameliorated chronic high glucose-induced β-cell injury through modulation of autophagy	Zhao et al. [22]
Fat-fed/STZ rat 2015	hUC-MSCs		Intravenous, single injection	Elicited macrophages into an anti-inflammatory phenotype to alleviate insulin resistance	Xie et al. [34]
HFD mice 2016	hAD-MSCs		Intraperitoneal, once every 2 weeks (up to 10 weeks)	Reduced obesity and metabolic syndromes	Lee et al. [17]
Fat-fed/STZ rat 2016	mAD-MSCs		Intravenous, single injection	Ameliorated hyperglycemia through regulating hepatic glucose metabolism	Xie et al. [24]
Fat-fed/STZ rat 2017	hUC-MSCs		Intravenous, single injection	Ameliorated insulin resistance by suppressing NLRP3 inflammasome-mediated inflammation	Sun et al. [35]
db/db mice; Fat-fed/STZ 2018	mAD-MSCs		Intravenous, single injection	Improved insulin sensitivity and less β-cell death seen in T2DM mice	Wang et al. [23]
Fat-fed/STZ rat 2018	hUC-MSCs	hUC-MSCs: Exosomes: 10 mg/kg	(1) Cell injection: intravenous, once every 2 weeks (up to 10 weeks); (2) Exosome injection: intravenous, once every 3 days for 5 cycles	Exosomes from hUC-MSCs could alleviate T2DM by reversing peripheral insulin resistance and relieving β-cell destruction	Sun et al. [20]
Fat-fed/STZ rat 2018	hUC-MSCs		Intravenous, single injection	Directed macrophage polarization to alleviate pancreatic islet dysfunction	Yin et al. [36]
db/db mice 2019	hUC-MSCs		Intravenous, once at 7 and 9 weeks of age	Reversed β-cell dedifferentiation in an IL-1Ra-mediated manner	Wang et al. [37]
HFD mice 2021	hAD-MSCs		Intravenous, once every 2 weeks (up to 1 month)	Achieved MSC self-augmentation, suppressed senescence and apoptosis of pancreatic β-cells, and decreased lipid accumulation in hepatocytes	Zhang et al. [30]

Abbreviations: BM-MSCs: bone marrow mesenchymal stem cells; UC-MSCs: umbilical cord mesenchymal stem cells; AD-MSCs: adipose-derived mesenchymal stem cells; STZ: streptozotocin; NLRP3: NOD-like receptor protein 3; IL-Ra: interleukin receptor agonist.