TABLE 3.

Shows the diseases that have been studied using MSCs.

MSC sources	Diseases	Key findings	Key molecules	Signalling pathway involve	Animal model	References
Bone marrow mesenchymal stem cells (BM-MSCs)	Bronchiolitis obliterans	Three different administrations involve endotracheal (ET), intravenous (IV), or lung injection (LI). As BMSCs differentiate into alveolar cells, they modify bronchiolitis obliterans in a positive way. BMSC administration of BMSCs by endotracheal infusion 7 days after heterotopical tracheal transplant could be an effective way to prevent BO in this animal model	Surfactant protein B, which is a specific biomarker for alveolar epithelial cells	N/A	Wistar rats	Gómez de Antonio et al. (2020)
Adipose-derived mesenchymal stem cells (AD-MSCs)	Cognitive problems in Alzheimer’s disease	After intravenous transplantation, AD-MSCs and MT-AD-MSCs migrated to brain tissue. Pretreatment of AD-MSC with melatonin helps improve learning, memory, and cognition compared with AD-MSC.	Well-known anti-inflammatory and antioxidant agents Melatonin were used to pretreat AD-MSCs	MT exhibits a major ROS elimination potential, inhibits the p53 pathway, and regulates intracellular signaling	Wistar rats	Nasiri et al. (2019)
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs)	Retinal ischemia	In a rat model of retinal ischemia, administration 24 h after the event, increased functional recovery and neuroinflammation and apoptosis were decreased. In the retina, EVs were taken up by microglial cells, retinal ganglion cells, and neurons. A saturable binding to vitreous humor components was observed for 4 weeks after intravitreal administration. Reduce cell death and attenuated loss of cell proliferation	Caveolar endocytic pathway mediated by cell surface HSPG receptors	Caveolar pathways, phagocytosis, and macro-pinocytosis involved in endocytosis of EVs	Wistar rats	Mathew et al. (2019)
Exosomes derived from human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-ex)	Type 2 diabetes mellitus	Intravenous injection of hucMSC-ex reduced blood glucose levels. In T2DM, HucMSC-ex restored insulin receptor substrate 1 and protein kinase B phosphorylation (tyrosine site), increased muscle glucose transporter 4 expression, and increased liver glycogen storage to maintain glucose homeostasis by increasing glycogen storage. HucMSC-ex inhibits STZ-induced apoptosis, relieving T2DM of insulin-secreting functions	Insulin resistance is characterized by activation of protein kinase B (AKT) in patients with T2DM.	Insulin signaling pathway activation and IRS-1 tyrosine phosphorylation play key roles in glucose transport and metabolism	Sprague-Dawley (S-D) rats	Sun et al. (2018)
Exosomes derived from bone marrow mesenchymal stem cell derived exosomes (BMMSC-ex)	Bone regeneration	Cytokines and growth factors promote bone regeneration during the early stages, as well as enhanced angiogenesis. Histological analysis showed that in the MSC-Exo group, the newly formed bone area was larger than in the MSC-CM group	Growth factors such as insulin growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and transforming growth factor-1 (TGF-1) stimulate bone regeneration	MiRNAs enhance angiogenesis and osteogenesis	Wistar rats	Takeuchi et al. (2019)
Human endometrial mesenchymal stem cells (eMSCs)	Asherman’s syndrome (AS)	Rats modeled AS had significantly improved fertility when eMSCs were administered intrauterine in spheroids	Tumor necrosis factor-induced protein 6 (TSG-6) is an anti-inflammatory protein, while the hepatocyte growth factor (HGF) protein promotes angiogenesis and anti-apoptosis, and prostaglandin E receptor (EP2) interferes with immune stimulation	N/A	Wistar rats	Domnina et al. (2018)
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs)	Schizophrenia	MSC-EVs improve schizophrenia-like behaviour. MSC-EVs administered intranasally improve social interaction and disrupt prepulse inhibition (PPI) in mice treated with PCP. PCP-treated mice were found to have lower glutamate levels in their CSF when treated with MSC-EV, which may explain the reduced toxicity	Parvalbumin shows a decrease in schizophrenia mice at the level of prefrontal cortex (PFC) schizophrenia mice	N/A	C57Bl/6J mice	Tsivion-Visbord et al. (2020)
Human umbilical cord mesenchymal stem cells (hUC-MSCs)	Atherosclerosis	Reduces the burden of atherosclerotic plaques by reducing inflammation, regulating the intestinal flora, and repairing the damaged endothelium. With UCSC transplantation, the pathological inflammatory response was diminished by inhibiting cell apoptosis in susceptible plaques, reducing macrophages, and increasing anti-inflammatory cytokines. Transplantation of UCSCs improves peripheral blood vessel morphology and function during the early stage of AS.	Trimethylamine N-oxide (TMAO) is a microbial-dependent metabolite that increases the atherosclerosis lesion by increasing the expression of scavenger receptors	N/A	Rabbit	(Y. Li et al., 2021)
Embryonic stem cell-derived mesenchymal stem cell (ES-MSCs)	Osteoarthritis	Decelerates the progression of OA in a rat model, and multiple injections were required for long-term improvement	N/A	N/A	Sprague Dawley rats	Xing et al. (2021)
Human embryonic stem cell-derived mesenchymal stem cells (ES-MSCs)	Canine anal furunculosis	This is the first study to demonstrate the safety and potential therapeutic efficacy of hESC-MSCs in a large animal model. Intralesional injection of hESC-MSCs after 3 months and 6 months completes the fistula closing. Using this canine model, researchers can investigate the mechanisms of stem cell-derived therapies and evaluate how they are administered, dosage, frequency, and safety	IL-2 plays a key role in T cell activation/proliferation, so lowering circulating levels of this cytokine may reduce autoreactive T cell proliferation. IL-6 is one of the most common pleiotropic cytokines associated with inflammation and fistulas on human skin	N/A	Dogs	Ferrer et al. (2016)